Functional Dependence for Calculation of Additional Real-Power Losses in a Double-Wound Supply Transformer Caused by Unbalanced Active Inductive Load in a Star Connection with an Insulated Neutral

ERIC Educational Resources Information Center

Kostinskiy, Sergey S.; Troitskiy, Anatoly I.

2016-01-01

This article deals with the problem of calculating the additional real-power losses in double-wound supply transformers with voltage class 6 (10)/0,4 kV, caused by unbalanced active inductive load connected in a star connection with an insulated neutral. When solving the problem, authors used the theory of electric circuits, method of balanced…

Non-expanded dispersion and induction energies, and damping functions, for molecular interactions with application to HF-He

NASA Astrophysics Data System (ADS)

Knowles, Peter J.; Meath, William J.

The evaluation of second order non-expanded dispersion and induction energies, and the associated damping functions, for interactions involving molecules is discussed with emphasis placed on using the time-dependent coupled Hartree-Fock method. Results are given for the HF-He interaction for all individual partial wave non-expanded dispersion and induction energies varying asymptotically for large R through O(R-8) and O(R-10) respectively and for most of the individual dispersion energies varying as R-9 and R-10. They are used to illustrate various features of charge overlap effects and the damping functions for molecular interactions, which are considerably more complicated than for atom-atom interactions.

Efficiency optimization of class-D biomedical inductive wireless power transfer systems by means of frequency adjustment.

PubMed

Schormans, Matthew; Valente, Virgilio; Demosthenous, Andreas

2015-01-01

Inductive powering for implanted medical devices is a commonly employed technique, that allows for implants to avoid more dangerous methods such as the use of transcutaneous wires or implanted batteries. However, wireless powering in this way also comes with a number of difficulties and conflicting requirements, which are often met by using designs based on compromise. In particular, one aspect common to most inductive power links is that they are driven with a fixed frequency, which may not be optimal depending on factors such as coupling and load. In this paper, a method is proposed in which an inductive power link is driven by a frequency that is maintained at an optimum value f(opt), to ensure that the link is in resonance. In order to maintain this resonance, a phase tracking technique is employed at the primary side of the link; this allows for compensation of changes in coil separation and load. The technique is shown to provide significant improvements in maintained secondary voltage and efficiency for a range of loads when the link is overcoupled.

Numerical investigation and electro-acoustic modeling of measurement methods for the in-duct acoustical source parameters.

PubMed

Jang, Seung-Ho; Ih, Jeong-Guon

2003-02-01

It is known that the direct method yields different results from the indirect (or load) method in measuring the in-duct acoustic source parameters of fluid machines. The load method usually comes up with a negative source resistance, although a fairly accurate prediction of radiated noise can be obtained from any method. This study is focused on the effect of the time-varying nature of fluid machines on the output results of two typical measurement methods. For this purpose, a simplified fluid machine consisting of a reservoir, a valve, and an exhaust pipe is considered as representing a typical periodic, time-varying system and the measurement situations are simulated by using the method of characteristics. The equivalent circuits for such simulations are also analyzed by considering the system as having a linear time-varying source. It is found that the results from the load method are quite sensitive to the change of cylinder pressure or valve profile, in contrast to those from the direct method. In the load method, the source admittance turns out to be predominantly dependent on the valve admittance at the calculation frequency as well as the valve and load admittances at other frequencies. In the direct method, however, the source resistance is always positive and the source admittance depends mainly upon the zeroth order of valve admittance.

High density growth of T7 expression strains with auto-induction option

DOEpatents

Studier, F William [Stony Brook, NY

2009-07-14

Disclosed is a method for promoting auto-induction of transcription of cloned DNA in cultures of bacterial cells grown batchwise, the transcription being under the control of a promoter whose activity can be induced by an exogenous inducer whose ability to induce said promoter is dependent on the metabolic state of said bacterial cells. Initially, a culture media is provided which includes: i) an inducer that causes induction of transcription from said promoter in said bacterial cells; and ii) a metabolite that prevents induction by said inducer, the concentration of said metabolite being adjusted so as to substantially preclude induction by said inducer in the early stages of growth of the bacterial culture, but such that said metabolite is depleted to a level that allows induction by said inducer at a later stage of growth. The culture medium is inoculated with a bacterial inoculum, the inoculum comprising bacterial cells containing cloned DNA, the transcription of which is induced by said inducer. The culture is then incubated under conditions appropriate for growth of the bacterial cells.

Introducing the Filtered Park's and Filtered Extended Park's Vector Approach to detect broken rotor bars in induction motors independently from the rotor slots number

NASA Astrophysics Data System (ADS)

Gyftakis, Konstantinos N.; Marques Cardoso, Antonio J.; Antonino-Daviu, Jose A.

2017-09-01

The Park's Vector Approach (PVA), together with its variations, has been one of the most widespread diagnostic methods for electrical machines and drives. Regarding the broken rotor bars fault diagnosis in induction motors, the common practice is to rely on the width increase of the Park's Vector (PV) ring and then apply some more sophisticated signal processing methods. It is shown in this paper that this method can be unreliable and is strongly dependent on the magnetic poles and rotor slot numbers. To overcome this constraint, the novel Filtered Park's/Extended Park's Vector Approach (FPVA/FEPVA) is introduced. The investigation is carried out with FEM simulations and experimental testing. The results prove to satisfyingly coincide, whereas the proposed advanced FPVA method is desirably reliable.

Superconducting-electromagnetic hybrid bearing using YBCO bulk blocks for passive axial levitation

NASA Astrophysics Data System (ADS)

Nicolsky, R.; de Andrade, R., Jr.; Ripper, A.; David, D. F. B.; Santisteban, J. A.; Stephan, R. M.; Gawalek, W.; Habisreuther, T.; Strasser, T.

2000-06-01

A superconducting/electromagnetic hybrid bearing has been designed using active radial electromagnetic positioning and a superconducting passive axial levitator. This bearing has been tested for an induction machine with a vertical shaft. The prototype was conceived as a four-pole, two-phase induction machine using specially designed stator windings for delivering torque and radial positioning simultaneously. The radial bearing uses four eddy-current sensors, displaced 90° from each other, for measuring the shaft position and a PID control system for feeding back the currents. The stator windings have been adapted from the ones of a standard induction motor. The superconducting axial bearing has been assembled with commercial NdFeB permanent magnets and a set of seven top-seeded-melt-textured YBCO large-grain cylindrical blocks. The bearing set-up was previously simulated by a finite element method for different permanent magnet-superconductor block configurations. The stiffness of the superconducting axial bearing has been investigated by measuring by a dynamic method the vertical and transversal elastic constants for different field cooling processes. The resulting elastic constants show a linear dependence on the air gap, i.e. the clearance between the permanent magnet assembly and the set of superconducting large-grain blocks, which is dependent on cooling distance.

[Criteria for the determination of the distance of a gunshot from limited-range firearms based on the morphological characteristics of the wound and the results of inductively coupled plasma mass spectrometry].

PubMed

Svetlolobov, D Iu; Luzanova, I S; Demidov, I V; Zorin, Iu V; Sonis, M A; Likhachev, A S

2013-01-01

We have developed the criteria allowing to determine the distance of a gunshot from limited-range firearms (an IZh-79-9TGM pistol with the elastic bullet cartridges) based on the morphological characteristics of the wound and the results of inductively coupled plasma mass spectrometry. The method has been developed for the quantitative determination of barium, lead, and antimony in the targets depending on the gunshot distance.

Hexavalent Chromium Cr(VI) Up-Regulates COX-2 Expression through an NFκB/c-Jun/AP-1–Dependent Pathway

PubMed Central

Zuo, Zhenghong; Cai, Tongjian; Li, Jingxia; Zhang, Dongyun; Yu, Yonghui

2012-01-01

Background: Hexavalent chromium [Cr(VI)] is recognized as a human carcinogen via inhalation. However, the molecular mechanisms by which Cr(VI) causes cancers are not well understood. Objectives: We evaluated cyclooxygenase-2 (COX-2) expression and the signaling pathway leading to this induction due to Cr(VI) exposure in cultured cells. Methods: We used the luciferase reporter assay and Western blotting to determine COX-2 induction by Cr(VI). We used dominant negative mutant, genetic knockout, gene knockdown, and chromatin immunoprecipitation approaches to elucidate the signaling pathway leading to COX-2 induction. Results: We found that Cr(VI) exposure induced COX-2 expression in both normal human bronchial epithelial cells and mouse embryonic fibroblasts in a concentration- and time-dependent manner. Deletion of IKKβ [inhibitor of transcription factor NFκB (IκB) kinase β; an upstream kinase responsible for nuclear factor κB (NFκB) activation] or overexpression of TAM67 (a dominant-negative mutant of c-Jun) dramatically inhibited the COX-2 induction due to Cr(VI), suggesting that both NFκB and c-Jun/AP-1 pathways were required for Cr(VI)-induced COX-2 expression. Our results show that p65 and c-Jun are two major components involved in NFκB and AP-1 activation, respectively. Moreover, our studies suggest crosstalk between NFκB and c-Jun/AP-1 pathways in cellular response to Cr(VI) exposure for COX-2 induction. Conclusion: We demonstrate for the first time that Cr(VI) is able to induce COX-2 expression via an NFκB/c-Jun/AP-1–dependent pathway. Our results provide novel insight into the molecular mechanisms linking Cr(VI) exposure to lung inflammation and carcinogenesis. PMID:22472290

Induction hardening treatment and simulation for a grey cast iron used in engine cylinder liners

NASA Astrophysics Data System (ADS)

Castellanos-Leal, E. L.; Miranda, D. A.; Coy, A. E.; Barrero, J. G.; González, J. A.; Vesga Rueda, O. P.

2017-01-01

In this research, a technical study of induction hardening in a grey cast iron used in engine cylinder liners manufactured by LAVCO Ltda., a Colombian foundry company, was carried out. Metallurgical parameters such as austenitization temperature, cooling rate, and quenching severity were determined. These factors are exclusively dependent on chemical composition and initial microstructure of grey cast iron. Simulations of induction heating through finite elements method were performed and, the most appropriate experimental conditions to achieve the critical transformation temperature was evaluated to reach a proper surface hardening on the piece. Preliminary results revealed an excellent approximation between simulation and heating test performed with a full bridge inverter voltage adapted with local technology.

The Mechanism of Autoinduction of Methadone N-demethylation in Human Hepatocytes

PubMed Central

Campbell, Scott D.; Crafford, Amanda; Williamson, Brian L.; Kharasch, Evan D.

2013-01-01

Background There is considerable inter-and intraindividual variability in methadone metabolism and clearance. Methadone dosing is particularly challenging during initiation of therapy, due to time-dependent increases in hepatic clearance (autoinduction). Although methadone N-demethylation is catalyzed in vitro by cytochrome P4502B6 (CYP2B6) and CYP3A4, and clearance in vivo depends on CYP2B6, mechanism(s) of autoinduction are incompletely understood. In this investigation we determined mechanism(s) of methadone autoinduction using human hepatocytes. Methods Fresh human hepatocytes were exposed to 0.1-10 μM methadone for 72 hr. Cells were washed and methadone N-demethylation assessed. CYP2B6, CYP3A4, and CYP3A5 mRNA, protein expression (by gel-free high performance liquid chromatography-mass spectrometry) and catalytic activity (bupropion hydroxylation and alfentanil dealkylation for CYP2B6 and CYP3A4/5, respectively) were measured. Mechanisms of CYP induction were characterized using pregnane X receptor and constitutive androstane receptor reporter gene assays. Results Methadone (10 μM) increased methadone N-demethylation 2-fold, CYP2B6 and CYP3A4 mRNA 3-fold, and protein expression 2-fold. CYP3A5 mRNA was unchanged. CYP2B6 and CYP3A4/5 activities increased 2-fold. Induction by methadone enantiomers (R- vs S-methadone) did not differ. Induction was relatively weak compared with maximum induction by phenobarbital and rifampin. Lower methadone concentrations had smaller effects. Methadone was an agonist for the pregnane X receptor but not the constitutive androstane receptor. Conclusions Methadone caused concentration-dependent autoinduction of methadone N-demethylation in human hepatocytes, related to induction of CYP2B6 and CYP3A4 mRNA expression, protein expression, and catalytic activity. Induction was related to pregnane X receptor but not constitutive androstane receptor activation. These in vitro findings provide mechanistic insights into clinical autoinduction of methadone metabolism and clearance. PMID:23733841

Comparative study of two commercially pure titanium casting methods

PubMed Central

RODRIGUES, Renata Cristina Silveira; FARIA, Adriana Claudia Lapria; ORSI, Iara Augusta; de MATTOS, Maria da Gloria Chiarello; MACEDO, Ana Paula; RIBEIRO, Ricardo Faria

2010-01-01

The interest in using titanium to fabricate removable partial denture (RPD) frameworks has increased, but there are few studies evaluating the effects of casting methods on clasp behavior. Objective This study compared the occurrence of porosities and the retentive force of commercially pure titanium (CP Ti) and cobalt-chromium (Co-Cr) removable partial denture circumferential clasps cast by induction/centrifugation and plasma/vacuum-pressure. Material and Methods 72 frameworks were cast from CP Ti (n=36) and Co-Cr alloy (n=36; control group). For each material, 18 frameworks were casted by electromagnetic induction and injected by centrifugation, whereas the other 18 were casted by plasma and injected by vacuum-pressure. For each casting method, three subgroups (n=6) were formed: 0.25 mm, 0.50 mm, and 0.75 mm undercuts. The specimens were radiographed and subjected to an insertion/removal test simulating 5 years of framework use. Data were analyzed by ANOVA and Tukey's to compare materials and cast methods (α=0.05). Results Three of 18 specimens of the induction/centrifugation group and 9 of 18 specimens of plasma/vacuum-pressure cast presented porosities, but only 1 and 7 specimens, respectively, were rejected for simulation test. For Co-Cr alloy, no defects were found. Comparing the casting methods, statistically significant differences (p<0.05) were observed only for the Co-Cr alloy with 0.25 mm and 0.50 mm undercuts. Significant differences were found for the 0.25 mm and 0.75 mm undercuts dependent on the material used. For the 0.50 mm undercut, significant differences were found when the materials were induction casted. Conclusion Although both casting methods produced satisfactory CP Ti RPD frameworks, the occurrence of porosities was greater in the plasma/vacuum-pressure than in the induction/centrifugation method, the latter resulting in higher clasp rigidity, generating higher retention force values. PMID:21085805

Enhanced thyroid hormone breakdown in hepatocytes by mutual induction of the constitutive androstane receptor (CAR, NR1I3) and arylhydrocarbon receptor by benzo[a]pyrene and phenobarbital.

PubMed

Schraplau, Anne; Schewe, Bettina; Neuschäfer-Rube, Frank; Ringel, Sebastian; Neuber, Corinna; Kleuser, Burkhard; Püschel, Gerhard P

2015-02-03

Xenobiotics may interfere with the hypothalamic-pituitary-thyroid endocrine axis by inducing enzymes that inactivate thyroid hormones and thereby reduce the metabolic rate. This induction results from an activation of xeno-sensing nuclear receptors. The current study shows that benzo[a]pyrene, a frequent contaminant of processed food and activator of the arylhydrocarbon receptor (AhR) activated the promoter and induced the transcription of the nuclear receptor constitutive androstane receptor (CAR, NR1I3) in rat hepatocytes. Likewise, phenobarbital induced the AhR transcription. This mutual induction of the nuclear receptors enhanced the phenobarbital-dependent induction of the prototypic CAR target gene Cyp2b1 as well as the AhR-dependent induction of UDP-glucuronosyltransferases. In both cases, the induction by the combination of both xenobiotics was more than the sum of the induction by either substance alone. By inducing the AhR, phenobarbital enhanced the benzo[a]pyrene-dependent reduction of thyroid hormone half-life and the benzo[a]pyrene-dependent increase in the rate of thyroid hormone glucuronide formation in hepatocyte cultures. CAR ligands might thus augment the endocrine disrupting potential of AhR activators by an induction of the AhR. Copyright © 2014. Published by Elsevier Ireland Ltd.

The Influence of a High Salt Diet on a Rat Model of Isoproterenol-Induced Heart Failure

EPA Science Inventory

Rat models of heart failure (HF) show varied pathology and time to disease outcome, dependent on induction method. We found that subchronic (4 weeks) isoproterenol (ISO) infusion exacerbated cardiomyopathy in Spontaneously Hypertensive Heart Failure (SHHF) rats. Others have shown...

A RAT MODEL OF HEART FAILURE INDUCED BY ISOPROTERENOL AND A HIGH SALT DIET

EPA Science Inventory

Rat models of heart failure (HF) show varied pathology and time to disease outcome, dependent on induction method. We found that subchronic (4wk) isoproterenol (ISO) infusion in Spontaneously Hypertensive Heart Failure (SHHF) rats caused cardiac injury with minimal hypertrophy. O...

FRACTIONAL AEROSOL FILTRATION EFFICIENCY OF IN-DUCT VENTILATION AIR CLEANERS

EPA Science Inventory

The filtration efficiency of ventilation air cleaners is highly particle-size dependent over the 0.01 to 3 μm diameter size range. Current standardized test methods, which determine only overall efficiencies for ambient aerosol or other test aerosols, provide data of limited util...

Penetration depth of MgB2 measured using Josephson junctions and SQUIDs

NASA Astrophysics Data System (ADS)

Cunnane, Daniel; Zhuang, Chenggang; Chen, Ke; Xi, X. X.; Yong, Jie; Lemberger, T. R.

2013-02-01

The penetration depth of MgB2 was measured using two methods of different mechanisms. The first method used MgB2 Josephson junctions and the magnetic field dependence of the junction critical current. The second method deduced the penetration depth from the inductance of a MgB2 microstrip used to modulate the voltage of a MgB2 DC SQUID. The two methods showed a consistent value of the low-temperature penetration depth for MgB2 to be about 40 nm. Both the small penetration depth value and its temperature dependence are in agreement with a microscopic theory for MgB2 in the clean limit.

Multivariate analysis of flow cytometric data using decision trees.

PubMed

Simon, Svenja; Guthke, Reinhard; Kamradt, Thomas; Frey, Oliver

2012-01-01

Characterization of the response of the host immune system is important in understanding the bidirectional interactions between the host and microbial pathogens. For research on the host site, flow cytometry has become one of the major tools in immunology. Advances in technology and reagents allow now the simultaneous assessment of multiple markers on a single cell level generating multidimensional data sets that require multivariate statistical analysis. We explored the explanatory power of the supervised machine learning method called "induction of decision trees" in flow cytometric data. In order to examine whether the production of a certain cytokine is depended on other cytokines, datasets from intracellular staining for six cytokines with complex patterns of co-expression were analyzed by induction of decision trees. After weighting the data according to their class probabilities, we created a total of 13,392 different decision trees for each given cytokine with different parameter settings. For a more realistic estimation of the decision trees' quality, we used stratified fivefold cross validation and chose the "best" tree according to a combination of different quality criteria. While some of the decision trees reflected previously known co-expression patterns, we found that the expression of some cytokines was not only dependent on the co-expression of others per se, but was also dependent on the intensity of expression. Thus, for the first time we successfully used induction of decision trees for the analysis of high dimensional flow cytometric data and demonstrated the feasibility of this method to reveal structural patterns in such data sets.

Comparison of analytical performances of inductively coupled plasma mass spectrometry and inductively coupled plasma atomic emission spectrometry for trace analysis of bismuth and bismuth oxide

NASA Astrophysics Data System (ADS)

Medvedev, Nickolay S.; Shaverina, Anastasiya V.; Tsygankova, Alphiya R.; Saprykin, Anatoly I.

2018-04-01

The paper presents а comparison of analytical performances of inductively coupled plasma mass spectrometry (ICP-MS) and inductively coupled plasma atomic emission spectrometry (ICP-AES) for trace analysis of high purity bismuth and bismuth oxide. Matrix effects in the ICP-MS and ICP-AES methods were studied as a function of Bi concentration, ICP power and nebulizer flow rate. For ICP-MS the strong dependence of the matrix effects versus the atomic mass of analytes was observed. For ICP-AES the minimal matrix effects were achieved for spectral lines of analytes with low excitation potentials. The optimum degree of sample dilution providing minimum values of the limits of detection (LODs) was chosen. Both methods let us to reach LODs from n·10-7 to n·10-4 wt% for more than 50 trace elements. For most elements the LODs of ICP-MS were lower in comparison to ICP-AES. Validation of accuracy of the developed techniques was performed by "added-found" experiments and by comparison of the results of ICP-MS and ICP-AES analysis of high-purity bismuth oxide.

Development, awareness and inductive selectivity.

PubMed

Hayes, Brett K; Lim, Melissa

2013-05-01

Two studies examined whether adults and children could learn to make context-dependent inferences about novel stimuli and the role of awareness of context cues in such learning. Participants were trained to match probes to targets on the basis of shape or color with the relevant dimension shifting according to item context. A selective induction test then examined context-dependent responding in a more complex matching task. Awareness of the role of context was assessed using a behavioral task and explicit questions. Experiment 1 showed that after training with the procedure described by Sloutsky and Fisher (2008), only a minority of adults showed evidence of context-dependent responding in the selective induction test. Experiment 2 used a modified training protocol that promoted attention to context cues. This led to reliable selective induction in a majority of adults and a sizeable proportion of 4- to 6-year-olds. Crucially, in both age groups, selective induction was dependent on awareness of context. Hence, children as young as 4 can learn to make selective inferences about novel stimuli, but only when they are aware of the relevant context cues. These results challenge previous claims that selective induction in children is the product of implicit learning.

Approximate analytical solution for induction heating of solid cylinders

DOE PAGES

Jankowski, Todd Andrew; Pawley, Norma Helen; Gonzales, Lindsey Michal; ...

2015-10-20

An approximate solution to the mathematical model for induction heating of a solid cylinder in a cylindrical induction coil is presented here. The coupled multiphysics model includes equations describing the electromagnetic field in the heated object, a heat transfer simulation to determine temperature of the heated object, and an AC circuit simulation of the induction heating power supply. A multiple-scale perturbation method is used to solve the multiphysics model. The approximate analytical solution yields simple closed-form expressions for the electromagnetic field and heat generation rate in the solid cylinder, for the equivalent impedance of the associated tank circuit, and formore » the frequency response of a variable frequency power supply driving the tank circuit. The solution developed here is validated by comparing predicted power supply frequency to both experimental measurements and calculated values from finite element analysis for heating of graphite cylinders in an induction furnace. The simple expressions from the analytical solution clearly show the functional dependence of the power supply frequency on the material properties of the load and the geometrical characteristics of the furnace installation. In conclusion, the expressions developed here provide physical insight into observations made during load signature analysis of induction heating.« less

Effects of Vegetable Oil Type and Lipophilic Emulsifiers on the Induction Period of Fat Crystallization.

PubMed

Miyagawa, Yayoi; Ogawa, Takenobu; Nakagawa, Kyuya; Adachi, Shuji

2015-01-01

The induction period of crystallization, which is defined as the time required for oil to start to crystallize, is useful indicator of the freeze-thaw stability of food emulsions such as mayonnaise. We investigated the induction period of vegetable oils with low melting points, such as rapeseed and soybean oils, which are commonly employed for mayonnaise production. The induction period was measured by monitoring the temperature of a specimen during storage at low temperature. The induction period depended on the type of oil and lipophilic emulsifier, emulsifier concentration, and storage temperature. The effect of the oil type on the induction period depended on the composition of the oil. Differential scanning calorimetry (DSC) analyses of the lipophilic emulsifiers suggested that the melting trend of the emulsifier is strongly related to the induction period.

Zebrafish Foxi1 provides a neuronal ground state during inner ear induction preceding the Dlx3b/4b-regulated sensory lineage.

PubMed

Hans, Stefan; Irmscher, Anne; Brand, Michael

2013-05-01

Vertebrate inner ear development is a complex process that involves the induction of a common territory for otic and epibranchial precursors and their subsequent segregation into otic and epibranchial cell fates. In zebrafish, the otic-epibranchial progenitor domain (OEPD) is induced by Fgf signaling in a Foxi1- and Dlx3b/4b-dependent manner, but the functional differences of Foxi1 and Dlx3b/4b in subsequent cell fate specifications within the developing inner ear are poorly understood. Based on pioneer tracking (PioTrack), a novel Cre-dependent genetic lineage tracing method, and genetic data, we show that the competence to embark on a neuronal or sensory fate is provided sequentially and very early during otic placode induction. Loss of Foxi1 prevents neuronal precursor formation without affecting hair cell specification, whereas loss of Dlx3b/4b inhibits hair cell but not neuronal precursor formation. Consistently, in Dlx3b/4b- and Sox9a-deficient b380 mutants almost all otic epithelial fates are absent, including sensory hair cells, and the remaining otic cells adopt a neuronal fate. Furthermore, the progenitors of the anterior lateral line ganglia also arise from the OEPD in a Foxi1-dependent manner but are unaffected in the absence of Dlx3b/4b or in b380 mutants. Thus, in addition to otic fate Foxi1 provides neuronal competence during OEPD induction prior to and independently of the Dlx3b/4b-mediated sensory fate of the developing inner ear.

Relations among Categorization, Induction, Recognition, and Similarity: Comment on Sloutsky and Fisher (2004)

ERIC Educational Resources Information Center

Heit, Evan; Hayes, Brett K.

2005-01-01

V. M. Sloutsky and A. V. Fisher reported 5 experiments documenting relations among categorization, induction, recognition, and similarity in children as well as adults and proposed a new model of induction, SINC (similarity, induction, categorization). Those authors concluded that induction depends on perceptual similarity rather than conceptual…

The use of nutritional supplements to induce ketosis and reduce symptoms associated with keto-induction: a narrative review

PubMed Central

Schofield, Grant M.; Williden, Micalla

2018-01-01

Background Adaptation to a ketogenic diet (keto-induction) can cause unpleasant symptoms, and this can reduce tolerability of the diet. Several methods have been suggested as useful for encouraging entry into nutritional ketosis (NK) and reducing symptoms of keto-induction. This paper reviews the scientific literature on the effects of these methods on time-to-NK and on symptoms during the keto-induction phase. Methods PubMed, Science Direct, CINAHL, MEDLINE, Alt Health Watch, Food Science Source and EBSCO Psychology and Behavioural Sciences Collection electronic databases were searched online. Various purported ketogenic supplements were searched along with the terms “ketogenic diet”, “ketogenic”, “ketosis” and ketonaemia (/ ketonemia). Additionally, author names and reference lists were used for further search of the selected papers for related references. Results Evidence, from one mouse study, suggests that leucine doesn’t significantly increase beta-hydroxybutyrate (BOHB) but the addition of leucine to a ketogenic diet in humans, while increasing the protein-to-fat ratio of the diet, doesn’t reduce ketosis. Animal studies indicate that the short chain fatty acids acetic acid and butyric acid, increase ketone body concentrations. However, only one study has been performed in humans. This demonstrated that butyric acid is more ketogenic than either leucine or an 8-chain monoglyceride. Medium-chain triglycerides (MCTs) increase BOHB in a linear, dose-dependent manner, and promote both ketonaemia and ketogenesis. Exogenous ketones promote ketonaemia but may inhibit ketogenesis. Conclusions There is a clear ketogenic effect of supplemental MCTs; however, it is unclear whether they independently improve time to NK and reduce symptoms of keto-induction. There is limited research on the potential for other supplements to improve time to NK and reduce symptoms of keto-induction. Few studies have specifically evaluated symptoms and adverse effects of a ketogenic diet during the induction phase. Those that have typically were not designed to evaluate these variables as primary outcomes, and thus, more research is required to elucidate the role that supplementation might play in encouraging ketogenesis, improve time to NK, and reduce symptoms associated with keto-induction. PMID:29576959

Induction of MAPK- and ROS-dependent autophagy and apoptosis in gastric carcinoma by combination of romidepsin and bortezomib

PubMed Central

Hui, Kwai Fung; Yeung, Po Ling; Chiang, Alan K.S.

2016-01-01

Proteasome inhibitors and histone deacetylase (HDAC) inhibitors can synergistically induce apoptotic cell death in certain cancer cell types but their combinatorial effect on the induction of autophagy remains unknown. Here, we investigated the combinatorial effects of a proteasome inhibitor, bortezomib, and an HDAC inhibitor, romidepsin, on the induction of apoptotic and autophagic cell death in gastric carcinoma (GC) cells. Isobologram analysis showed that low nanomolar concentrations of bortezomib/romidepsin could synergistically induce killing of GC cells. The synergistic killing was due to the summative effect of caspase-dependent intrinsic apoptosis and caspase-independent autophagy. The autophagic cell death was dependent on the activation of MAPK family members (ERK1/2 and JNK), and generation of reactive oxygen species (ROS), but was independent of Epstein-Barr virus infection. In vivo, bortezomib/romidepsin also significantly induced apoptosis and autophagy in GC xenografts in nude mice. This is the first report demonstrating the potent effect of combination of HDAC and proteasome inhibitors on the induction of MAPK- and ROS-dependent autophagy in addition to caspase-dependent apoptosis in a cancer type. PMID:26683357

Induction of MAPK- and ROS-dependent autophagy and apoptosis in gastric carcinoma by combination of romidepsin and bortezomib.

PubMed

Hui, Kwai Fung; Yeung, Po Ling; Chiang, Alan K S

2016-01-26

Proteasome inhibitors and histone deacetylase (HDAC) inhibitors can synergistically induce apoptotic cell death in certain cancer cell types but their combinatorial effect on the induction of autophagy remains unknown. Here, we investigated the combinatorial effects of a proteasome inhibitor, bortezomib, and an HDAC inhibitor, romidepsin, on the induction of apoptotic and autophagic cell death in gastric carcinoma (GC) cells. Isobologram analysis showed that low nanomolar concentrations of bortezomib/romidepsin could synergistically induce killing of GC cells. The synergistic killing was due to the summative effect of caspase-dependent intrinsic apoptosis and caspase-independent autophagy. The autophagic cell death was dependent on the activation of MAPK family members (ERK1/2 and JNK), and generation of reactive oxygen species (ROS), but was independent of Epstein-Barr virus infection. In vivo, bortezomib/romidepsin also significantly induced apoptosis and autophagy in GC xenografts in nude mice. This is the first report demonstrating the potent effect of combination of HDAC and proteasome inhibitors on the induction of MAPK- and ROS-dependent autophagy in addition to caspase-dependent apoptosis in a cancer type.

MRAS state estimator for speed sensorless ISFOC induction motor drives with Luenberger load torque estimation.

PubMed

Zorgani, Youssef Agrebi; Koubaa, Yassine; Boussak, Mohamed

2016-03-01

This paper presents a novel method for estimating the load torque of a sensorless indirect stator flux oriented controlled (ISFOC) induction motor drive based on the model reference adaptive system (MRAS) scheme. As a matter of fact, this method is meant to inter-connect a speed estimator with the load torque observer. For this purpose, a MRAS has been applied to estimate the rotor speed with tuned load torque in order to obtain a high performance ISFOC induction motor drive. The reference and adjustable models, developed in the stationary stator reference frame, are used in the MRAS scheme in an attempt to estimate the speed of the measured terminal voltages and currents. The load torque is estimated by means of a Luenberger observer defined throughout the mechanical equation. Every observer state matrix depends on the mechanical characteristics of the machine taking into account the vicious friction coefficient and inertia moment. Accordingly, some simulation results are presented to validate the proposed method and to highlight the influence of the variation of the inertia moment and the friction coefficient on the speed and the estimated load torque. The experimental results, concerning to the sensorless speed with a load torque estimation, are elaborated in order to validate the effectiveness of the proposed method. The complete sensorless ISFOC with load torque estimation is successfully implemented in real time using a digital signal processor board DSpace DS1104 for a laboratory 3 kW induction motor. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

Controlling hollow relativistic electron beam orbits with an inductive current divider

DOE PAGES

Swanekamp, S. B.; Richardson, A. S.; Angus, J. R.; ...

2015-02-06

A passive method for controlling the trajectory of an intense, hollow electron beam is proposed using a vacuum structure that inductively splits the beam's return current. A central post carries a portion of the return current (I 1), while the outer conductor carries the remainder (I 2). An envelope equation appropriate for a hollow electron beam is derived and applied to the current divider. The force on the beam trajectory is shown to be proportional to (I 2-I 1), while the average force on the envelope (the beam width) is proportional to the beam current I b = (I 2more » + I 1). The values of I 1 and I 2 depend on the inductances in the return-current path geometries. Proper choice of the return-current geometries determines these inductances and offers control over the beam trajectory. As a result, solutions using realistic beam parameters show that, for appropriate choices of the return-current-path geometry, the inductive current divider can produce a beam that is both pinched and straightened so that it approaches a target at near-normal incidence with a beam diameter that is on the order of a few mm.« less

Evaluation of inductively heated ferromagnetic alloy implants for therapeutic interstitial hyperthermia.

PubMed

Paulus, J A; Richardson, J S; Tucker, R D; Park, J B

1996-04-01

Ferromagnetic alloys heated by magnetic induction have been investigated as interstitial hyperthermia delivery implants for over a decade, utilizing low Curie temperatures to provide thermal self-regulation. The minimally invasive method is attractive for fractionated thermal treatment of tumors which are not easily heated by focused microwave or ultrasound techniques. Past analyses of ferromagnetic seeds by other authors depict poor experimental correlation with theoretical heating predictions. Improvements in computer hardware and commercially available finite element analysis software have simplified the analysis of inductively heated thermal seeds considerably. This manuscript examines end effects of finite length implants and nonlinear magnetic material properties to account for previous inconsistencies. Two alloys, Ni-28 wt% Cu (NiCu) and Pd-6.15 wt% Co (PdCo), were used for comparison of theoretical and experimental calorimetric results. Length to diameter (L/d) ratios of over 20 for cylindrical seeds are necessary for minimization of end effects. Magnetic properties tested for alloys of NiCu and PdCo illustrate considerable nonlinearity of these materials in field strength ranges used for induction heating. Field strength dependent magnetic permeabilities and calorimetric data illustrate that more detailed material information must be included to accurately estimate induction power loss for these implants.

Geometric Model of Induction Heating Process of Iron-Based Sintered Materials

NASA Astrophysics Data System (ADS)

Semagina, Yu V.; Egorova, M. A.

2018-03-01

The article studies the issue of building multivariable dependences based on the experimental data. A constructive method for solving the issue is presented in the form of equations of (n-1) – surface compartments of the extended Euclidean space E+n. The dimension of space is taken to be equal to the sum of the number of parameters and factors of the model of the system being studied. The basis for building multivariable dependencies is the generalized approach to n-space used for the surface compartments of 3D space. The surface is designed on the basis of the kinematic method, moving one geometric object along a certain trajectory. The proposed approach simplifies the process aimed at building the multifactorial empirical dependencies which describe the process being investigated.

A review and comparison of fault detection and diagnosis methods for squirrel-cage induction motors: State of the art.

PubMed

Liu, Yiqi; Bazzi, Ali M

2017-09-01

Preventing induction motors (IMs) from failure and shutdown is important to maintain functionality of many critical loads in industry and commerce. This paper provides a comprehensive review of fault detection and diagnosis (FDD) methods targeting all the four major types of faults in IMs. Popular FDD methods published up to 2010 are briefly introduced, while the focus of the review is laid on the state-of-the-art FDD techniques after 2010, i.e. in 2011-2015 and some in 2016. Different FDD methods are introduced and classified into four categories depending on their application domains, instead of on fault types like in many other reviews, to better reveal hidden connections and similarities of different FDD methods. Detailed comparisons of the reviewed papers after 2010 are given in tables for fast referring. Finally, a dedicated discussion session is provided, which presents recent developments, trends and remaining difficulties regarding to FDD of IMs, to inspire novel research ideas and new research possibilities. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

Functionally different α-synuclein inclusions yield insight into Parkinson’s disease pathology

PubMed Central

Raiss, Christian C.; Braun, Theresa S.; Konings, Irene B. M.; Grabmayr, Heinrich; Hassink, Gerco C.; Sidhu, Arshdeep; le Feber, Joost; Bausch, Andreas R.; Jansen, Casper; Subramaniam, Vinod; Claessens, Mireille M. A. E.

2016-01-01

The formation of α-synuclein (α-S) amyloid aggregates, called Lewy bodies (LBs), is a hallmark of Parkinson’s disease (PD). The function of LBs in the disease process is however still unclear; they have been associated with both neuroprotection and toxicity. To obtain insight into this contradiction, we induced the formation of α-S inclusions, using three different induction methods in SH-SY5Y cells and rat-derived primary neuronal cells. Using confocal and STED microscopy we observed induction-dependent differences in α-S inclusion morphology, location and function. The aggregation of α-S in functionally different compartments correlates with the toxicity of the induction method measured in viability assays. The most cytotoxic treatment largely correlates with the formation of proteasome-associated, juxta-nuclear inclusions. With less toxic methods cytosolic deposits that are not associated with the proteasome are more prevalent. The distribution of α-S over at least two different types of inclusions is not limited to cell models, but is also observed in primary neuronal cells and in human mesencephalon. The existence of functionally different LBs, in vivo and in vitro, gives important insights in the impact of Lewy Body formation on neuronal functioning and may thereby provide a platform for discovering therapeutics. PMID:26984067

Induction of Apoptosis and Nonsteroidal Antiinflammatory Drug-Activated Gene 1 in Pancreatic Cancer Cells By A Glycyrrhetinic Acid Derivative

PubMed Central

Jutooru, Indira; Chadalapaka, Gayathri; Chintharlapalli, Sudhakar; Papineni, Sabitha; Safe, Stephen

2009-01-01

Methyl 2-cyano-3,11-dioxo-18β-olean-1,12-dien-30-oate (CDODA-Me) is a synthetic triterpenoid derived from glycyrrhetinic acid, a bioactive phytochemical in licorice, CDODA-Me inhibits growth of Panc1 and Panc28 pancreatic cancer cell lines and activates peroxisome proliferator-activated receptor γ (PPARγ)-dependent transactivation in these cells. CDODA-Me also induced p21 and p27 protein expression and downregulates cyclin D1; however, these responses were receptor-independent. CDODA-Me induced apoptosis in Panc1 and Panc28 cells, and this was accompanied by receptor-independent induction of the proapoptotic proteins early growth response-1 (Egr-1), nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1), and activating transcription factor-3 (ATF3). Induction of NAG-1 and Egr-1 by CDODA-Me was dependent on activation of phosphatidylinositol-3-kinase (PI3-K) and/or p42 and p38 mitogen-activated protein kinase (MAPK) pathways but there were differences between Panc28 and Panc1 cells. Induction of NAG-1 in Panc28 cells was p38-MAPK- and PI3-K-dependent but Egr-1-independent, whereas induction in Panc1 cells was associated with activation of p38-MAPK, PI3-K and p42-MAPK and was only partially Egr-1-dependent. This is the first report of the induction of the proapoptotic protein NAG-1 in pancreatic cancer cells. PMID:19125423

Definition of Time Induction of Self-Ignition of the Substance on the Prognostic Extrapolation Depending on the Basis of Indicators Fire and Explosion Hazard

NASA Astrophysics Data System (ADS)

Sechin, A.; Kyrmakova, O.; Osipenko, S.

2016-01-01

In this article the research directed on development of a technique of definition of time of induction of the self-ignition of substances and materials which is an indicator of the beginning of development of an emergency is conducted. The experiment consisting in supervision over process of self-ignition of coal and oil deposits was the basis for research. On the basis of experimental data the curve expressing analytic - expected dependence of size of temperature of ignition on induction time was constructed. Proceeding from graphical representation of process, functional dependence of time of induction on a temperature indicator was received: y = 16920 • x0 537. By means of known indicators of such substances as bitumen oil oxidized (the combustible solid substance received by oxidation of residual product of oil refining) and tar oil (the combustible solid substance which is residual product of oil refining) and the received algorithm, verification of reliability of the received dependence and a technique of definition of time of induction of spontaneous ignition of deposits of oil in general was carried out. The practical importance of the conducted research is that having data on time of induction of process of self-ignition, by means of preventive measures becomes possible to avoid and prevent accidents in oil and oil processing branches, at the same time loss of property and loss of human life.

Short-term regulation and alternative pathways of photosynthetic electron transport in Hibiscus rosa-sinensis leaves.

PubMed

Trubitsin, Boris V; Vershubskii, Alexey V; Priklonskii, Vladimir I; Tikhonov, Alexander N

2015-11-01

In this work, using the EPR and PAM-fluorometry methods, we have studied induction events of photosynthetic electron transport in Hibiscus rosa-sinensis leaves. The methods used are complementary, providing efficient tools for in situ monitoring of P700 redox transients and photochemical activity of photosystem II (PSII). The induction of P700(+) in dark-adapted leaves is characterized by the multiphase kinetics with a lag-phase, which duration elongates with the dark-adaptation time. Analyzing effects of the uncoupler monensin and artificial electron carrier methylviologen (MV) on photooxidation of P700 and slow induction of chlorophyll a fluorescence (SIF), we could ascribe different phases of transient kinetics of electron transport processes in dark-adapted leaves to the following regulatory mechanisms: (i) acceleration of electron transfer on the acceptor side of PSI, (ii) pH-dependent modulation of the intersystem electron flow, and (iii) re-distribution of electron fluxes between alternative (linear, cyclic, and pseudocyclic) pathways. Monensin significantly decreases a level of P700(+) and inhibits SIF. MV, which mediates electron flow from PSI to O2 with consequent formation of H2O2, promotes a rapid photooxidation of P700 without any lag-phase peculiar to untreated leaves. MV-mediated water-water cycle (H2O→PSII→PSI→MV→O2→H2O2→H2O) is accompanied by generation of ascorbate free radicals. This suggests that the ascorbate peroxidase system of defense against reactive oxygen species is active in chloroplasts of H. rosa-sinensis leaves. In DCMU-treated chloroplasts with inhibited PSII, the contribution of cyclic electron flow is insignificant as compared to linear electron flow. For analysis of induction events, we have simulated electron transport processes within the framework of our generalized mathematical model of oxygenic photosynthesis, which takes into account pH-dependent mechanisms of electron transport control and re-distribution of electron fluxes between alternative pathways. The model adequately describes the main peculiarities of P700(+) induction and dynamics of the intersystem electron transport. Copyright © 2015 Elsevier B.V. All rights reserved.

Osthole induces apoptosis, suppresses cell-cycle progression and proliferation of cancer cells.

PubMed

Jarząb, Agata; Grabarska, Aneta; Kiełbus, Michał; Jeleniewicz, Witold; Dmoszyńska-Graniczka, Magdalena; Skalicka-Woźniak, Krystyna; Sieniawska, Elwira; Polberg, Krzysztof; Stepulak, Andrzej

2014-11-01

The aim of the present study was to determine the effects of osthole on cell proliferation and viability, cell-cycle progression and induction of apoptosis in human laryngeal cancer RK33 and human medulloblastoma TE671 cell lines. Cell viability was measured by means of the MTT method and cell proliferation by the 5-bromo-2-deoxyuridine (BrdU) incorporation assay. Cell-cycle progression was determined by flow cytometry, and induction of apoptosis by release of oligonucleosomes to the cytosol. The gene expression was estimated by a quantitative polymerase chain reaction (qPCR) method. High-performance counter-current chromatography (HPCCC) was applied for isolation of osthole from fruits of Mutellina purpurea. Osthole decreased proliferation and cell viability of cancer cells in a dose-dependent manner. The tested compound induced apoptosis, increased the cell numbers in G1 and decreased cell number in S/G2 phases of the cell cycle, differentially regulating CDKN1A and TP53 gene expression depending on cancer cell type. Osthole could be considered as a potential compound for cancer therapy and chemoprevention. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Matrix Conditions and KLF2-Dependent Induction of Heme Oxygenase-1 Modulate Inhibition of HCV Replication by Fluvastatin

PubMed Central

Singethan, Katrin; Sirma, Hüseyin; Keller, Amelie Dorothea; Rosal, Sergio René Perez; Schrader, Jörg; Loscher, Christine; Volz, Tassilo; Bartenschlager, Ralf; Lohmann, Volker; Protzer, Ulrike; Dandri, Maura; Lohse, Ansgar W.; Tiegs, Gisa; Sass, Gabriele

2014-01-01

Background & Aims HMG-CoA-reductase-inhibitors (statins) have been shown to interfere with HCV replication in vitro. We investigated the mechanism, requirements and contribution of heme oxygenase-1(HO-1)-induction by statins to interference with HCV replication. Methods HO-1-induction by fluva-, simva-, rosuva-, atorva- or pravastatin was correlated to HCV replication, using non-infectious replicon systems as well as the infectious cell culture system. The mechanism of HO-1-induction by statins as well as its relevance for interference with HCV replication was investigated using transient or permanent knockdown cell lines. Polyacrylamide(PAA) gels of different density degrees or the Rho-kinase-inhibitor Hydroxyfasudil were used in order to mimic matrix conditions corresponding to normal versus fibrotic liver tissue. Results All statins used, except pravastatin, decreased HCV replication and induced HO-1 expression, as well as interferon response in vitro. HO-1-induction was mediated by reduction of Bach1 expression and induction of the Nuclear factor (erythroid-derived 2)-like 2 (NRF2) cofactor Krueppel-like factor 2 (KLF2). Knockdown of KLF2 or HO-1 abrogated effects of statins on HCV replication. HO-1-induction and anti-viral effects of statins were more pronounced under cell culture conditions mimicking advanced stages of liver disease. Conclusions Statin-mediated effects on HCV replication seem to require HO-1-induction, which is more pronounced in a microenvironment resembling fibrotic liver tissue. This implicates that certain statins might be especially useful to support HCV therapy of patients at advanced stages of liver disease. PMID:24801208

Time course of the estradiol-dependent induction of oxytocin receptor binding in the ventromedial hypothalamic nucleus of the rat

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

Johnson, A.E.; Ball, G.F.; Coirini, H.

1989-09-01

Oxytocin (OT) transmission is involved in the steroid-dependent display of sexual receptivity in rats. One of the biochemical processes stimulated by the ovarian steroid 17 beta-estradiol (E2) that is relevant to reproduction is the induction of OT receptor binding in the ventromedial hypothalamic nucleus (VMN). The purpose of these experiments was to determine if E2-induced changes in OT receptor binding in the VMN occur within a time frame relevant to cyclic changes in ovarian steroid secretion. OT receptor binding was measured in the VMN of ovariectomized rats implanted for 0-96 h with E2-containing Silastic capsules. The rate of decay ofmore » OT receptor binding was measured in another group of animals 6-48 h after capsule removal. Receptors were labeled with the specific OT receptor antagonist ({sup 125}I)d(CH2)5(Tyr(Me)2,Thr4,Tyr-NH2(9))OVT, and binding was measured with quantitative autoradiographic methods. In addition, plasma E2 levels and uterine weights were assessed in animals from each treatment condition. Significant increases in E2-dependent OT receptor binding and uterine weight occurred within 24 h of steroid treatment. After E2 withdrawal, OT receptor binding and uterine weight decreased significantly within 24 h. These results are consistent with the hypothesis that steroid modulation of OT receptor binding is necessary for the induction of sexual receptivity.« less

Time-dependent upregulation of electron transport with concomitant induction of regulated excitation dissipation in Haslea diatoms.

PubMed

Perkins, R; Williamson, C; Lavaud, J; Mouget, J-L; Campbell, D A

2018-04-16

Photoacclimation by strains of Haslea "blue" diatom species H. ostrearia and H. silbo sp. nov. ined. was investigated with rapid light curves and induction-recovery curves using fast repetition rate fluorescence. Cultures were grown to exponential phase under 50 µmol m -2  s -1 photosynthetic available radiation (PAR) and then exposed to non-sequential rapid light curves where, once electron transport rate (ETR) had reached saturation, light intensity was decreased and then further increased prior to returning to near growth light intensity. The non-sequential rapid light curve revealed that ETR was not proportional to the instantaneously applied light intensity, due to rapid photoacclimation. Changes in the effective absorption cross sections for open PSII reaction centres (σ PSII ') or reaction centre connectivity (ρ) did not account for the observed increases in ETR under extended high light. σ PSII ' in fact decreased as a function of a time-dependent induction of regulated excitation dissipation Y(NPQ), once cells were at or above a PAR coinciding with saturation of ETR. Instead, the observed increases in ETR under extended high light were explained by an increase in the rate of PSII reopening, i.e. Q A - oxidation. This acceleration of electron transport was strictly light dependent and relaxed within seconds after a return to low light or darkness. The time-dependent nature of ETR upregulation and regulated NPQ induction was verified using induction-recovery curves. Our findings show a time-dependent induction of excitation dissipation, in parallel with very rapid photoacclimation of electron transport, which combine to make ETR independent of short-term changes in PAR. This supports a selective advantage for these diatoms when exposed to fluctuating light in their environment.

Inductive specification and axonal orientation of spinal neurons mediated by divergent bone morphogenetic protein signaling pathways

PubMed Central

2011-01-01

Background Bone morphogenetic protein (BMP)7 evokes both inductive and axon orienting responses in dorsal interneurons (dI neurons) in the developing spinal cord. These events occur sequentially during the development of spinal neurons but in these and other cell types such inductive and acute chemotactic responses occur concurrently, highlighting the requirement for divergent intracellular signaling. Both type I and type II BMP receptor subtypes have been implicated selectively in orienting responses but it remains unclear how, in a given cell, divergence occurs. We have examined the mechanisms by which disparate BMP7 activities are generated in dorsal spinal neurons. Results We show that widely different threshold concentrations of BMP7 are required to elicit the divergent inductive and axon orienting responses. Type I BMP receptor kinase activity is required for activation of pSmad signaling and induction of dI character by BMP7, a high threshold response. In contrast, neither type I BMP receptor kinase activity nor Smad1/5/8 phosphorylation is involved in the low threshold orienting responses of dI axons to BMP7. Instead, BMP7-evoked axonal repulsion and growth cone collapse are dependent on phosphoinositide-3-kinase (PI3K) activation, plausibly through type II receptor signaling. BMP7 stimulates PI3K-dependent signaling in dI neurons. BMP6, which evokes neural induction but does not have orienting activity, activates Smad signaling but does not stimulate PI3K. Conclusions Divergent signaling through pSmad-dependent and PI3K-dependent (Smad-independent) mechanisms mediates the inductive and orienting responses of dI neurons to BMP7. A model is proposed whereby selective engagement of BMP receptor subunits underlies choice of signaling pathway. PMID:22085733

Advanced simulation model for IPM motor drive with considering phase voltage and stator inductance

NASA Astrophysics Data System (ADS)

Lee, Dong-Myung; Park, Hyun-Jong; Lee, Ju

2016-10-01

This paper proposes an advanced simulation model of driving system for Interior Permanent Magnet (IPM) BrushLess Direct Current (BLDC) motors driven by 120-degree conduction method (two-phase conduction method, TPCM) that is widely used for sensorless control of BLDC motors. BLDC motors can be classified as SPM (Surface mounted Permanent Magnet) and IPM motors. Simulation model of driving system with SPM motors is simple due to the constant stator inductance regardless of the rotor position. Simulation models of SPM motor driving system have been proposed in many researches. On the other hand, simulation models for IPM driving system by graphic-based simulation tool such as Matlab/Simulink have not been proposed. Simulation study about driving system of IPMs with TPCM is complex because stator inductances of IPM vary with the rotor position, as permanent magnets are embedded in the rotor. To develop sensorless scheme or improve control performance, development of control algorithm through simulation study is essential, and the simulation model that accurately reflects the characteristic of IPM is required. Therefore, this paper presents the advanced simulation model of IPM driving system, which takes into account the unique characteristic of IPM due to the position-dependent inductances. The validity of the proposed simulation model is validated by comparison to experimental and simulation results using IPM with TPCM control scheme.

Comparison of some dispersion-corrected and traditional functionals with CCSD(T) and MP2 ab initio methods: Dispersion, induction, and basis set superposition error

NASA Astrophysics Data System (ADS)

Roy, Dipankar; Marianski, Mateusz; Maitra, Neepa T.; Dannenberg, J. J.

2012-10-01

We compare dispersion and induction interactions for noble gas dimers and for Ne, methane, and 2-butyne with HF and LiF using a variety of functionals (including some specifically parameterized to evaluate dispersion interactions) with ab initio methods including CCSD(T) and MP2. We see that inductive interactions tend to enhance dispersion and may be accompanied by charge-transfer. We show that the functionals do not generally follow the expected trends in interaction energies, basis set superposition errors (BSSE), and interaction distances as a function of basis set size. The functionals parameterized to treat dispersion interactions often overestimate these interactions, sometimes by quite a lot, when compared to higher level calculations. Which functionals work best depends upon the examples chosen. The B3LYP and X3LYP functionals, which do not describe pure dispersion interactions, appear to describe dispersion mixed with induction about as accurately as those parametrized to treat dispersion. We observed significant differences in high-level wavefunction calculations in a basis set larger than those used to generate the structures in many of the databases. We discuss the implications for highly parameterized functionals based on these databases, as well as the use of simple potential energy for fitting the parameters rather than experimentally determinable thermodynamic state functions that involve consideration of vibrational states.

Comparison of some dispersion-corrected and traditional functionals with CCSD(T) and MP2 ab initio methods: dispersion, induction, and basis set superposition error.

PubMed

Roy, Dipankar; Marianski, Mateusz; Maitra, Neepa T; Dannenberg, J J

2012-10-07

We compare dispersion and induction interactions for noble gas dimers and for Ne, methane, and 2-butyne with HF and LiF using a variety of functionals (including some specifically parameterized to evaluate dispersion interactions) with ab initio methods including CCSD(T) and MP2. We see that inductive interactions tend to enhance dispersion and may be accompanied by charge-transfer. We show that the functionals do not generally follow the expected trends in interaction energies, basis set superposition errors (BSSE), and interaction distances as a function of basis set size. The functionals parameterized to treat dispersion interactions often overestimate these interactions, sometimes by quite a lot, when compared to higher level calculations. Which functionals work best depends upon the examples chosen. The B3LYP and X3LYP functionals, which do not describe pure dispersion interactions, appear to describe dispersion mixed with induction about as accurately as those parametrized to treat dispersion. We observed significant differences in high-level wavefunction calculations in a basis set larger than those used to generate the structures in many of the databases. We discuss the implications for highly parameterized functionals based on these databases, as well as the use of simple potential energy for fitting the parameters rather than experimentally determinable thermodynamic state functions that involve consideration of vibrational states.

Comparison of some dispersion-corrected and traditional functionals with CCSD(T) and MP2 ab initio methods: Dispersion, induction, and basis set superposition error

PubMed Central

Roy, Dipankar; Marianski, Mateusz; Maitra, Neepa T.; Dannenberg, J. J.

2012-01-01

We compare dispersion and induction interactions for noble gas dimers and for Ne, methane, and 2-butyne with HF and LiF using a variety of functionals (including some specifically parameterized to evaluate dispersion interactions) with ab initio methods including CCSD(T) and MP2. We see that inductive interactions tend to enhance dispersion and may be accompanied by charge-transfer. We show that the functionals do not generally follow the expected trends in interaction energies, basis set superposition errors (BSSE), and interaction distances as a function of basis set size. The functionals parameterized to treat dispersion interactions often overestimate these interactions, sometimes by quite a lot, when compared to higher level calculations. Which functionals work best depends upon the examples chosen. The B3LYP and X3LYP functionals, which do not describe pure dispersion interactions, appear to describe dispersion mixed with induction about as accurately as those parametrized to treat dispersion. We observed significant differences in high-level wavefunction calculations in a basis set larger than those used to generate the structures in many of the databases. We discuss the implications for highly parameterized functionals based on these databases, as well as the use of simple potential energy for fitting the parameters rather than experimentally determinable thermodynamic state functions that involve consideration of vibrational states. PMID:23039587

The growth transformation of human B cells involves superinduction of hsp70 and hsp90.

PubMed

Cheung, R K; Dosch, H M

1993-04-01

Epstein-Barr virus (EBV) is a latent human herpes virus associated with a range of malignant and non-malignant disorders. EBV binds to CD21 virus receptors on B lymphocytes and growth transforms these cells; in susceptible (e.g., immunodeficient) hosts such cells rapidly expand into fatal lymphomas. Virus binding and infection trigger a cascade of cellular events which are transformation prerequisite and analogous to non-oncogenic cell activation events but which differ in several quantitative or qualitative respects. Unique trans-membrane Ca2+ currents, Na+/H+ exchange, as well as tyrosine phosphorylation and p56lck-gene induction suggest that even early on the transformation process has oncogenic specificity. In this report we describe that two additional cellular gene families, the stress proteins hsp70 and hsp90, are coordinately induced at mRNA and protein levels and, quite different from hsp induction by thermal stress, this induction is dependent on EBV-induced trans-membrane Ca2+ currents. Blockade of hsp induction prevents transformation. The kinetics and induction prerequisites set this response well apart from reported responses to thermal or viral stress protein induction. Like p56lck-, hsp induction is purely a post-receptor binding event and not dependent on expression of any viral gene. The induction kinetics, with a peak at approximately 12-16 hr and subsequent decline to control levels, considerably extend the chronological map of elements in the CD21-dependent branch of the transformation pathway and suggest a specific role of induced hsp different from the cell cycle-related functions observed in other cell systems.

Methods for assessing pre-induction cervical ripening

PubMed Central

Ezebialu, Ifeanyichukwu U; Eke, Ahizechukwu C; Eleje, George U; Nwachukwu, Chukwuemeka E

2015-01-01

Background Induction of labour is the artificial initiation of labour in a pregnant woman after the age of fetal viability but without any objective evidence of active phase labour and with intact fetal membranes. The need for induction of labour may arise due to a problem in the mother, her fetus or both, and the procedure may be carried out at or before term. Obstetricians have long known that for this to be successful, it is important that the uterine cervix (the neck of the womb) has favourable characteristics in terms of readiness to go into the labour state. Objectives To compare Bishop score with any other method for assessing pre-induction cervical ripening in women admitted for induction of labour. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 March 2015) and reference lists of retrieved studies to identify randomised controlled trials (RCTs). Selection criteria All RCTs comparing Bishop score with any other methods of pre-induction cervical assessment in women admitted for induction of labour. Cluster-RCTs were eligible for inclusion but none were identified. Quasi-RCTs and studies using a cross-over design were not eligible for inclusion. Studies published in abstract form were eligible for inclusion if they provided sufficient information. Comparisons could include the following. Bishop score versus transvaginal ultrasound (TVUS). Bishop score versus Insulin-like growth factor binding protein-1 (IGFBP-1). Bishop score versus vaginal fetal fibronectin (fFN). However, we only identified data for a comparison of Bishop score versus TVUS. Data collection and analysis Two review authors independently assessed the trials for inclusion, extracted the data and assessed trial quality. Data were checked for accuracy. Main results We included two trials that recruited a total of 234 women. The overall risk of bias was low for the two studies. Both studies compared Bishop score withTVUS. The two included studies did not show any clear difference between the Bishop score and TVUS groups for the following main outcomes: vaginal birth (RR 1.07, 95% CI 0.92 to 1.25, moderate quality evidence), caesarean delivery (RR 0.81, 95% CI 0.49 to 1.34, moderate quality evidence), neonatal admission into neonatal intensive care unit (RR 1.67, 95% CI 0.41 to 6.71, moderate quality evidence). Both studies only provided median data in relation to induction-delivery interval and reported no clear difference between the Bishop and TVUS groups. Perinatal mortality was not reported in the included studies. For the review's secondary outcomes, the need for misoprostol for cervical ripening was more frequent in the TVUS group compared to the Bishop score group (RR 0.52, 95% CI 0.41 to 0.66, two studies, 234 women, moderate quality evidence). In contrast, there were no clear differences between the Bishop scope and TVUS groups in terms of meconium staining of the amniotic fluid, fetal heart rate abnormality in labour, and Apgar score less than seven. Only one trial reported median data on the induction-delivery interval and induction to active phase interval, the trialist reported no difference between the Bishop group and the TVUS group for this outcome. Neither of the included studies reported on uterine rupture. Authors' conclusions Moderate quality evidence from two small RCTs involving 234 women that compared two different methods for assessing pre-induction cervical ripening (Bishop score and TVUS) did not demonstrate superiority of one method over the other in terms of the main outcomes assessed in this review. We did not identify any data relating to perinatal mortality. Whilst use of TVUS was associated with an increased need for misoprostol for cervical ripening, both methods could be complementary. The choice of a particular method of assessing pre-induction cervical ripening may differ depending on the environment and need where one is practicing since some methods (i.e. TVUS) may not be readily available and affordable in resource-poor settings where the sequelae of labour and its management is prevalent. The evidence in this review is based on two studies that enrolled a small number of women and there is insufficient evidence to support the use of TVUS over the standard digital vaginal assessment in pre-induction cervical ripening. Further adequately powered RCTs involving TVUS and the Bishop score and including other methods of pre-induction cervical ripening assessment are warranted. Such studies need to address uterine rupture, perinatal mortality, optimal cut-off value of the cervical length and Bishop score to classify women as having favourable or unfavourable cervices and cost should be included as an outcome. PLAIN LANGUAGE SUMMARY Methods for assessing pre-induction cervical ripening, the ability of the cervix to open in response to spontaneous uterine contractions In this review, researchers from The Cochrane Collaboration examined a comparison between the Bishop score and any other method for checking pre-induction cervical ripening in women admitted for induction of labour. The Bishop score is the traditional method of determining the readiness of the cervix to open (dilate) before labour induction. It also assesses the position, softening and shortening of the cervix, and the location of the presenting part of the baby. After searching for relevant trials up to 31 March 2015, we included two randomised controlled trials that recruited 234 pregnant women. What are the methods for pre-induction softening of the neck of womb and why is it important to soften the neck of womb before induction of labour? Induction of labour is the non-natural process of starting labour in a pregnant woman after the age the baby is more likely to survive following delivery, when there is no clear evidence of serious onset of labour and the membranes covering the baby are unruptured. Induction of labour may be needed because of a problem in the mother, or her baby or both, and is carried out at or before the ninth (last) month of pregnancy. Obstetricians (specialist caring for pregnant women) have long known that for this to be successful, it is important that the uterine cervix (the neck of the womb) has the favourable characteristics that make it ready to go into the labour. The delivery method and total duration of labour are affected by many factors and cervical readiness (ripeness) is just one of these. What the research says Moderate quality evidence was available from the two included studies which compared the Bishop score with transvaginal ultrasound (TVUS) (ultrasound done through the vagina). The studies were considered to be at a low risk of bias. The need for misoprostol (a drug) for softening the cervix (cervical ripening) was more common in the TVUS arm. No clear difference was seen between the two methods in terms of vaginal birth, caesarean delivery, admission of the newborn into the neonatal intensive care unit, meconium staining of the amniotic fluid, abnormal heart beat of the baby within the womb whilst the mother was in labour and Apgar score less than seven (difficulty of the baby establishing life and other life movements on its own immediately after childbirth). None of the included studies reported on tears of the womb or death of the baby just before, during or immediately after childbirth. We did not find any studies that compared Bishop score with any other methods such as the presence of vaginal fetal fibronectin or insulin-like growth factor binding protein-1. Authors conclusions Although the overall quality of evidence is moderate, there is no difference in outcomes between the two methods (Bishop score and TVUS) apart from the increased need of misoprostol in the TVUS group. Both methods could be useful to each other, or complementary as the Bishop score does not need any special equipment and uses digital examination which is required to induce labour (to insert a cervical ripening agent, rupture the membranes or separate them from the cervix) but TVUS can give additional information that may affect the course and management of the labour. The choice of a particular method may differ depending on the environment and need since TVUS requires training and may not be readily available and affordable in resource-poor countries. Future research The two included studies involved a small number of women and further studies are needed. Such studies should include outcomes such as rupture of the womb, perinatal mortality, most appropriate cut-off value for the cervical length and Bishop score to classify women as having ripe or unripe cervices, and cost. PMID:26068943

Particle-in-cell simulations of electron beam control using an inductive current divider

DOE PAGES

Swanekamp, S. B.; Angus, J. R.; Cooperstein, G.; ...

2015-11-18

Kinetic, time-dependent, electromagnetic, particle-in-cell simulations of the inductive current divider are presented. The inductive current divider is a passive method for controlling the trajectory of an intense, hollow electron beam using a vacuum structure that inductively splits the beam’s return current. The current divider concept was proposed and studied theoretically in a previous publication [Phys. Plasmas 22, 023107 (2015)] A central post carries a portion of the return current (I 1) while the outer conductor carries the remainder (I 2) with the injected beam current given by I b=I 1+I 2. The simulations are in agreement with the theory whichmore » predicts that the total force on the beam trajectory is proportional to (I 2-I 1) and the force on the beam envelope is proportional to I b. For a fixed central post, the beam trajectory is controlled by varying the outer conductor radius which changes the inductance in the return-current path. The simulations show that the beam emittance is approximately constant as the beam propagates through the current divider to the target. As a result, independent control over both the current density and the beam angle at the target is possible by choosing the appropriate return-current geometry.« less

Controlling hollow relativistic electron beam orbits with an inductive current divider

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

Swanekamp, S. B.; Richardson, A. S.; Angus, J. R.

2015-02-15

A passive method for controlling the trajectory of an intense, hollow electron beam is proposed using a vacuum structure that inductively splits the beam's return current. A central post carries a portion of the return current (I{sub 1}), while the outer conductor carries the remainder (I{sub 2}). An envelope equation appropriate for a hollow electron beam is derived and applied to the current divider. The force on the beam trajectory is shown to be proportional to (I{sub 2}-I{sub 1}), while the average force on the envelope (the beam width) is proportional to the beam current I{sub b} = (I{sub 2} + I{sub 1}). Themore » values of I{sub 1} and I{sub 2} depend on the inductances in the return-current path geometries. Proper choice of the return-current geometries determines these inductances and offers control over the beam trajectory. Solutions using realistic beam parameters show that, for appropriate choices of the return-current-path geometry, the inductive current divider can produce a beam that is both pinched and straightened so that it approaches a target at near-normal incidence with a beam diameter that is on the order of a few mm.« less

The Heuristic Value of p in Inductive Statistical Inference

PubMed Central

Krueger, Joachim I.; Heck, Patrick R.

2017-01-01

Many statistical methods yield the probability of the observed data – or data more extreme – under the assumption that a particular hypothesis is true. This probability is commonly known as ‘the’ p-value. (Null Hypothesis) Significance Testing ([NH]ST) is the most prominent of these methods. The p-value has been subjected to much speculation, analysis, and criticism. We explore how well the p-value predicts what researchers presumably seek: the probability of the hypothesis being true given the evidence, and the probability of reproducing significant results. We also explore the effect of sample size on inferential accuracy, bias, and error. In a series of simulation experiments, we find that the p-value performs quite well as a heuristic cue in inductive inference, although there are identifiable limits to its usefulness. We conclude that despite its general usefulness, the p-value cannot bear the full burden of inductive inference; it is but one of several heuristic cues available to the data analyst. Depending on the inferential challenge at hand, investigators may supplement their reports with effect size estimates, Bayes factors, or other suitable statistics, to communicate what they think the data say. PMID:28649206

Impact of equalizing currents on losses and torque ripples in electrical machines with fractional slot concentrated windings

NASA Astrophysics Data System (ADS)

Toporkov, D. M.; Vialcev, G. B.

2017-10-01

The implementation of parallel branches is a commonly used manufacturing method of the realizing of fractional slot concentrated windings in electrical machines. If the rotor eccentricity is enabled in a machine with parallel branches, the equalizing currents can arise. The simulation approach of the equalizing currents in parallel branches of an electrical machine winding based on magnetic field calculation by using Finite Elements Method is discussed in the paper. The high accuracy of the model is provided by the dynamic improvement of the inductances in the differential equation system describing a machine. The pre-computed table flux linkage functions are used for that. The functions are the dependences of the flux linkage of parallel branches on the branches currents and rotor position angle. The functions permit to calculate self-inductances and mutual inductances by partial derivative. The calculated results obtained for the electric machine specimen are presented. The results received show that the adverse combination of design solutions and the rotor eccentricity leads to a high value of the equalizing currents and windings heating. Additional torque ripples also arise. The additional ripples harmonic content is not similar to the cogging torque or ripples caused by the rotor eccentricity.

The Heuristic Value of p in Inductive Statistical Inference.

PubMed

Krueger, Joachim I; Heck, Patrick R

2017-01-01

Many statistical methods yield the probability of the observed data - or data more extreme - under the assumption that a particular hypothesis is true. This probability is commonly known as 'the' p -value. (Null Hypothesis) Significance Testing ([NH]ST) is the most prominent of these methods. The p -value has been subjected to much speculation, analysis, and criticism. We explore how well the p -value predicts what researchers presumably seek: the probability of the hypothesis being true given the evidence, and the probability of reproducing significant results. We also explore the effect of sample size on inferential accuracy, bias, and error. In a series of simulation experiments, we find that the p -value performs quite well as a heuristic cue in inductive inference, although there are identifiable limits to its usefulness. We conclude that despite its general usefulness, the p -value cannot bear the full burden of inductive inference; it is but one of several heuristic cues available to the data analyst. Depending on the inferential challenge at hand, investigators may supplement their reports with effect size estimates, Bayes factors, or other suitable statistics, to communicate what they think the data say.

Primula auriculata Extracts Exert Cytotoxic and Apoptotic Effects against HT-29 Human Colon Adenocarcinoma Cells.

PubMed

Behzad, Sahar; Ebrahim, Karim; Mosaddegh, Mahmoud; Haeri, Ali

2016-01-01

Primula auriculata (Tootia) is one of the most important local medicinal plants in Hamedan district, Iran. To investigate cytotoxicity and apoptosis induction of crude methanolic extract and different fraction of it, we compared several methods on HT-29 human colon Adenocarcinoma cells. Cancer cell proliferation was measured by 3-(4, 5‑dimethylthiazolyl)2, 5‑diphenyl‑tetrazolium bromide (MTT) assay and apoptosis induction was analyzed by fluorescence microscopy (acridin orange/ethidium bromide, annexin V/propidium iodide staining, TUNEL assay and Caspase-3 activity assay). Crude methanolic extract (CM) inhibited the growth of malignant cells in a dose-dependent manner. Among solvent fractions, the dichloromethane fraction (CF) was found to be the most toxic compared to other fractions. With double staining methods, high percentage of 40 µg/mL of (CM) and (CF) treated cells exhibited typical characteristics of apoptotic cells. Apoptosis induction was also revealed by apoptotic fragmentation of nuclear DNA and activation of caspas-3 in treated cells. These findings indicate that crude methanolic extract and dichloromethan fraction of P.auriculata induced apoptosis and inhibited proliferation in colon cancer cells and could be used as a source for new lead structures in drug design to combat colon cancer.

Impact of Cannabis Use During Stabilization on Methadone Maintenance Treatment

PubMed Central

Scavone, Jillian L.; Sterling, Robert C.; Weinstein, Stephen P.; Van Bockstaele, Elisabeth J.

2016-01-01

Background and Objectives Illicit drug use, particularly of cannabis, is common among opiate-dependent individuals, and has the potential to impact treatment in a negative manner. Methods To examine this, patterns of cannabis use prior to and during methadone maintenance treatment (MMT) were examined to assess possible cannabis-related effects on MMT, particularly during methadone stabilization. Retrospective chart analysis was used to examine outpatient records of patients undergoing MMT (n=91), focusing specifically on past and present cannabis use and its association with opiate abstinence, methadone dose stabilization, and treatment compliance. Results Objective rates of cannabis use were high during methadone induction, dropping significantly following dose stabilization. History of cannabis use correlated with cannabis use during MMT, but did not negatively impact the methadone induction process. Pilot data also suggested that objective ratings of opiate withdrawal decrease in MMT patients using cannabis during stabilization. Conclusions and Scientific Significance The present findings may point to novel interventions to be employed during treatment for opiate dependence that specifically target cannabinoid-opioid system interactions. PMID:23795873

Ethanol Induction of CYP2A5: Role of CYP2E1-ROS-Nrf2 Pathway

PubMed Central

Lu, Yongke; Zhang, Xu Hannah

2012-01-01

Chronic ethanol consumption was previously shown to induce CYP2A5 in mice, and this induction of CYP2A5 by ethanol was CYP2E1 dependent. In this study, the mechanisms of CYP2E1-dependent ethanol induction of CYP2A5 were investigated. CYP2E1 was induced by chronic ethanol consumption to the same degree in wild-type (WT) mice and CYP2A5 knockout (Cyp2a5 –/–) mice, suggesting that unlike the CYP2E1-dependent ethanol induction of CYP2A5, ethanol induction of CYP2E1 is not CYP2A5 dependent. Microsomal ethanol oxidation was about 25% lower in Cyp2a5 –/– mice compared with that in WT mice, suggesting that CYP2A5 can oxidize ethanol although to a lesser extent than CYP2E1 does. CYP2A5 was induced by short-term ethanol consumption in human CYP2E1 transgenic knockin (Cyp2e1 –/– KI) mice but not in CYP2E1 knockout (Cyp2e1 –/–) mice. The redox-sensitive transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2) was also induced by acute ethanol in Cyp2e1 –/– KI mice but not in Cyp2e1 –/– mice. Ethanol induction of CYP2A5 in Nrf2 knockout (Nrf2 –/–) mice was lower compared with that in WT mice, whereas CYP2E1 induction by ethanol was comparable in WT and Nrf2 –/– mice. Antioxidants (N-acetyl-cysteine and vitamin C), which blocked oxidative stress induced by chronic ethanol in WT mice and acute ethanol in Cyp2e1 –/– KI mice, also blunted the induction of CYP2A5 and Nrf2 by ethanol but not the induction of CYP2E1 by ethanol. These results suggest that oxidative stress induced by ethanol via induction of CYP2E1 upregulates Nrf2 activity, which in turn regulates ethanol induction of CYP2A5. Results obtained from primary hepatocytes, mice gavaged with binge ethanol or fed chronic ethanol, show that Nrf2-regulated ethanol induction of CYP2A5 protects against ethanol-induced steatosis. PMID:22552773

Induction of a Torpor-Like State by 5’-AMP Does Not Depend on H2S Production

PubMed Central

Dugbartey, George J.; Bouma, Hjalmar R.; Strijkstra, Arjen M.; Boerema, Ate S.; Henning, Robert H.

2015-01-01

Background Therapeutic hypothermia is used to reduce ischemia/reperfusion injury (IRI) during organ transplantation and major surgery, but does not fully prevent organ injury. Interestingly, hibernating animals undergo repetitive periods of low body temperature called ‘torpor’ without signs of organ injury. Recently, we identified an essential role of hydrogen sulfide (H2S) in entrance into torpor and preservation of kidney integrity during hibernation. A torpor-like state can be induced pharmacologically by injecting 5’-Adenosine monophosphate (5’-AMP). The mechanism by which 5’-AMP leads to the induction of a torpor-like state, and the role of H2S herein, remains to be unraveled. Therefore, we investigated whether induction of a torpor-like state by 5-AMP depends on H2S production. Methods To study the role of H2S on the induction of torpor, amino-oxyacetic acid (AOAA), a non-specific inhibitor of H2S, was administered before injection with 5'-AMP to block endogenous H2S production in Syrian hamster. To assess the role of H2S on maintenance of torpor induced by 5’-AMP, additional animals were injected with AOAA during torpor. Key Results During the torpor-like state induced by 5’-AMP, the expression of H2S- synthesizing enzymes in the kidneys and plasma levels of H2S were increased. Blockade of these enzymes inhibited the rise in the plasma level of H2S, but neither precluded torpor nor induced arousal. Remarkably, blockade of endogenous H2S production was associated with increased renal injury. Conclusions Induction of a torpor-like state by 5’-AMP does not depend on H2S, although production of H2S seems to attenuate renal injury. Unraveling the mechanisms by which 5’-AMP reduces the metabolism without organ injury may allow optimization of current strategies to limit (hypothermic) IRI and improve outcome following organ transplantation, major cardiac and brain surgery. PMID:26295351

Multilayered Regulation of Ethylene Induction Plays a Positive Role in Arabidopsis Resistance against Pseudomonas syringae1[OPEN

PubMed Central

Guan, Rongxia; Su, Jianbin; Meng, Xiangzong; Li, Sen; Liu, Yidong; Xu, Juan; Zhang, Shuqun

2015-01-01

Ethylene, a key phytohormone involved in plant-pathogen interaction, plays a positive role in plant resistance against fungal pathogens. However, its function in plant bacterial resistance remains unclear. Here, we report a detailed analysis of ethylene induction in Arabidopsis (Arabidopsis thaliana) in response to Pseudomonas syringae pv tomato DC3000 (Pst). Ethylene biosynthesis is highly induced in both pathogen/microbe-associated molecular pattern (PAMP)-triggered immunity and effector-triggered immunity (ETI), and the induction is potentiated by salicylic acid (SA) pretreatment. In addition, Pst actively suppresses PAMP-triggered ethylene induction in a type III secretion system-dependent manner. SA potentiation of ethylene induction is dependent mostly on MITOGEN-ACTIVATED PROTEIN KINASE6 (MPK6) and MPK3 and their downstream ACS2 and ACS6, two type I isoforms of 1-aminocyclopropane-1-carboxylic acid synthases (ACSs). ACS7, a type III ACS whose expression is enhanced by SA pretreatment, is also involved. Pst expressing the avrRpt2 effector gene (Pst-avrRpt2), which is capable of triggering ETI, induces a higher level of ethylene production, and the elevated portion is dependent on SALICYLIC ACID INDUCTION DEFICIENT2 and NONEXPRESSER OF PATHOGENESIS-RELATED GENE1, two key players in SA biosynthesis and signaling. High-order ACS mutants with reduced ethylene induction are more susceptible to both Pst and Pst-avrRpt2, demonstrating a positive role of ethylene in plant bacterial resistance mediated by both PAMP-triggered immunity and ETI. PMID:26265775

The use of nutritional supplements to induce ketosis and reduce symptoms associated with keto-induction: a narrative review.

PubMed

Harvey, Cliff J D C; Schofield, Grant M; Williden, Micalla

2018-01-01

Adaptation to a ketogenic diet (keto-induction) can cause unpleasant symptoms, and this can reduce tolerability of the diet. Several methods have been suggested as useful for encouraging entry into nutritional ketosis (NK) and reducing symptoms of keto-induction. This paper reviews the scientific literature on the effects of these methods on time-to-NK and on symptoms during the keto-induction phase. PubMed, Science Direct, CINAHL, MEDLINE, Alt Health Watch, Food Science Source and EBSCO Psychology and Behavioural Sciences Collection electronic databases were searched online. Various purported ketogenic supplements were searched along with the terms "ketogenic diet", "ketogenic", "ketosis" and ketonaemia (/ ketonemia). Additionally, author names and reference lists were used for further search of the selected papers for related references. Evidence, from one mouse study, suggests that leucine doesn't significantly increase beta-hydroxybutyrate (BOHB) but the addition of leucine to a ketogenic diet in humans, while increasing the protein-to-fat ratio of the diet, doesn't reduce ketosis. Animal studies indicate that the short chain fatty acids acetic acid and butyric acid, increase ketone body concentrations. However, only one study has been performed in humans. This demonstrated that butyric acid is more ketogenic than either leucine or an 8-chain monoglyceride. Medium-chain triglycerides (MCTs) increase BOHB in a linear, dose-dependent manner, and promote both ketonaemia and ketogenesis. Exogenous ketones promote ketonaemia but may inhibit ketogenesis. There is a clear ketogenic effect of supplemental MCTs; however, it is unclear whether they independently improve time to NK and reduce symptoms of keto-induction. There is limited research on the potential for other supplements to improve time to NK and reduce symptoms of keto-induction. Few studies have specifically evaluated symptoms and adverse effects of a ketogenic diet during the induction phase. Those that have typically were not designed to evaluate these variables as primary outcomes, and thus, more research is required to elucidate the role that supplementation might play in encouraging ketogenesis, improve time to NK, and reduce symptoms associated with keto-induction.

Chk2 mediates RITA-induced apoptosis.

PubMed

de Lange, J; Verlaan-de Vries, M; Teunisse, A F A S; Jochemsen, A G

2012-06-01

Reactivation of the p53 tumor-suppressor protein by small molecules like Nutlin-3 and RITA (reactivation of p53 and induction of tumor cell apoptosis) is a promising strategy for cancer therapy. The molecular mechanisms involved in the responses to RITA remain enigmatic. Several groups reported the induction of a p53-dependent DNA damage response. Furthermore, the existence of a p53-dependent S-phase checkpoint has been suggested, involving the checkpoint kinase Chk1. We have recently shown synergistic induction of apoptosis by RITA in combination with Nutlin-3, and we observed concomitant Chk2 phosphorylation. Therefore, we investigated whether Chk2 contributes to the cellular responses to RITA. Strikingly, the induction of apoptosis seemed entirely Chk2 dependent. Transcriptional activity of p53 in response to RITA required the presence of Chk2. A partial rescue of apoptosis observed in Noxa knockdown cells emphasized the relevance of p53 transcriptional activity for RITA-induced apoptosis. In addition, we observed an early p53- and Chk2-dependent block of DNA replication upon RITA treatment. Replicating cells seemed more prone to entering RITA-induced apoptosis. Furthermore, the RITA-induced DNA damage response, which was not a secondary effect of apoptosis induction, was strongly attenuated in cells lacking p53 or Chk2. In conclusion, we identified Chk2 as an essential mediator of the cellular responses to RITA.

Chk2 mediates RITA-induced apoptosis

PubMed Central

de Lange, J; Verlaan-de Vries, M; Teunisse, A F A S; Jochemsen, A G

2012-01-01

Reactivation of the p53 tumor-suppressor protein by small molecules like Nutlin-3 and RITA (reactivation of p53 and induction of tumor cell apoptosis) is a promising strategy for cancer therapy. The molecular mechanisms involved in the responses to RITA remain enigmatic. Several groups reported the induction of a p53-dependent DNA damage response. Furthermore, the existence of a p53-dependent S-phase checkpoint has been suggested, involving the checkpoint kinase Chk1. We have recently shown synergistic induction of apoptosis by RITA in combination with Nutlin-3, and we observed concomitant Chk2 phosphorylation. Therefore, we investigated whether Chk2 contributes to the cellular responses to RITA. Strikingly, the induction of apoptosis seemed entirely Chk2 dependent. Transcriptional activity of p53 in response to RITA required the presence of Chk2. A partial rescue of apoptosis observed in Noxa knockdown cells emphasized the relevance of p53 transcriptional activity for RITA-induced apoptosis. In addition, we observed an early p53- and Chk2-dependent block of DNA replication upon RITA treatment. Replicating cells seemed more prone to entering RITA-induced apoptosis. Furthermore, the RITA-induced DNA damage response, which was not a secondary effect of apoptosis induction, was strongly attenuated in cells lacking p53 or Chk2. In conclusion, we identified Chk2 as an essential mediator of the cellular responses to RITA. PMID:22158418

Cytotoxicity and Induction of Inflammation by Pepsin in Acid in Bronchial Epithelial Cells

PubMed Central

Bathoorn, Erik; Daly, Paul; Gaiser, Birgit; Sternad, Karl; Poland, Craig; MacNee, William; Drost, Ellen M.

2011-01-01

Introduction. Gastroesophageal reflux has been associated with chronic inflammatory diseases and may be a cause of airway remodelling. Aspiration of gastric fluids may cause damage to airway epithelial cells, not only because acidity is toxic to bronchial epithelial cells, but also since it contains digestive enzymes, such as pepsin. Aim. To study whether pepsin enhances cytotoxicity and inflammation in airway epithelial cells, and whether this is pH-dependent. Methods. Human bronchial epithelial cells were exposed to increasing pepsin concentrations in varying acidic milieus, and cell proliferation and cytokine release were assessed. Results. Cell survival was decreased by pepsin exposure depending on its concentration (F = 17.4) and pH level of the medium (F = 6.5) (both P < 0.01). Pepsin-induced interleukin-8 release was greater at lower pH (F = 5.1; P < 0.01). Interleukin-6 induction by pepsin was greater at pH 1.5 compared to pH 2.5 (mean difference 434%; P = 0.03). Conclusion. Pepsin is cytotoxic to bronchial epithelial cells and induces inflammation in addition to acid alone, dependent on the level of acidity. Future studies should assess whether chronic aspiration causes airway remodelling in chronic inflammatory lung diseases. PMID:21785693

tif-dependent induction of colicin E1, prophage lambda, and filamentation in Escherichia coli K-12.

PubMed

Tessman, E S; Peterson, P K

1980-09-01

To help understand how the tif-1 mutation of the recA gene of Escherichia coli confers adenine activability on the recA protein, we used the fact that cytidine plus guanosine inhibits induction of prophage lambda and cell filamentation in a tif-1 mutant, and that adenine reverses this inhibition. We varied the amount of adenine in agar plates containing a fixed amount of cytidine and scored for survivors of three different tif-dependent lethal induction processes. Much more adenine was required for cell killing when cytidine was present than when it was absent. Therefore adenine does not override cytidine inhibition, but instead appears to compete with it for a site of action which may be on the recA protein. The competition is not at the cell transport level. Our results lead to a model in which the tif form of the recA protein is an allosteric enzyme that binds both negative and positive modulators. By varying the adenine-cytidine ratio of the medium it is possible to control the degree of induction in a tif-1 cell. For the three different tif-dependent inductions studied here, least adenine was required for lambda induction and most for lethal filamentation, presumably reflecting requirements for different amounts of activated recA protein in each process. Varying the adenine-cytidine ratio revealed two stable intermediate stages in lambda induction, as well as a stage of colicin E1 induction in which the cells produced colicin without cell death. The rate of filament formation could be similarly controlled. Experiments with tif (ColE1, lambda) gave evidence of a competition between colicin repressor and lambda repressor for activated recA protein.

Induction immunosuppressive therapies in renal transplantation.

PubMed

Gabardi, Steven; Martin, Spencer T; Roberts, Keri L; Grafals, Monica

2011-02-01

Induction immunosuppressive therapies for patients undergoing renal transplantation are reviewed. The goal of induction therapy is to prevent acute rejection during the early posttransplantation period by providing a high degree of immunosuppression at the time of transplantation. Induction therapy is often considered essential to optimize outcomes, particularly in patients at high risk for poor short-term outcomes. All of the induction immunosuppressive agents currently used are biological agents and are either monoclonal (muromonab-CD3, daclizumab, basiliximab, alemtuzumab) or polyclonal (antithymocyte globulin [equine] or antithymocyte globulin [rabbit]) antibodies. Although antithymocyte globulin (rabbit) is not labeled for induction therapy, it is used for this purpose more than any other agent. Basiliximab is not considered as potent an immunosuppressive agent but has a much more favorable adverse-effect profile compared with antithymocyte globulin (rabbit) and is most commonly used in patients at low risk for acute rejection. Rituximab is being studied for use as induction therapy but to date has not demonstrated any significant benefits over placebo. While head-to-head data are available comparing most induction agents, the final decision on the most appropriate induction therapy for a transplant recipient is highly dependent on preexisting medical conditions, donor characteristics, and the maintenance immunosuppressive regimen to be used. No standard induction immunosuppressive regimen exists for patients undergoing renal transplantation. Antithymocyte globulin (rabbit) is the most commonly used agent, whereas basiliximab appears safer. The choice of regimen depends on the preferences of clinicians and institutions.

Reproducible and controllable light induction of in vitro fruiting of the white-rot basidiomycete Pleurotus ostreatus.

PubMed

Arjona, Davinia; Aragón, Carlos; Aguilera, José Antonio; Ramírez, Lucía; Pisabarro, Antonio G

2009-05-01

Fruiting is a crucial developmental process in basidiomycetes yet the genetic and molecular factors that control it are not yet fully understood. The search for fruiting inducers is of major relevance for both basic research and for their use in industrial applications. In this paper, an efficient and reproducible protocol for controlled fruiting induction of Pleurotus ostreatus growing on synthetic medium is described. The protocol is based on the control of light intensity and photoperiod and permits the life cycle for this fungus to be completed in less than two weeks. The fruiting bodies produced by this method release fertile spores after 4-5 d of culture. Our results indicate that fruiting induction is solely dependent on the illumination regime and that it occurs long before the available nutrients are depleted in the culture. This protocol will greatly facilitate molecular and developmental biology research in this fungus as it avoids the need for complex culture media based on lignocellulosic materials or the use of chemical inducers.

Direct comparison of two different mesalamine formulations for the induction of remission in patients with ulcerative colitis: A double-blind, randomized study

PubMed Central

Ito, Hiroaki; Iida, Mitsuo; Matsumoto, Takayuki; Suzuki, Yasuo; Sasaki, Hidetaka; Yoshida, Toyomitsu; Takano, Yuichi; Hibi, Toshifumi

2010-01-01

Background: Mesalamine is the first-line drug for the treatment of ulcerative colitis (UC). We directly compared the efficacy and safety of two mesalamine formulations for the induction of remission in patients with UC. Methods: In a multicenter, double-blind, randomized study, 229 patients with mild-to-moderate active UC were assigned to 4 groups: 66 and 65 received a pH-dependent release formulation of 2.4 g/day (pH-2.4 g) or 3.6 g/day (pH-3.6 g), respectively; 65 received a time-dependent release formulation of 2.25 g/day (Time-2.25 g), and 33 received placebo (Placebo). The drugs were administered three times daily for eight weeks. The primary endpoint was a decrease in the UC disease activity index (UC-DAI). Results: In the full analysis set (n = 225) the decrease in UC-DAI in each group was 1.5 in pH-2.4 g, 2.9 in pH-3.6 g, 1.3 in Time-2.25 g and 0.3 in Placebo, respectively. These results demonstrate the superiority of pH-3.6 g over Time-2.25 g (P = 0.003) and the noninferiority of pH-2.4 g to Time-2.25 g. Among the patients with proctitis-type UC, a significant decrease in UC-DAI was observed in pH-2.4 g and pH-3.6 g as compared to Placebo, but not in Time-2.25 g. No differences were observed in the safety profiles. Conclusions: Higher dose of the pH-dependent release formulation was more effective for induction of remission in patients with mild-to-moderate active UC. Additionally, the pH-dependent release formulation was preferable to the time-dependent release formulation for patients with proctitis-type UC (UMIN Clinical Trials Registry, no. C000000288). (Inflamm Bowel Dis 2010) PMID:20049950

The effect of farrowing induction on colostrum and piglet serum immunocrits is dependent on parity

USDA-ARS?s Scientific Manuscript database

Farrowing induction is a common practice among swine producers to manage timing of farrowing and the labor associated with farrowing. In this experiment, the effect of induction of labor using cloprostenol on day 114 of gestation (n = 88) was compared to our standard farrowing protocol at USMARC (na...

Investigation of optimal method for inducing harmonic motion in tissue using a linear ultrasound phased array--a simulation study.

PubMed

Heikkilä, Janne; Hynynen, Kullervo

2006-04-01

Many noninvasive ultrasound techniques have been developed to explore mechanical properties of soft tissues. One of these methods, Localized Harmonic Motion Imaging (LHMI), has been proposed to be used for ultrasound surgery monitoring. In LHMI, dynamic ultrasound radiation-force stimulation induces displacements in a target that can be measured using pulse-echo imaging and used to estimate the elastic properties of the target. In this initial, simulation study, the use of a one-dimensional phased array is explored for the induction of the tissue motion. The study compares three different dual-frequency and amplitude-modulated single-frequency methods for the inducing tissue motion. Simulations were computed in a homogeneous soft-tissue volume. The Rayleigh integral was used in the simulations of the ultrasound fields and the tissue displacements were computed using a finite-element method (FEM). The simulations showed that amplitude-modulated sonication using a single frequency produced the largest vibration amplitude of the target tissue. These simulations demonstrate that the properties of the tissue motion are highly dependent on the sonication method and that it is important to consider the full three-dimensional distribution of the ultrasound field for controlling the induction of tissue motion.

Detection of stator winding faults in induction motors using three-phase current monitoring.

PubMed

Sharifi, Rasool; Ebrahimi, Mohammad

2011-01-01

The objective of this paper is to propose a new method for the detection of inter-turn short circuits in the stator windings of induction motors. In the previous reported methods, the supply voltage unbalance was the major difficulty, and this was solved mostly based on the sequence component impedance or current which are difficult to implement. Some other methods essentially are included in the offline methods. The proposed method is based on the motor current signature analysis and utilizes three phase current spectra to overcome the mentioned problem. Simulation results indicate that under healthy conditions, the rotor slot harmonics have the same magnitude in three phase currents, while under even 1 turn (0.3%) short circuit condition they differ from each other. Although the magnitude of these harmonics depends on the level of unbalanced voltage, they have the same magnitude in three phases in these conditions. Experiments performed under various load, fault, and supply voltage conditions validate the simulation results and demonstrate the effectiveness of the proposed technique. It is shown that the detection of resistive slight short circuits, without sensitivity to supply voltage unbalance is possible. Copyright © 2010 ISA. Published by Elsevier Ltd. All rights reserved.

Multilayered Regulation of Ethylene Induction Plays a Positive Role in Arabidopsis Resistance against Pseudomonas syringae.

PubMed

Guan, Rongxia; Su, Jianbin; Meng, Xiangzong; Li, Sen; Liu, Yidong; Xu, Juan; Zhang, Shuqun

2015-09-01

Ethylene, a key phytohormone involved in plant-pathogen interaction, plays a positive role in plant resistance against fungal pathogens. However, its function in plant bacterial resistance remains unclear. Here, we report a detailed analysis of ethylene induction in Arabidopsis (Arabidopsis thaliana) in response to Pseudomonas syringae pv tomato DC3000 (Pst). Ethylene biosynthesis is highly induced in both pathogen/microbe-associated molecular pattern (PAMP)-triggered immunity and effector-triggered immunity (ETI), and the induction is potentiated by salicylic acid (SA) pretreatment. In addition, Pst actively suppresses PAMP-triggered ethylene induction in a type III secretion system-dependent manner. SA potentiation of ethylene induction is dependent mostly on MITOGEN-ACTIVATED PROTEIN KINASE6 (MPK6) and MPK3 and their downstream ACS2 and ACS6, two type I isoforms of 1-aminocyclopropane-1-carboxylic acid synthases (ACSs). ACS7, a type III ACS whose expression is enhanced by SA pretreatment, is also involved. Pst expressing the avrRpt2 effector gene (Pst-avrRpt2), which is capable of triggering ETI, induces a higher level of ethylene production, and the elevated portion is dependent on SALICYLIC ACID INDUCTION DEFICIENT2 and NONEXPRESSER OF PATHOGENESIS-RELATED GENE1, two key players in SA biosynthesis and signaling. High-order ACS mutants with reduced ethylene induction are more susceptible to both Pst and Pst-avrRpt2, demonstrating a positive role of ethylene in plant bacterial resistance mediated by both PAMP-triggered immunity and ETI. © 2015 American Society of Plant Biologists. All Rights Reserved.

The Noise Level Optimization for Induction Magnetometer of SEP System

NASA Astrophysics Data System (ADS)

Zhu, W.; Fang, G.

2011-12-01

The Surface Electromagnetic Penetration (SEP) System, subsidized by the SinoProbe Plan in China, is designed for 3D conductivity imaging in geophysical mineral exploration, underground water distribution exploration, oil and gas reservoir exploration. Both the Controlled Source Audio Magnetotellurics (CSAMT) method and Magnetotellurics (MT) method can be surveyed by SEP system. In this article, an optimization design is introduced, which can minimize the noise level of the induction magnetometer for SEP system magnetic field's acquisition. The induction magnetometer transfers the rate of the magnetic field's change to voltage signal by induction coil, and amplified it by Low Noise Amplifier The noise parts contributed to the magnetometer are: the coil's thermal noise, the equivalent input voltage and current noise of the pre-amplifier. The coil's thermal noise is decided by coil's DC resistance. The equivalent input voltage and current noise of the pre-amplifier depend on the amplifier's type and DC operation condition. The design here optimized the DC operation point of pre-amplifier, adjusted the DC current source, and realized the minimum of total noise level of magnetometer. The calculation and test results show that: the total noise is about 1pT/√Hz, the thermal noise of coils is 1.7nV/√Hz, the preamplifier equivalent input voltage and current noise is 3nV/ √Hz and 0.1pA/√Hz, the weight of the magnetometer is 4.5kg and meet the requirement of SEP system.

An Induction Heating Method with Traveling Magnetic Field for Long Structure Metal

NASA Astrophysics Data System (ADS)

Sekine, Takamitsu; Tomita, Hideo; Obata, Shuji; Saito, Yukio

A novel dismantlable adhesion method for recycling operation of interior materials is proposed. This method is applied a high frequency induction heating and a thermoplastic adhesive. For an adhesion of interior material to long steel stud, a conventional spiral coil as like IH cooking heater gives inadequateness for uniform heating to the stud. Therefore, we have proposed an induction heating method with traveling magnetic field for perfect long structures bonding. In this paper, we describe on the new adhesion method using the 20kHz, three-phase 200V inverter and linear induction coil. From induction heating characteristics to thin steel plates and long studs, the method is cleared the usefulness for uniform heating to long structures.

Popperian and Inductivist Views of Science

ERIC Educational Resources Information Center

Fraser, Barry J.

1977-01-01

Illustrates that a view of the nature of science is dependent upon underlying assumptions concerning scientific proof. Compares the inductive view of science with the non-inductive viewpoint of Karl Popper. (CP)

Induction Mapping of the 3D-Modulated Spin Texture of Skyrmions in Thin Helimagnets

NASA Astrophysics Data System (ADS)

Schneider, S.; Wolf, D.; Stolt, M. J.; Jin, S.; Pohl, D.; Rellinghaus, B.; Schmidt, M.; Büchner, B.; Goennenwein, S. T. B.; Nielsch, K.; Lubk, A.

2018-05-01

Envisaged applications of Skyrmions in magnetic memory and logic devices crucially depend on the stability and mobility of these topologically nontrivial magnetic textures in thin films. We present for the first time quantitative maps of the magnetic induction that provide evidence for a 3D modulation of the Skyrmionic spin texture. The projected in-plane magnetic induction maps as determined from in-line and off-axis electron holography carry the clear signature of Bloch Skyrmions. However, the magnitude of this induction is much smaller than the values expected for homogeneous Bloch Skyrmions that extend throughout the thickness of the film. This finding can only be understood if the underlying spin textures are modulated along the out-of-plane z direction. The projection of (the in-plane magnetic induction of) helices is further found to exhibit thickness-dependent lateral shifts, which show that this z modulation is accompanied by an (in-plane) modulation along the x and y directions.

In Vivo Visualization of Bacterial Colonization, Antigen Expression, and Specific T-Cell Induction following Oral Administration of Live Recombinant Salmonella enterica Serovar Typhimurium

PubMed Central

Bumann, Dirk

2001-01-01

Live attenuated Salmonella strains that express a foreign antigen are promising oral vaccine candidates. Numerous genetic modifications have been empirically tested, but their effects on immunogenicity are difficult to interpret since important in vivo properties of recombinant Salmonella strains such as antigen expression and localization are incompletely characterized and the crucial early inductive events of an immune response to the foreign antigen are not fully understood. Here, methods were developed to directly localize and quantitate the in situ expression of an ovalbumin model antigen in recombinant Salmonella enterica serovar Typhimurium using two-color flow cytometry and confocal microscopy. In parallel, the in vivo activation, blast formation, and division of ovalbumin-specific CD4+ T cells were followed using a well-characterized transgenic T-cell receptor mouse model. This combined approach revealed a biphasic induction of ovalbumin-specific T cells in the Peyer's patches that followed the local ovalbumin expression of orally administered recombinant Salmonella cells in a dose- and time-dependent manner. Interestingly, intact Salmonella cells and cognate T cells seemed to remain in separate tissue compartments throughout induction, suggesting a transport of killed Salmonella cells from the colonized subepithelial dome area to the interfollicular inductive sites. The findings of this study will help to rationally optimize recombinant Salmonella strains as efficacious live antigen carriers for oral vaccination. PMID:11402006

Aromatase Inhibitor-Associated Bone Fractures: A Case-Cohort GWAS and Functional Genomics

PubMed Central

Liu, Mohan; Goss, Paul E.; Ingle, James N.; Kubo, Michiaki; Furukawa, Yoichi; Batzler, Anthony; Jenkins, Gregory D.; Carlson, Erin E.; Nakamura, Yusuke; Schaid, Daniel J.; Chapman, Judy-Anne W.; Shepherd, Lois E.; Ellis, Matthew J.; Khosla, Sundeep; Wang, Liewei

2014-01-01

Bone fractures are a major consequence of osteoporosis. There is a direct relationship between serum estrogen concentrations and osteoporosis risk. Aromatase inhibitors (AIs) greatly decrease serum estrogen levels in postmenopausal women, and increased incidence of fractures is a side effect of AI therapy. We performed a discovery case-cohort genome-wide association study (GWAS) using samples from 1071 patients, 231 cases and 840 controls, enrolled in the MA.27 breast cancer AI trial to identify genetic factors involved in AI-related fractures, followed by functional genomic validation. Association analyses identified 20 GWAS single nucleotide polymorphism (SNP) signals with P < 5E-06. After removal of signals in gene deserts and those composed entirely of imputed SNPs, we applied a functional validation “decision cascade” that resulted in validation of the CTSZ-SLMO2-ATP5E, TRAM2-TMEM14A, and MAP4K4 genes. These genes all displayed estradiol (E2)-dependent induction in human fetal osteoblasts transfected with estrogen receptor-α, and their knockdown altered the expression of known osteoporosis-related genes. These same genes also displayed SNP-dependent variation in E2 induction that paralleled the SNP-dependent induction of known osteoporosis genes, such as osteoprotegerin. In summary, our case-cohort GWAS identified SNPs in or near CTSZ-SLMO2-ATP5E, TRAM2-TMEM14A, and MAP4K4 that were associated with risk for bone fracture in estrogen receptor-positive breast cancer patients treated with AIs. These genes displayed E2-dependent induction, their knockdown altered the expression of genes related to osteoporosis, and they displayed SNP genotype-dependent variation in E2 induction. These observations may lead to the identification of novel mechanisms associated with fracture risk in postmenopausal women treated with AIs. PMID:25148458

Induction of Shiga Toxin-Encoding Prophage by Abiotic Environmental Stress in Food.

PubMed

Fang, Yuan; Mercer, Ryan G; McMullen, Lynn M; Gänzle, Michael G

2017-10-01

The prophage-encoded Shiga toxin is a major virulence factor in Stx-producing Escherichia coli (STEC). Toxin production and phage production are linked and occur after induction of the RecA-dependent SOS response. However, food-related stress and Stx-prophage induction have not been studied at the single-cell level. This study investigated the effects of abiotic environmental stress on stx expression by single-cell quantification of gene expression in STEC O104:H4 Δ stx2 :: gfp :: amp r In addition, the effect of stress on production of phage particles was determined. The lethality of stressors, including heat, HCl, lactic acid, hydrogen peroxide, and high hydrostatic pressure, was selected to reduce cell counts by 1 to 2 log CFU/ml. The integrity of the bacterial membrane after exposure to stress was measured by propidium iodide (PI). The fluorescent signals of green fluorescent protein (GFP) and PI were quantified by flow cytometry. The mechanism of prophage induction by stress was evaluated by relative gene expression of recA and cell morphology. Acid (pH < 3.5) and H 2 O 2 (2.5 mM) induced the expression of stx 2 in about 18% and 3% of the population, respectively. The mechanism of prophage induction by acid differs from that of induction by H 2 O 2 H 2 O 2 induction but not acid induction corresponded to production of infectious phage particles, upregulation of recA , and cell filamentation. Pressure (200 MPa) or heat did not induce the Stx2-encoding prophage (Stx2-prophage). Overall, the quantification method developed in this study allowed investigation of prophage induction and physiological properties at the single-cell level. H 2 O 2 and acids mediate different pathways to induce Stx2-prophage. IMPORTANCE Induction of the Stx-prophage in STEC results in production of phage particles and Stx and thus relates to virulence as well as the transduction of virulence genes. This study developed a method for a detection of the induction of Stx-prophages at the single-cell level; membrane permeability and an indication of SOS response to environmental stress were additionally assessed. H 2 O 2 and mitomycin C induced expression of the prophage and activated a SOS response. In contrast, HCl and lactic acid induced the Stx-prophage but not the SOS response. The lifestyle of STEC exposes the organism to intestinal and extraintestinal environments that impose oxidative and acid stress. A more thorough understanding of the influence of food processing-related stressors on Stx-prophage expression thus facilitates control of STEC in food systems by minimizing prophage induction during food production and storage. Copyright © 2017 American Society for Microbiology.

Induction of Shiga Toxin-Encoding Prophage by Abiotic Environmental Stress in Food

PubMed Central

Fang, Yuan; Mercer, Ryan G.; McMullen, Lynn M.

2017-01-01

ABSTRACT The prophage-encoded Shiga toxin is a major virulence factor in Stx-producing Escherichia coli (STEC). Toxin production and phage production are linked and occur after induction of the RecA-dependent SOS response. However, food-related stress and Stx-prophage induction have not been studied at the single-cell level. This study investigated the effects of abiotic environmental stress on stx expression by single-cell quantification of gene expression in STEC O104:H4 Δstx2::gfp::ampr. In addition, the effect of stress on production of phage particles was determined. The lethality of stressors, including heat, HCl, lactic acid, hydrogen peroxide, and high hydrostatic pressure, was selected to reduce cell counts by 1 to 2 log CFU/ml. The integrity of the bacterial membrane after exposure to stress was measured by propidium iodide (PI). The fluorescent signals of green fluorescent protein (GFP) and PI were quantified by flow cytometry. The mechanism of prophage induction by stress was evaluated by relative gene expression of recA and cell morphology. Acid (pH < 3.5) and H2O2 (2.5 mM) induced the expression of stx2 in about 18% and 3% of the population, respectively. The mechanism of prophage induction by acid differs from that of induction by H2O2. H2O2 induction but not acid induction corresponded to production of infectious phage particles, upregulation of recA, and cell filamentation. Pressure (200 MPa) or heat did not induce the Stx2-encoding prophage (Stx2-prophage). Overall, the quantification method developed in this study allowed investigation of prophage induction and physiological properties at the single-cell level. H2O2 and acids mediate different pathways to induce Stx2-prophage. IMPORTANCE Induction of the Stx-prophage in STEC results in production of phage particles and Stx and thus relates to virulence as well as the transduction of virulence genes. This study developed a method for a detection of the induction of Stx-prophages at the single-cell level; membrane permeability and an indication of SOS response to environmental stress were additionally assessed. H2O2 and mitomycin C induced expression of the prophage and activated a SOS response. In contrast, HCl and lactic acid induced the Stx-prophage but not the SOS response. The lifestyle of STEC exposes the organism to intestinal and extraintestinal environments that impose oxidative and acid stress. A more thorough understanding of the influence of food processing-related stressors on Stx-prophage expression thus facilitates control of STEC in food systems by minimizing prophage induction during food production and storage. PMID:28778890

Primula auriculata Extracts Exert Cytotoxic and Apoptotic Effects against HT-29 Human Colon Adenocarcinoma Cells

PubMed Central

Behzad, Sahar; Ebrahim, Karim; Mosaddegh, Mahmoud; Haeri, Ali

2016-01-01

Primula auriculata (Tootia) is one of the most important local medicinal plants in Hamedan district, Iran. To investigate cytotoxicity and apoptosis induction of crude methanolic extract and different fraction of it, we compared several methods on HT-29 human colon Adenocarcinoma cells. Cancer cell proliferation was measured by 3-(4, 5‑dimethylthiazolyl)2, 5‑diphenyl‑tetrazolium bromide (MTT) assay and apoptosis induction was analyzed by fluorescence microscopy (acridin orange/ethidium bromide, annexin V/propidium iodide staining, TUNEL assay and Caspase-3 activity assay). Crude methanolic extract (CM) inhibited the growth of malignant cells in a dose-dependent manner. Among solvent fractions, the dichloromethane fraction (CF) was found to be the most toxic compared to other fractions. With double staining methods, high percentage of 40 µg/mL of (CM) and (CF) treated cells exhibited typical characteristics of apoptotic cells. Apoptosis induction was also revealed by apoptotic fragmentation of nuclear DNA and activation of caspas-3 in treated cells. These findings indicate that crude methanolic extract and dichloromethan fraction of P.auriculata induced apoptosis and inhibited proliferation in colon cancer cells and could be used as a source for new lead structures in drug design to combat colon cancer. PMID:27610172

The dynamical conductance of graphene tunnelling structures.

PubMed

Zhang, Huan; Chan, K S; Lin, Zijing

2011-12-16

The dynamical conductances of graphene tunnelling structures were numerically calculated using the scattering matrix method with the interaction effect included in a phenomenological approach. The overall single-barrier dynamical conductance is capacitative. Transmission resonances in the single-barrier structure lead to dips in the capacitative imaginary part of the response. This is different from the ac responses of typical semiconductor nanostructures, where transmission resonances usually lead to inductive peaks. The features of the dips depend on the Fermi energy. When the Fermi energy is below half of the barrier height, the dips are sharper. When the Fermi energy is higher than half of the barrier height, the dips are broader. Inductive behaviours can be observed in a double-barrier structure due to the resonances formed by reflection between the two barriers.

Inductance and resistance measurement method for vessel detection and coil powering in all-surface inductive heating systems composed of outer squircle coils

NASA Astrophysics Data System (ADS)

Kilic, Veli Tayfun; Unal, Emre; Demir, Hilmi Volkan

2017-05-01

In this work, we investigate a method proposed for vessel detection and coil powering in an all-surface inductive heating system composed of outer squircle coils. Besides conventional circular coils, coils with different shapes such as outer squircle coils are used for and enable efficient all-surface inductive heating. Validity of the method, which relies on measuring inductance and resistance values of a loaded coil at different frequencies, is experimentally demonstrated for a coil with shape different from conventional circular coil. Simple setup was constructed with a small coil to model an all-surface inductive heating system. Inductance and resistance maps were generated by measuring coil's inductance and resistance values at different frequencies loaded by a plate made of different materials and located at various positions. Results show that in an induction hob for various coil geometries it is possible to detect a vessel's presence, to identify its material type and to specify its position on the hob surface by considering inductance and resistance of the coil measured on at least two different frequencies. The studied method is important in terms of enabling safe, efficient and user flexible heating in an all-surface inductive heating system by automatically detecting the vessel's presence and powering on only the coils that are loaded by the vessel with predetermined current levels.

Dendritic spine dynamics in synaptogenesis after repeated LTP inductions: Dependence on pre-existing spine density

PubMed Central

Oe, Yuki; Tominaga-Yoshino, Keiko; Hasegawa, Sho; Ogura, Akihiko

2013-01-01

Not only from our daily experience but from learning experiments in animals, we know that the establishment of long-lasting memory requires repeated practice. However, cellular backgrounds underlying this repetition-dependent consolidation of memory remain largely unclear. We reported previously using organotypic slice cultures of rodent hippocampus that the repeated inductions of LTP (long-term potentiation) lead to a slowly developing long-lasting synaptic enhancement accompanied by synaptogenesis distinct from LTP itself, and proposed this phenomenon as a model system suitable for the analysis of the repetition-dependent consolidation of memory. Here we examined the dynamics of individual dendritic spines after repeated LTP-inductions and found the existence of two phases in the spines' stochastic behavior that eventually lead to the increase in spine density. This spine dynamics occurred preferentially in the dendritic segments having low pre-existing spine density. Our results may provide clues for understanding the cellular bases underlying the repetition-dependent consolidation of memory. PMID:23739837

HOXA9 Methylation by PRMT5 Is Essential for Endothelial Cell Expression of Leukocyte Adhesion Molecules

PubMed Central

Bandyopadhyay, Smarajit; Harris, Daniel P.; Adams, Gregory N.; Lause, Gregory E.; McHugh, Anne; Tillmaand, Emily G.; Money, Angela; Willard, Belinda; Fox, Paul L.

2012-01-01

The induction of proinflammatory proteins in stimulated endothelial cells (EC) requires activation of multiple transcription programs. The homeobox transcription factor HOXA9 has an important regulatory role in cytokine induction of the EC-leukocyte adhesion molecules (ELAM) E-selectin and vascular cell adhesion molecule 1 (VCAM-1). However, the mechanism underlying stimulus-dependent activation of HOXA9 is completely unknown. Here, we elucidate the molecular mechanism of HOXA9 activation by tumor necrosis factor alpha (TNF-α) and show an unexpected requirement for arginine methylation by protein arginine methyltransferase 5 (PRMT5). PRMT5 was identified as a TNF-α-dependent binding partner of HOXA9 by mass spectrometry. Small interfering RNA (siRNA)-mediated depletion of PRMT5 abrogated stimulus-dependent HOXA9 methylation with concomitant loss in E-selectin or VCAM-1 induction. Chromatin immunoprecipitation analysis revealed that PRMT5 is recruited to the E-selectin promoter following transient HOXA9 binding to its cognate recognition sequence. PRMT5 induces symmetric dimethylation of Arg140 on HOXA9, an event essential for E-selectin induction. In summary, PRMT5 is a critical coactivator component in a newly defined, HOXA9-containing transcription complex. Moreover, stimulus-dependent methylation of HOXA9 is essential for ELAM expression during the EC inflammatory response. PMID:22269951

Chromosomal instability induced by heavy ion irradiation

NASA Technical Reports Server (NTRS)

Limoli, C. L.; Ponnaiya, B.; Corcoran, J. J.; Giedzinski, E.; Morgan, W. F.

2000-01-01

PURPOSE: To establish the dose-response relationship for the induction of chromosomal instability in GM10115 cells exposed to high-energy iron ions (1 GeV/nucleon, mean LET 146 keV/microm) and gold ions (11 GeV/nucleon, mean LET 1450 keV/microm). Past work has established that sparsely ionizing X-rays can induce a long-lived destabilization of chromosomes in a dose-dependent manner at an incidence of approximately 3% per gray. The present investigation assesses the capacity of High-Z and High-energy (HZE) particles to elicit this same endpoint. MATERIALS AND METHODS: Clonal populations derived from single progenitor cells surviving heavy-ion irradiation were analyzed cytogenetically to identify those clones showing a persistent destablization of chromosomes. RESULTS: Dose-response data, with a particular emphasis at low dose (< 1.0 Gy), indicate a frequency of approximately 4% per gray for the induction of chromosomal instability in clones derived from single progenitor cells surviving exposure to iron ions. The induction of chromosomal instability by gold ions was, however, less responsive to applied dose, as the observed incidence of this phenotype varied from 0 to 10% over 1-8 Gy. Both iron and gold ions gave dose-dependent increases in the yield of chromosomal aberrations (both chromosome- and chromatid-type) measured at the first mitosis following irradiation, as well as shoulderless survival curves having D0=0.87 and 1.1 Gy respectively. CONCLUSIONS: Based on the present dose-response data, the relative biological effectiveness of iron ions is 1.3 for the induction of chromosomal instability, and this indicates that heavy ions are only slightly more efficient than X-rays at eliciting this delayed phenotype.

Monitoring transients in low inductance circuits

DOEpatents

Guilford, R.P.; Rosborough, J.R.

1985-10-21

The instant invention relates to methods of and apparatus for monitoring transients in low inductance circuits and to a probe utilized to practice said method and apparatus. More particularly, the instant invention relates to methods of and apparatus for monitoring low inductance circuits, wherein the low inductance circuits include a pair of flat cable transmission lines. The instant invention is further directed to a probe for use in monitoring pairs of flat cable transmission lines.

Methods for inducing alcohol craving in individuals with comorbid alcohol dependence and posttraumatic stress disorder: Behavioral and physiological outcomes

PubMed Central

Kwako, L. E.; Schwandt, M. L.; Sells, J. R.; Ramchandani, V. A.; George, D. T.; Sinha, R.; Heilig, M.

2014-01-01

Rationale Alcohol addiction is a chronic relapsing disorder that presents a substantial public health problem, and is frequently comorbid with posttraumatic stress disorder (PTSD). Craving for alcohol is a predictor of relapse to alcohol use, and is triggered by cues associated with alcohol and trauma. Identification of reliable and valid laboratory methods for craving induction is an important objective for alcoholism and PTSD research. Objectives The present study compares two methods for induction of craving via stress and alcohol cues in individuals with comorbid alcohol dependence (AD) and PTSD: the combined Trier Social Stress Test and cue reactivity paradigm (Trier/CR), and a guided imagery (Scripts) paradigm. Outcomes include self-reported measures of craving, stress, and anxiety as well as endocrine measures. Methods Subjects were 52 individuals diagnosed with comorbid AD and PTSD seeking treatment at the NIAAA inpatient research facility. They participated in a four week inpatient study of the efficacy of a NK1 antagonist to treat comorbid AD and PTSD, and which included the two challenge procedures. Results Both the Trier/CR and Scripts induced craving for alcohol, as well as elevated levels of subjective distress and anxiety. The Trier/CR yielded significant increases in ACTH and cortisol, while the Scripts did not. Conclusions Both paradigms are effective laboratory means of inducing craving for alcohol. Further research is warranted to better understand the mechanisms behind craving induced by stress vs. alcohol cues, as well as to understand the impact of comorbid PTSD and AD on craving. PMID:24806358

On the Effects of Training Inductive Reasoning: How Far Does It Transfer and How Long Do the Effects Persist?

ERIC Educational Resources Information Center

Tomic, Welko; Klauer, Karl Josef

1996-01-01

Reports on two training experiments in which it was expected that training in inductive reasoning would transfer to intelligence tests measuring inductive reasoning and on mathematics performance. Shows that transfer on intelligence tests as well as on mathematics performance was linearly dependent on the amount of prior training. (DSK)

Separation of Electric Fields Into Potential and Inductive Parts, and Implications for Radial Diffusion

NASA Astrophysics Data System (ADS)

Chan, A. A.; Ilie, R.; Elkington, S. R.; Albert, J.; Huie, W.

2017-12-01

It has been traditional to separate radiation belt radial-diffusion coefficients into two contributions: an "electrostatic" diffusion coefficient, which is assumed to be due to a potential (non-inductive) electric field, and an "electromagnetic" diffusion coefficient , which is assumed to be due to the combined effect of an inductive electric field and the corresponding time-dependent magnetic field. One difficulty in implementing this separation when using magnetospheric fields obtained from measurements, or from MHD simulations, is that only the total electric field is given; the separation of the electric field into potential and inductive parts is not readily available. In this work we separate the electric field using a numerical method based on the Helmholtz decomposition of the total motional electric field calculated by the BATS-R-US MHD code. The inner boundary for the electric potential is based on the Ridley Ionospheric Model solution and we assume floating boundary conditions in the solar wind. Using different idealized solar wind drivers, including a solar wind density that is oscillating at a single frequency or with a broad spectrum of frequencies, we calculate potential and inductive electric fields, electric and magnetic power spectral densities, and corresponding radial diffusion coefficients. Simulations driven by idealized solar wind conditions show a clear separation of the potential and inductive contributions to the power spectral densities and diffusion coefficients. Simulations with more realistic solar wind drivers are underway to better assess the use of electrostatic and electromagnetic diffusion coefficients in understanding ULF wave-particle interactions in Earth's radiation belts.

Human HepaRG Cells can be Cultured in Hanging-drop Plates for Cytochrome P450 Induction and Function Assays.

PubMed

Murayama, Norie; Usui, Takashi; Slawny, Nicky; Chesné, Christophe; Yamazaki, Hiroshi

2015-01-01

Recent guidance/guidelines for industry recommend that cytochrome P450 induction can be assessed using human hepatocyte enzyme activity and/or mRNA levels to evaluate potential drug- drug interactions. To evaluate time-dependent cytochrome P450 induction precisely, induction of CYP1A2, CYP2B6, and CYP3A4 mRNA was confirmed (>2-fold) by the treatment with omeprazole, phenobarbital, and rifampicin, respectively, for 24 or 48 h on day 3 from the start of culture. After 24 h, the fold induction of CYP1A2 with 3.6 and 1.8x10(4) HepaRG cells per well was lower than that for 7.2x10(4) cells. CYP1A2 induction levels at 24 h were higher than those after 48 h. In contrast, higher CYP2B6 inductions were confirmed after 48 h exposure than after 24 h, independent of the number of cells per well. To help reduce the use of human cryopreserved hepatocytes, typical P450-dependent enzyme activities were investigated in human HepaRG cells cultured in commercial hanging-drop plates. Newly designed 96-well hanging-drop plates were capable of maintaining human CYP3A-dependent midazolam hydroxylation activities for up to 4 days using only 10% of the recommended initial 7.2x10(4) cells per well. Favorable HepaRG function using hanging-drop plates was confirmed by detecting 1'- hydroxymidazolam O-glucuronide on day 3, suggesting an improvement over traditional control plates in which this metabolite can be detected for 24-well plates. These results suggest that the catalytic function and/or induction of CYP1A2, CYP2B6, and CYP3A4 can be readily assessed with reduced numbers of starting HepaRG cells cultured in three-dimensional cultures in drops prepared with hanging-drop plates.

Time-dependent pharmacokinetics of dexamethasone and its efficacy in human breast cancer xenograft mice: a semi-mechanism-based pharmacokinetic/pharmacodynamic model.

PubMed

Li, Jian; Chen, Rong; Yao, Qing-Yu; Liu, Sheng-Jun; Tian, Xiu-Yun; Hao, Chun-Yi; Lu, Wei; Zhou, Tian-Yan

2018-03-01

Dexamethasone (DEX) is the substrate of CYP3A. However, the activity of CYP3A could be induced by DEX when DEX was persistently administered, resulting in auto-induction and time-dependent pharmacokinetics (pharmacokinetics with time-dependent clearance) of DEX. In this study we investigated the pharmacokinetic profiles of DEX after single or multiple doses in human breast cancer xenograft nude mice and established a semi-mechanism-based pharmacokinetic/pharmacodynamic (PK/PD) model for characterizing the time-dependent PK of DEX as well as its anti-cancer effect. The mice were orally given a single or multiple doses (8 mg/kg) of DEX, and the plasma concentrations of DEX were assessed using LC-MS/MS. Tumor volumes were recorded daily. Based on the experimental data, a two-compartment model with first order absorption and time-dependent clearance was established, and the time-dependence of clearance was modeled by a sigmoid E max equation. Moreover, a semi-mechanism-based PK/PD model was developed, in which the auto-induction effect of DEX on its metabolizing enzyme CYP3A was integrated and drug potency was described using an E max equation. The PK/PD model was further used to predict the drug efficacy when the auto-induction effect was or was not considered, which further revealed the necessity of adding the auto-induction effect into the final PK/PD model. This study established a semi-mechanism-based PK/PD model for characterizing the time-dependent pharmacokinetics of DEX and its anti-cancer effect in breast cancer xenograft mice. The model may serve as a reference for DEX dose adjustments or optimization in future preclinical or clinical studies.

p53-dependent inhibition of TrxR1 contributes to the tumor-specific induction of apoptosis by RITA.

PubMed

Hedström, Elisabeth; Eriksson, Sofi; Zawacka-Pankau, Joanna; Arnér, Elias S J; Selivanova, Galina

2009-11-01

Thioredoxin reductase 1 (TrxR1) is a key regulator in many redox-dependent cellular pathways, and is often overexpressed in cancer. Several studies have identified TrxR1 as a potentially important target for anticancer therapy. The low molecular weight compound RITA (NSC 652287) binds p53 and induces p53-dependent apoptosis. Here we found that RITA also targets TrxR1 by non-covalent binding, followed by inhibition of its activity in vitro and by inhibition of TrxR activity in cancer cells. Interestingly, a novel approximately 130 kDa form of TrxR1, presumably representing a stable covalently linked dimer, and an increased generation of reactive oxygen species (ROS) were induced by RITA in cancer cells in a p53-dependent manner. Similarly, the gold-based TrxR inhibitor auranofin induced apoptosis related to oxidative stress, but independently of p53 and without apparent induction of the approximately 130 kDa form of TrxR1. In contrast to the effects observed in cancer cells, RITA did not inhibit TrxR or ROS formation in normal fibroblasts (NHDF). The inhibition of TrxR1 can sensitize tumor cells to agents that induce oxidative stress and may directly trigger cell death. Thus, our results suggest that a unique p53-dependent effect of RITA on TrxR1 in cancer cells might synergize with p53-dependent induction of pro-apoptotic genes and oxidative stress, thereby leading to a robust induction of cancer cell death, without affecting non-transformed cells.

SESN2/sestrin 2 induction-mediated autophagy and inhibitory effect of isorhapontigenin (ISO) on human bladder cancers.

PubMed

Liang, Yuguang; Zhu, Junlan; Huang, Haishan; Xiang, Daimin; Li, Yang; Zhang, Dongyun; Li, Jingxia; Wang, Yulei; Jin, Honglei; Jiang, Guosong; Liu, Zeyuan; Huang, Chuanshu

2016-08-02

Isorhapontigenin (ISO) is a new derivative of stilbene isolated from the Chinese herb Gnetum cleistostachyum. Our recent studies have revealed that ISO treatment at doses ranging from 20 to 80 μM triggers apoptosis in multiple human cancer cell lines. In the present study, we evaluated the potential effect of ISO on autophagy induction. We found that ISO treatment at sublethal doses induced autophagy effectively in human bladder cancer cells, which contributed to the inhibition of anchorage-independent growth of cancer cells. In addition, our studies revealed that ISO-mediated autophagy induction occurred in a SESN2 (sestrin 2)-dependent and BECN1 (Beclin 1, autophagy related)-independent manner. Furthermore, we identified that ISO treatment induced SESN2 expression via a MAPK8/JNK1 (mitogen-activated protein kinase 8)/JUN-dependent mechanism, in which ISO triggered MAPK8-dependent JUN activation and facilitated the binding of JUN to a consensus AP-1 binding site in the SESN2 promoter region, thereby led to a significant transcriptional induction of SESN2. Importantly, we found that SESN2 expression was dramatically downregulated or even lost in human bladder cancer tissues as compared to their paired adjacent normal tissues. Collectively, our results demonstrate that ISO treatment induces autophagy and inhibits bladder cancer growth through MAPK8-JUN-dependent transcriptional induction of SESN2, which provides a novel mechanistic insight into understanding the inhibitory effect of ISO on bladder cancers and suggests that ISO might act as a promising preventive and/or therapeutic drug against human bladder cancer.

Long-Acting Injectable Naltrexone Induction: A Randomized Trial of Outpatient Opioid Detoxification With Naltrexone Versus Buprenorphine.

PubMed

Sullivan, Maria; Bisaga, Adam; Pavlicova, Martina; Choi, C Jean; Mishlen, Kaitlyn; Carpenter, Kenneth M; Levin, Frances R; Dakwar, Elias; Mariani, John J; Nunes, Edward V

2017-05-01

At present there is no established optimal approach for transitioning opioid-dependent adults to extended-release injection naltrexone (XR-naltrexone) while preventing relapse. The authors conducted a trial examining the efficacy of two methods of outpatient opioid detoxification for induction to XR-naltrexone. Participants were 150 opioid-dependent adults randomly assigned 2:1 to one of two outpatient detoxification regimens, naltrexone-assisted detoxification or buprenorphine-assisted detoxification, followed by an injection of XR-naltrexone. Naltrexone-assisted detoxification lasted 7 days and included a single day of buprenorphine followed by ascending doses of oral naltrexone along with clonidine and other adjunctive medications. Buprenorphine-assisted detoxification included a 7-day buprenorphine taper followed by a week-long delay before administration of XR-naltrexone, consistent with official prescribing information for XR-naltrexone. Participants from both groups received behavioral therapy focused on medication adherence and a second dose of XR-naltrexone. Compared with participants in the buprenorphine-assisted detoxification condition, participants assigned to naltrexone-assisted detoxification were significantly more likely to be successfully inducted to XR-naltrexone (56.1% compared with 32.7%) and to receive the second injection at week 5 (50.0% compared with 26.9%). Both models adjusted for primary type of opioid use, route of opioid administration, and morphine equivalents at baseline. These results demonstrate the safety, efficacy, and tolerability of low-dose naltrexone, in conjunction with single-day buprenorphine dosing and adjunctive nonopioid medications, for initiating adults with opioid dependence to XR-naltrexone. This strategy offers a promising alternative to the high rates of attrition and relapse currently observed with agonist tapers in both inpatient and outpatient settings.

Sexual intercourse for cervical ripening and induction of labour.

PubMed

Kavanagh, J; Kelly, A J; Thomas, J

2001-01-01

The role of prostaglandins for cervical ripening and induction of labour has been examined extensively. Human semen is the biological source that is presumed to contain the highest prostaglandin concentration. The role of sexual intercourse in the initiation of labour is uncertain. The action of sexual intercourse in stimulating labour is unclear, it may in part be due to the physical stimulation of the lower uterine segment, or endogenous release of oxytocin as a result of orgasm or from the direct action of prostaglandins in semen. Furthermore nipple stimulation may be part of the process of initiation. This is one of a series of reviews of methods of cervical ripening and labour induction using standardised methodology. To determine the effects of sexual intercourse for third trimester cervical ripening or induction of labour in comparison with other methods of induction. The Cochrane Pregnancy and Childbirth Group trials register, the Cochrane Controlled Trials Register and bibliographies of relevant papers. Last searched: November 2000. (1) clinical trials comparing sexual intercourse for third trimester cervical ripening or labour induction with placebo/no treatment or other methods listed above it on a predefined list of labour induction methods; (2) random allocation to the treatment or control group; (3) adequate allocation concealment; (4) violations of allocated management not sufficient to materially affect conclusions; (5) clinically meaningful outcome measures reported; (6) data available for analysis according to the random allocation; (7) missing data insufficient to materially affect the conclusion. A strategy has been developed to deal with the large volume and complexity of trial data relating to labour induction. This involves a two-stage method of data extraction. There was one included study of 28 women which reported very limited data, from which no meaningful conclusions can be drawn. The role of sexual intercourse as a method of induction of labour is uncertain. Any future trials investigating sexual intercourse as a method of induction need to be of sufficient power to detect clinically relevant differences in standard outcomes. However, it may prove difficult to standardise sexual intercourse as an intervention to allow meaningful comparisons with other methods of induction of labour.

Electric characteristics of a surface barrier discharge with a plasma induction electrode

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

Alemskii, I. N.; Lelevkin, V. M.; Tokarev, A. V.

2006-07-15

Static and dynamic current-voltage and charge-voltage characteristics of a surface barrier discharge with a plasma induction electrode have been investigated experimentally. The dependences of the discharge current on both the gas pressure in the induction electrode tube and the winding pitch of the corona electrode, as well as of the discharge power efficiency on the applied voltage, have been measured.

The detection of brain oedema with frequency-dependent phase shift electromagnetic induction.

PubMed

González, César A; Rubinsky, Boris

2006-06-01

The spectroscopic distribution of inductive phase shift in the brain as a function of the relative volume of oedema was evaluated with theoretical and experimental methods in the frequency range 1 to 8 MHz. The theoretical study employed a simple mathematical model of electromagnetic induction in tissue and brain tissue data available from the literature to calculate the phase shift as a function of oedema in the bulk of the brain. Experimental data were generated from bulk measurements of ex vivo homogenized pig brain tissue mixed with various volumes of physiological saline in a volume sample typical of the human brain. There is good agreement between the analytical and the experimental results. Detectable changes in phase shift begin from a frequency of about 3 MHz to 4 MHz in the tested compositions and volume. The phase shift increases with frequency and fluid content. The results suggest that measuring phase shift in the bulk of the brain has the potential for becoming a robust means for non-contact detection of oedema in the brain.

Analysis of Instantaneous Attractive-Normal Force and Vertical Vibration Control of Combined-Levitation-and-Propulsion SLIM Vehicle

NASA Astrophysics Data System (ADS)

Yoshida, Takashi

Combined-levitation-and-propulsion single-sided linear induction motor (SLIM) vehicle can be levitated without any additional levitation system. When the vehicle runs, the attractive-normal force varies depending on the phase of primary current because of the short primary end effect. The ripple of the attractive-normal force causes the vertical vibration of the vehicle. In this paper, instantaneous attractive-normal force is analyzed by using space harmonic analysis method. And based on the analysis, vertical vibration control is proposed. The validity of the proposed control method is verified by numerical simulation.

Stimulus size dependence of hue changes induced by chromatic surrounds.

PubMed

Kellner, Christian Johannes; Wachtler, Thomas

2016-03-01

A chromatic surround induces a change in the perceived hue of a stimulus. This shift in hue depends on the chromatic difference between the stimulus and the surround. We investigated how chromatic induction varies with stimulus size and whether the size dependence depends on the surround hue. Subjects performed asymmetric matching of color stimuli with different sizes in surrounds of different chromaticities. Generally, induced hue shifts decreased with increasing stimulus size. This decrease was quantitatively different for different surround hues. However, when size effects were normalized to an overall induction strength, the chromatic specificity was largely reduced. The separability of inducer chromaticity and stimulus size suggests that these effects are mediated by different neural mechanisms.

Salicylic acid potentiates an agonist-dependent gain control that amplifies pathogen signals in the activation of defense mechanisms.

PubMed

Shirasu, K; Nakajima, H; Rajasekhar, V K; Dixon, R A; Lamb, C

1997-02-01

The phenylpropanoid-derived natural product salicylic acid (SA) plays a key role in disease resistance. However, SA administered in the absence of a pathogen is a paradoxically weak inductive signal, often requiring concentrations of 0.5 to 5 mM to induce acquired resistance or related defense mechanisms or to precondition signal systems. In contrast, endogenous SA accumulates to concentrations of < 70 microM at the site of attempted infection. Here, we show that although 10 to 100 microM SA had negligible effects when administered to soybean cell suspensions in the absence of a pathogen, physiological concentrations of SA markedly enhanced the induction of defense gene transcripts, H2O2 accumulation, and hypersensitive cell death by an avirulent strain of Pseudomonas syringae pv glycinea, with optimal effects being at approximately 50 microM. SA also synergistically enhanced H2O2 accumulation in response to the protein phosphatase type 2A inhibitor cantharidin in the absence of a pathogen. The synergistic effect of SA was potent, rapid, and insensitive to the protein synthesis inhibitor cycloheximide, and we conclude that SA stimulates an agonist-dependent gain control operating at an early step in the signal pathway for induction of the hypersensitive response. This fine control mechanism differs from previously described time-dependent, inductive coarse control mechanisms for SA action in the absence of a pathogen. Induction of H2O2 accumulation and hypersensitive cell death by avirulent P. s. glycinea was blocked by the phenylpropanoid synthesis inhibitor alpha-aminooxy-beta-phenylpropionic acid, and these responses could be rescued by exogenous SA. Because the agonist-dependent gain control operates at physiological levels of SA, we propose that rapid fine control signal amplification makes an important contribution to SA function in the induction of disease resistance mechanisms.

Excitation-transcription coupling via calcium/calmodulin-dependent protein kinase/ERK1/2 signaling mediates the coordinate induction of VGLUT2 and Narp triggered by a prolonged increase in glutamatergic synaptic activity.

PubMed

Doyle, Sukhjeevan; Pyndiah, Slovénie; De Gois, Stéphanie; Erickson, Jeffrey D

2010-05-07

Homeostatic scaling of glutamatergic and GABAergic transmission is triggered by prolonged alterations in synaptic neuronal activity. We have previously described a presynaptic mechanism for synaptic homeostasis and plasticity that involves scaling the level of vesicular glutamate (VGLUT1) and gamma-aminobutyric acid (GABA) (VGAT) transporter biosynthesis. These molecular determinants of vesicle filling and quantal size are regulated by neuronal activity in an opposite manner and bi-directionally. Here, we report that a striking induction of VGLUT2 mRNA and synaptic protein is triggered by a prolonged increase in glutamatergic synaptic activity in mature neocortical neuronal networks in vitro together with two determinants of inhibitory synaptic strength, the neuronal activity-regulated pentraxin (Narp), and glutamate decarboxylase (GAD65). Activity-dependent induction of VGLUT2 and Narp exhibits a similar intermediate-early gene response that is blocked by actinomycin D and tetrodotoxin, by inhibitors of ionotropic glutamate receptors and L-type voltage-gated calcium channels, and is dependent on downstream signaling via calmodulin, calcium/calmodulin-dependent protein kinase (CaMK) and extracellular signal-regulated kinase 1/2 (ERK1/2). The co-induction of VGLUT2 and Narp triggered by prolonged gamma-aminobutyric acid type A receptor blockade is independent of brain-derived nerve growth factor and TrkB receptor signaling. VGLUT2 protein induction occurs on a subset of cortically derived synaptic vesicles in excitatory synapses on somata and dendritic processes of multipolar GABAergic interneurons, recognized sites for the clustering of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate glutamate receptors by Narp. We propose that VGLUT2 and Narp induction by excitation-transcription coupling leads to increased glutamatergic transmission at synapses on GABAergic inhibitory feedback neurons as part of a coordinated program of Ca(2+)-signal transcription involved in mechanisms of homeostatic plasticity after prolonged hyperactivity.

LET and ion-species dependence for cell killing and mutation induction in normal human fibroblasts.

PubMed

Tsuruoka, Chizuru; Suzuki, Masao; Fujitaka, Kazunobu

2003-10-01

We have been studying LET and ion species dependence of RBE values in cell killing and mutation induction. Normal human skin fibroblasts were irradiated with heavy-ion beams such as carbon (290 Mev/u and 135 Mev/u), neon (230 Mev/u and 400 Mev/u), silicon (490 Mev/u) and iron (500 Mev/u) ion beams, generated by Heavy Ion Medical Accelerator in Chiba (HIMAC) at National Institute of Radiological Sciences (NIRS). Cell killing effect was detected as reproductive cell death using a colony formation assay. Mutation induction in hprt locus was detected to measure 6-thioguanine resistant colonies. The RBE-LET curves of cell killing and mutation induction were different each ion beam. So, we plotted RBE for cell killing and mutation induction as function of Z*2/beta2 instead of LET. RBE-Z*2/beta2 curves of cell killing indicated that the discrepancy of RBE-LET curves was reconciled each ion species. But RBE-Z*2/beta2 curves of mutation induction didn't corresponded between carbon- and silicon-ion beams. These results suggested that different biological endpoints may be suitable for different physical parameter, which represent the track structure of energy deposition of ion beams.

Comparative Study of Fault Diagnostic Methods in Voltage Source Inverter Fed Three Phase Induction Motor Drive

NASA Astrophysics Data System (ADS)

Dhumale, R. B.; Lokhande, S. D.

2017-05-01

Three phase Pulse Width Modulation inverter plays vital role in industrial applications. The performance of inverter demeans as several types of faults take place in it. The widely used switching devices in power electronics are Insulated Gate Bipolar Transistors (IGBTs) and Metal Oxide Field Effect Transistors (MOSFET). The IGBTs faults are broadly classified as base or collector open circuit fault, misfiring fault and short circuit fault. To develop consistency and performance of inverter, knowledge of fault mode is extremely important. This paper presents the comparative study of IGBTs fault diagnosis. Experimental set up is implemented for data acquisition under various faulty and healthy conditions. Recent methods are executed using MATLAB-Simulink and compared using key parameters like average accuracy, fault detection time, implementation efforts, threshold dependency, and detection parameter, resistivity against noise and load dependency.

INS-1 Cells Undergoing Caspase-Dependent Apoptosis Enhance the Regenerative Capacity of Neighboring Cells

PubMed Central

Bonner, Caroline; Bacon, Siobhán; Concannon, Caoimhín G.; Rizvi, Syed R.; Baquié, Mathurin; Farrelly, Angela M.; Kilbride, Seán M.; Dussmann, Heiko; Ward, Manus W.; Boulanger, Chantal M.; Wollheim, Claes B.; Graf, Rolf; Byrne, Maria M.; Prehn, Jochen H.M.

2010-01-01

OBJECTIVE In diabetes, β-cell mass is not static but in a constant process of cell death and renewal. Inactivating mutations in transcription factor 1 (tcf-1)/hepatocyte nuclear factor1a (hnf1a) result in decreased β-cell mass and HNF1A–maturity onset diabetes of the young (HNF1A-MODY). Here, we investigated the effect of a dominant-negative HNF1A mutant (DN-HNF1A) induced apoptosis on the regenerative capacity of INS-1 cells. RESEARCH DESIGN AND METHODS DN-HNF1A was expressed in INS-1 cells using a reverse tetracycline-dependent transactivator system. Gene(s)/protein(s) involved in β-cell regeneration were investigated by real-time quantitative RT-PCR, Western blotting, and immunohistochemistry. Pancreatic stone protein/regenerating protein (PSP/reg) serum levels in human subjects were detected by enzyme-linked immunosorbent assay. RESULTS We detected a prominent induction of PSP/reg at the gene and protein level during DN-HNF1A–induced apoptosis. Elevated PSP/reg levels were also detected in islets of transgenic HNF1A-MODY mice and in the serum of HNF1A-MODY patients. The induction of PSP/reg was glucose dependent and mediated by caspase activation during apoptosis. Interestingly, the supernatant from DN-HNF1A–expressing cells, but not DN-HNF1A–expressing cells treated with zVAD.fmk, was sufficient to induce PSP/reg gene expression and increase cell proliferation in naïve, untreated INS-1 cells. Further experiments demonstrated that annexin-V–positive microparticles originating from apoptosing INS-1 cells mediated the induction of PSP/reg. Treatment with recombinant PSP/reg reversed the phenotype of DN-HNF1A–induced cells by stimulating cell proliferation and increasing insulin gene expression. CONCLUSIONS Our results suggest that apoptosing INS-1 cells shed microparticles that may stimulate PSP/reg induction in neighboring cells, a mechanism that may facilitate the recovery of β-cell mass in HNF1A-MODY. PMID:20682686

RsbV-Independent Induction of the SigB-Dependent General Stress Regulon of Bacillus subtilis during Growth at High Temperature

PubMed Central

Holtmann, Gudrun; Brigulla, Matthias; Steil, Leif; Schütz, Alexandra; Barnekow, Karsta; Völker, Uwe; Bremer, Erhard

2004-01-01

General stress proteins protect Bacillus subtilis cells against a variety of environmental insults. This adaptive response is particularly important for nongrowing cells, to which it confers a multiple, nonspecific, and preemptive stress resistance. Induction of the general stress response relies on the alternative transcription factor, SigB, whose activity is controlled by a partner switching mechanism that also involves the anti-sigma factor, RsbW, and the antagonist protein, RsbV. Recently, the SigB regulon has been shown to be continuously induced and functionally important in cells actively growing at low temperature. With the exception of this chill induction, all SigB-activating stimuli identified so far trigger a transient expression of the SigB regulon that depends on RsbV. Through a proteome analysis and Northern blot and gene fusion experiments, we now show that the SigB regulon is continuously induced in cells growing actively at 51°C, close to the upper growth limit of B. subtilis. This heat induction of SigB-dependent genes requires the environmental stress-responsive phosphatase RsbU, but not the metabolic stress-responsive phosphatase RsbP. RsbU dependence of SigB activation by heat is overcome in mutants that lack RsbV. In addition, loss of RsbV alone or in combination with RsbU triggers a hyperactivation of the general stress regulon exclusively at high temperatures detrimental for cell growth. These new facets of heat induction of the SigB regulon indicate that the current view of the complex genetic and biochemical regulation of SigB activity is still incomplete and that SigB perceives signals independent of the RsbV-mediated signal transduction pathways under heat stress conditions. PMID:15342585

Diagnosis of the three-phase induction motor using thermal imaging

NASA Astrophysics Data System (ADS)

Glowacz, Adam; Glowacz, Zygfryd

2017-03-01

Three-phase induction motors are used in the industry commonly for example woodworking machines, blowers, pumps, conveyors, elevators, compressors, mining industry, automotive industry, chemical industry and railway applications. Diagnosis of faults is essential for proper maintenance. Faults may damage a motor and damaged motors generate economic losses caused by breakdowns in production lines. In this paper the authors develop fault diagnostic techniques of the three-phase induction motor. The described techniques are based on the analysis of thermal images of three-phase induction motor. The authors analyse thermal images of 3 states of the three-phase induction motor: healthy three-phase induction motor, three-phase induction motor with 2 broken bars, three-phase induction motor with faulty ring of squirrel-cage. In this paper the authors develop an original method of the feature extraction of thermal images MoASoID (Method of Areas Selection of Image Differences). This method compares many training sets together and it selects the areas with the biggest changes for the recognition process. Feature vectors are obtained with the use of mentioned MoASoID and image histogram. Next 3 methods of classification are used: NN (the Nearest Neighbour classifier), K-means, BNN (the back-propagation neural network). The described fault diagnostic techniques are useful for protection of three-phase induction motor and other types of rotating electrical motors such as: DC motors, generators, synchronous motors.

Machine learning methods applied on dental fear and behavior management problems in children.

PubMed

Klingberg, G; Sillén, R; Norén, J G

1999-08-01

The etiologies of dental fear and dental behavior management problems in children were investigated in a database of information on 2,257 Swedish children 4-6 and 9-11 years old. The analyses were performed using computerized inductive techniques within the field of artificial intelligence. The database held information regarding dental fear levels and behavior management problems, which were defined as outcomes, i.e. dependent variables. The attributes, i.e. independent variables, included data on dental health and dental treatments, information about parental dental fear, general anxiety, socioeconomic variables, etc. The data contained both numerical and discrete variables. The analyses were performed using an inductive analysis program (XpertRule Analyser, Attar Software Ltd, Lancashire, UK) that presents the results in a hierarchic diagram called a knowledge tree. The importance of the different attributes is represented by their position in this diagram. The results show that inductive methods are well suited for analyzing multifactorial and complex relationships in large data sets, and are thus a useful complement to multivariate statistical techniques. The knowledge trees for the two outcomes, dental fear and behavior management problems, were very different from each other, suggesting that the two phenomena are not equivalent. Dental fear was found to be more related to non-dental variables, whereas dental behavior management problems seemed connected to dental variables.

Quantitative Comparison of Minimum Inductance and Minimum Power Algorithms for the Design of Shim Coils for Small Animal Imaging

PubMed Central

HUDSON, PARISA; HUDSON, STEPHEN D.; HANDLER, WILLIAM B.; SCHOLL, TIMOTHY J.; CHRONIK, BLAINE A.

2010-01-01

High-performance shim coils are required for high-field magnetic resonance imaging and spectroscopy. Complete sets of high-power and high-performance shim coils were designed using two different methods: the minimum inductance and the minimum power target field methods. A quantitative comparison of shim performance in terms of merit of inductance (ML) and merit of resistance (MR) was made for shim coils designed using the minimum inductance and the minimum power design algorithms. In each design case, the difference in ML and the difference in MR given by the two design methods was <15%. Comparison of wire patterns obtained using the two design algorithms show that minimum inductance designs tend to feature oscillations within the current density; while minimum power designs tend to feature less rapidly varying current densities and lower power dissipation. Overall, the differences in coil performance obtained by the two methods are relatively small. For the specific case of shim systems customized for small animal imaging, the reduced power dissipation obtained when using the minimum power method is judged to be more significant than the improvements in switching speed obtained from the minimum inductance method. PMID:20411157

Uncertain decision tree inductive inference

NASA Astrophysics Data System (ADS)

Zarban, L.; Jafari, S.; Fakhrahmad, S. M.

2011-10-01

Induction is the process of reasoning in which general rules are formulated based on limited observations of recurring phenomenal patterns. Decision tree learning is one of the most widely used and practical inductive methods, which represents the results in a tree scheme. Various decision tree algorithms have already been proposed such as CLS, ID3, Assistant C4.5, REPTree and Random Tree. These algorithms suffer from some major shortcomings. In this article, after discussing the main limitations of the existing methods, we introduce a new decision tree induction algorithm, which overcomes all the problems existing in its counterparts. The new method uses bit strings and maintains important information on them. This use of bit strings and logical operation on them causes high speed during the induction process. Therefore, it has several important features: it deals with inconsistencies in data, avoids overfitting and handles uncertainty. We also illustrate more advantages and the new features of the proposed method. The experimental results show the effectiveness of the method in comparison with other methods existing in the literature.

Hormonal induction of transfected genes depends on DNA topology.

PubMed Central

Piña, B; Haché, R J; Arnemann, J; Chalepakis, G; Slater, E P; Beato, M

1990-01-01

Plasmids containing the hormone regulatory element of mouse mammary tumor virus linked to the thymidine kinase promoter of herpes simplex virus and the reporter gene chloramphenicol acetyltransferase of Escherichia coli respond to glucocorticoids and progestins when transfected into appropriate cells. In the human mammary tumor cell line T47D, the response to progestins, but not to glucocorticoids, is highly dependent on the topology of the transfected DNA. Although negatively supercoiled plasmids respond optimally to the synthetic progestin R5020, their linearized counterparts exhibit markedly reduced progestin inducibility. This is not due to changes in the efficiency of DNA transfection, since the amount of DNA incorporated into the cell nucleus is not significantly dependent on the initial topology of the plasmids. In contrast, cotransfection experiments with glucocorticoid receptor cDNA in the same cell line show no significant influence of DNA topology on induction by dexamethasone. A similar result was obtained with fibroblasts that contain endogenous glucocorticoid receptors. When the distance between receptor-binding sites or between the binding sites and the promoter was increased, the dependence of progestin induction on DNA topology was more pronounced. In contrast to the original plasmid, these constructs also revealed a similar topological dependence for induction by glucocorticoids. The differential influence of DNA topology is not due to differences in the affinity of the two hormone receptors for DNA of various topologies, but probably reflects an influence of DNA topology on the interaction between different DNA-bound receptor molecules and between receptors and other transcription factors. Images PMID:2153920

Research on the method of establishing the total radiation meter calibration device

NASA Astrophysics Data System (ADS)

Gao, Jianqiang; Xia, Ming; Xia, Junwen; Zhang, Dong

2015-10-01

Pyranometer is an instrument used to measure the solar radiation, according to pyranometer differs as installation state, can be respectively measured total solar radiation, reflected radiation, or with the help of shading device for measuring scattering radiation. Pyranometer uses the principle of thermoelectric effect, inductive element adopts winding plating type multi junction thermopile, its surface is coated with black coating with high absorption rate. Hot junction in the induction surface, while the cold junction is located in the body, the cold and hot junction produce thermoelectric potential. In the linear range, the output signal is proportional to the solar irradiance. Traceability to national meteorological station, as the unit of the national legal metrology organizations, the responsibility is to transfer value of the sun and the earth radiation value about the national meteorological industry. Using the method of comparison, with indoor calibration of solar simulator, at the same location, standard pyranometer and measured pyranometer were alternately measured radiation irradiance, depending on the irradiation sensitivity standard pyranometer were calculated the radiation sensitivity of measured pyranometer. This paper is mainly about the design and calibration method of the pyranometer indoor device. The uncertainty of the calibration result is also evaluated.

The mutual inductance calculation between circular and quadrilateral coils at arbitrary attitudes using a rotation matrix for airborne transient electromagnetic systems

NASA Astrophysics Data System (ADS)

Ji, Yanju; Wang, Hongyuan; Lin, Jun; Guan, Shanshan; Feng, Xue; Li, Suyi

2014-12-01

Performance testing and calibration of airborne transient electromagnetic (ATEM) systems are conducted to obtain the electromagnetic response of ground loops. It is necessary to accurately calculate the mutual inductance between transmitting coils, receiving coils and ground loops to compute the electromagnetic responses. Therefore, based on Neumann's formula and the measured attitudes of the coils, this study deduces the formula for the mutual inductance calculation between circular and quadrilateral coils, circular and circular coils, and quadrilateral and quadrilateral coils using a rotation matrix, and then proposes a method to calculate the mutual inductance between two coils at arbitrary attitudes (roll, pitch, and yaw). Using coil attitude simulated data of an ATEM system, we calculate the mutual inductance of transmitting coils and ground loops at different attitudes, analyze the impact of coil attitudes on mutual inductance, and compare the computational accuracy and speed of the proposed method with those of other methods using the same data. The results show that the relative error of the calculation is smaller and that the speed-up is significant compared to other methods. Moreover, the proposed method is also applicable to the mutual inductance calculation of polygonal and circular coils at arbitrary attitudes and is highly expandable.

A "Large and Graceful Sinuosity": John Herschel's Graphical Method

NASA Astrophysics Data System (ADS)

Hankins, Thomas L.

2006-12-01

In 1833 John Herschel published a graphical method for determining the orbits of double stars. He argued that this method, which depended on human judgment rather than mathematical analysis, gave better results than computation, given the uncertainty in the data. Herschel found that astronomy and terrestrial physics were especially suitable for graphical treatment, and he expected that graphs would soon become important in all areas of science. He argued with William Whewell and James D. Forbes over the process of induction, over the application of probability, and over the moral content of science. Graphs entered into all these debates, but because they constituted a method, not a metaphysics, they were acceptable to most practicing scientists and became increasingly popular throughout the nineteenth century.

Induction Curing of Thiol-acrylate and Thiolene Composite Systems

PubMed Central

Ye, Sheng; Cramer, Neil B.; Stevens, Blake E.; Sani, Robert L.; Bowman, Christopher N.

2011-01-01

Induction curing is demonstrated as a novel type of in situ radiation curing that maintains most of the advantages of photocuring while eliminating the restriction of light accessibility. Induction curing is utilized to polymerize opaque composites comprised of thiol-acrylate and thiol-ene resins, nanoscale magnetic particles, and carbon nanotubes. Nanoscale magnetic particles are dispersed in the resin and upon exposure to the magnetic field, these particles lead to induction heating that rapidly initiates the polymerization. Heat transfer profiles and reaction kinetics of the samples are modeled during the reactions with varying induction heater power, species concentration, species type and sample thickness, and the model is compared with the experimental results. Thiol-ene polymerizations achieved full conversion between 1.5 minutes and 1 hour, depending on the field intensity and the composition, with the maximum reaction temperature decreasing from 146 – 87 °C when the induction heater power was decreased from 8 – 3 kW. The polymerization reactions of the thiol-acrylate system were demonstrated to achieve full conversion between 0.6 and 30 minutes with maximum temperatures from 139 to 86 °C. The experimental behavior was characterized and the temperature profile modeled for the thiol-acrylate composite comprised of sub100nm nickel particles and induction heater power in the range of 32 to 20 kW. A 9°C average deviation was observed between the modeling and experimental results for the maximum temperature rise. The model also was utilized to predict reaction temperatures and kinetics for systems with varying thermal initiator concentration, initiator half-life, monomer molecular weight and temperature gradients in samples with varying thickness, thereby demonstrating that induction curing represents a designable and tunable polymerization method. Finally, induction curing was utilized to cure thiol-acrylate systems containing carbon nanotubes where 1 wt% carbon nanotubes resulted in systems where the storage modulus increased from 17.6 ± 0.2 to 21.6 ± 0.1 MPa and an electrical conductivity that increased from <10−7 to 0.33 ± 0.5 S/m. PMID:21765552

Comparison of 2D and 3D neural induction methods for the generation of neural progenitor cells from human induced pluripotent stem cells.

PubMed

Chandrasekaran, Abinaya; Avci, Hasan X; Ochalek, Anna; Rösingh, Lone N; Molnár, Kinga; László, Lajos; Bellák, Tamás; Téglási, Annamária; Pesti, Krisztina; Mike, Arpad; Phanthong, Phetcharat; Bíró, Orsolya; Hall, Vanessa; Kitiyanant, Narisorn; Krause, Karl-Heinz; Kobolák, Julianna; Dinnyés, András

2017-12-01

Neural progenitor cells (NPCs) from human induced pluripotent stem cells (hiPSCs) are frequently induced using 3D culture methodologies however, it is unknown whether spheroid-based (3D) neural induction is actually superior to monolayer (2D) neural induction. Our aim was to compare the efficiency of 2D induction with 3D induction method in their ability to generate NPCs, and subsequently neurons and astrocytes. Neural differentiation was analysed at the protein level qualitatively by immunocytochemistry and quantitatively by flow cytometry for NPC (SOX1, PAX6, NESTIN), neuronal (MAP2, TUBB3), cortical layer (TBR1, CUX1) and glial markers (SOX9, GFAP, AQP4). Electron microscopy demonstrated that both methods resulted in morphologically similar neural rosettes. However, quantification of NPCs derived from 3D neural induction exhibited an increase in the number of PAX6/NESTIN double positive cells and the derived neurons exhibited longer neurites. In contrast, 2D neural induction resulted in more SOX1 positive cells. While 2D monolayer induction resulted in slightly less mature neurons, at an early stage of differentiation, the patch clamp analysis failed to reveal any significant differences between the electrophysiological properties between the two induction methods. In conclusion, 3D neural induction increases the yield of PAX6 + /NESTIN + cells and gives rise to neurons with longer neurites, which might be an advantage for the production of forebrain cortical neurons, highlighting the potential of 3D neural induction, independent of iPSCs' genetic background. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

The role of accessory cells in polyclonal T cell activation. I. Both induction of interleukin 2 production and of interleukin 2 responsiveness by concanavalin A are accessory cell dependent.

PubMed

Hünig, T; Loos, M; Schimpl, A

1983-01-01

Recent studies from other laboratories have shown that concanavalin A (Con A) acts at two separate steps in polyclonal T cell activation: interleukin 2 (IL2) production, and induction of responsiveness to IL2. Using a combination of techniques for the depletion of accessory cells from lymph node T cells, we have investigated which of these steps, if not both, is responsible for the known requirement for accessory cells in the Con A response. It was found that with increasing T cell purification, first the ability is lost to produce sufficient levels of endogenous IL2, whereas induction of IL2 responsiveness can still take place. Further removal of accessory cells however yields a population of resting T cells that cannot be induced by Con A to become IL2-reactive. It was concluded that both IL2 production and induction of reactivity to IL2 are accessory cell-dependent events.

Sex-related difference in the inductions by perfluoro-octanoic acid of peroxisomal beta-oxidation, microsomal 1-acylglycerophosphocholine acyltransferase and cytosolic long-chain acyl-CoA hydrolase in rat liver.

PubMed Central

Kawashima, Y; Uy-Yu, N; Kozuka, H

1989-01-01

Inductions by perfluoro-octanoic acid (PFOA) of hepatomegaly, peroxisomal beta-oxidation, microsomal 1-acylglycerophosphocholine acyltransferase and cytosolic long-chain acyl-CoA hydrolase were compared in liver between male and female rats. Marked inductions of these four parameters were seen concurrently in liver of male rats, whereas the inductions in liver of female rats were far less pronounced. The sex-related difference in the response of rat liver to PFOA was much more marked than that seen with p-chlorophenoxyisobutyric acid (clofibric acid) or 2,2'-(decamethylenedithio)diethanol (tiadenol). Hormonal manipulations revealed that this sex-related difference in the inductions is strongly dependent on sex hormones, namely that testosterone is necessary for the inductions, whereas oestradiol prevented the inductions by PFOA. PMID:2570571

Cytochemical and Cytofluorometric Evidence for Guard Cell Photosystems 1

PubMed Central

Vaughn, Kevin C.; Outlaw, William H.

1983-01-01

Evidence for photosynthetic linear electron transport in guard cells was obtained with two sensitive methods of high spacial resolution. Light-dependent diaminobenzidine oxidation (an indicator of PSI) and DCMU-sensitive, light-dependent thiocarbamyl nitroblue tetrazolium reduction (an indicator of PSII) were observed in guard cell plastids of Hordeum vulgare L. cv Himalaya using electron microscopic cytochemical procedures. DCMU-sensitive Chl a fluorescence induction (an indicator of PSII) was detected in individual guard cell pairs of Vicia faba L. cv Longpod using an ultramicrofluorometer. At least for these species, we conclude these results are proof for the presence of PSII in guard cell chloroplasts, which until now has been somewhat controversial. Images Fig. 2 Fig. 1 PMID:16662840

Nitric oxide donors for cervical ripening and induction of labour.

PubMed

Kelly, Anthony J; Munson, Christopher; Minden, Lucy

2011-06-15

Sometimes it is necessary to bring on labour artificially because of safety concerns for the mother or baby. This review is one of a series of reviews of methods of labour induction using a standardised protocol.Induction of labour occurs in approximately 20% of pregnancies in the UK. The ideal agent for induction of labour would induce cervical ripening without causing uterine contractions. Currently most commonly used cervical ripening or induction agents result in uterine activity or contractions, or both. Cervical ripening without uterine contractility could occur safely in an outpatient setting and it may be expected that this would result in greater maternal satisfaction and lower costs. To determine the effects of nitric oxide (NO) donors for third trimester cervical ripening or induction of labour, in comparison with placebo or no treatment or other treatments from a predefined hierarchy. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 December 2010) and the reference lists of trial reports and reviews. Clinical trials comparing NO donors for cervical ripening or labour induction to other methods listed above it on a predefined list of methods of labour induction. The trials include some form of random allocation to either group; and report one or more of the prestated outcomes. NO donors (isosorbide mononitrate, nitroglycerin and sodium nitroprusside) are compared to other methods listed above it on a predefined list of methods of labour induction. This review is part of a series of reviews focusing on methods of induction of labour. Three review authors independently assessed trials for inclusion, assessed risk of bias and extracted data. We considered 19 trials; we included 10 (including a total of 1889 women) trials, excluded eight trials and one trial report is awaiting classification. Included studies compared NO donors to placebo, vaginal prostaglandin E2, intracervical PGE2 and vaginal misoprostol. All included studies were of a generally high standard with a low risk of bias.There are very limited data available to compare nitric oxide donors to any other induction agent. There is no evidence of any difference between any of the prespecified outcomes when comparing NO donors to other induction agents, with the exception of an increase in maternal side effects. NO donors do not appear currently to be a useful tool in the process of induction of labour. More studies are required to examine how NO donors may work alongside established induction of labour protocols, especially those based in outpatient settings.

Periodic acid‑Schiff staining method for function detection of liver cells is affected by 2% horse serum in induction medium.

PubMed

Hui, Hui; Ma, Wenjun; Cui, Jiejie; Gong, Mengjia; Wang, Yi; Zhang, Yuanyuan; He, Tongchuan; Bi, Yang; He, Yun

2017-12-01

Developing a thorough understanding of experimental methods of hepatic differentiation in hepatic progenitor cells (HPCs) should expand the knowledge of hepatocyte induction in vitro and may help to develop cell transplantation therapies for the clinical usage of HPCs in liver diseases. A previous induction method effectively induced differentiation and metabolic abilities in HPCs. Periodic acid‑Schiff (PAS) staining is used to identify glycogen synthesis and hepatocyte function; however, this method failed to detect induced hepatocytes. The present study aimed to investigate the possible factors affecting the previous confusing results of PAS staining. Removal of single induction factors, including dexamethasone, hepatic growth factor and fibroblast growth factor 4 from the induction media did not restore PAS staining, whereas replacement of 2% horse serum (HS) with 10% fetal bovine serum (FBS) significantly increased the number of PAS positive cells. Following 12 days of basal induction, replacing the induction medium with media containing 10% FBS for 12‑72 h significantly improved PAS staining, but did not influence indocyanine green uptake. Furthermore, incubation in induction medium with 10% FBS following 12 days of normal induction did not affect the expression of hepatic markers and mature function of HPCs. Therefore, the present study suggested that 2% HS in the induction medium did not affect the hepatic function of induced cells, but did affect glycogen storage, whereas replacement of medium with 10% FBS in advance of PAS staining may restore the failure of PAS staining in low serum concentrations of induced hepatocytes.

Numerical calculation of primary slot leakage inductance of a Single-sided HTS linear induction motor used for linear metro

NASA Astrophysics Data System (ADS)

Li, Dong; Wen, Yinghong; Li, Weili; Fang, Jin; Cao, Junci; Zhang, Xiaochen; Lv, Gang

2017-03-01

In the paper, the numerical method calculating asymmetric primary slot leakage inductances of Single-sided High-Temperature Superconducting (HTS) Linear Induction Motor (HTS LIM) is presented. The mathematical and geometric models of three-dimensional nonlinear transient electromagnetic field are established and the boundary conditions are also given. The established model is solved by time-stepping Finite Element Method (FEM). Then, the three-phase asymmetric primary slot leakage inductances under different operation conditions are calculated by using the obtained electromagnetic field distribution. The influences of the special effects such as longitudinal end effects, transversal edge effects, etc. on the primary slot leakage inductance are investigated. The presented numerical method is validated by experiments carried out on a 3.5 kW prototype with copper wires which has the same structures with the HTS LIM.

Two Undergraduate Process Modeling Courses Taught Using Inductive Learning Methods

ERIC Educational Resources Information Center

Soroush, Masoud; Weinberger, Charles B.

2010-01-01

This manuscript presents a successful application of inductive learning in process modeling. It describes two process modeling courses that use inductive learning methods such as inquiry learning and problem-based learning, among others. The courses include a novel collection of multi-disciplinary complementary process modeling examples. They were…

Recruiting Unmotivated Smokers into a Smoking Induction Trial

ERIC Educational Resources Information Center

Harris, Kari Jo; Bradley-Ewing, Andrea; Goggin, Kathy; Richter, Kimber P.; Patten, Christi; Williams, Karen; Lee, Hyoung S.; Staggs, Vincent S.; Catley, Delwyn

2016-01-01

Little is known about effective methods to recruit unmotivated smokers into cessation induction trials, the reasons unmotivated smokers agree to participate, and the impact of those reasons on study outcomes. A mixed-method approach was used to examine recruitment data from a randomized controlled cessation induction trial that enrolled 255 adult…

Time-Resolved O3 Chemical Chain Reaction Kinetics Via High-Resolution IR Laser Absorption Methods

NASA Technical Reports Server (NTRS)

Kulcke, Axel; Blackmon, Brad; Chapman, William B.; Kim, In Koo; Nesbitt, David J.

1998-01-01

Excimer laser photolysis in combination with time-resolved IR laser absorption detection of OH radicals has been used to study O3/OH(v = 0)/HO2 chain reaction kinetics at 298 K, (i.e.,(k(sub 1) is OH + 03 yields H02 + 02 and (k(sub 2) is H02 + 03 yields OH + 202). From time-resolved detection of OH radicals with high-resolution near IR laser absorption methods, the chain induction kinetics have been measured at up to an order of magnitude higher ozone concentrations ([03] less than or equal to 10(exp 17) molecules/cu cm) than accessible in previous studies. This greater dynamic range permits the full evolution of the chain induction, propagation, and termination process to be temporally isolated and measured in real time. An exact solution for time-dependent OH evolution under pseudo- first-order chain reaction conditions is presented, which correctly predicts new kinetic signatures not included in previous OH + 03 kinetic analyses. Specifically, the solutions predict an initial exponential loss (chain "induction") of the OH radical to a steady-state level ([OH](sub ss)), with this fast initial decay determined by the sum of both chain rate constants, k(sub ind) = k(sub 1) + k(sub 2). By monitoring the chain induction feature, this sum of the rate constants is determined to be k(sub ind) = 8.4(8) x 10(exp -14) cu cm/molecule/s for room temperature reagents. This is significantly higher than the values currently recommended for use in atmospheric models, but in excellent agreement with previous results from Ravishankara et al.

Anomalous satellite inductive peaks in alternating current response of defective carbon nanotubes

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

Hirai, Daisuke; Watanabe, Satoshi; Yamamoto, Takahiro

2014-05-07

AC response of defective metallic carbon nanotubes is investigated from first principles. We found that capacitive peaks appear at electron scattering states. Moreover, we show that satellite inductive peaks are seen adjacent to a main capacitive peak, which is in contrast to the conductance spectra having no satellite features. The appearance of satellite inductive peaks seems to depend on the scattering states. Our analysis with a simple resonant scattering model reveals that the origin of the satellite inductive peaks can be understood by just one parameter, i.e., the lifetime of electrons at a defect state.

Accuracy of iron loss estimation in induction motors by using different iron loss models

NASA Astrophysics Data System (ADS)

Štumberger, B.; Hamler, A.; Goričan, V.; Jesenik, M.; Trlep, M.

2004-05-01

The paper presents iron loss estimation in a three-phase induction motor by using different iron loss models for the posterior iron loss calculation. The iron losses were determined by using modeled properties of used electrical steel and calculated distribution of magnetic induction B(t) in all parts of the motor by using 2D finite element software for a complete cycle of field variation. The comparison between estimated and measured core losses for a 4kW induction motor at no-load in dependency on supply voltage is given.

The Hog1 Mitogen-Activated Protein Kinase Mediates a Hypoxic Response in Saccharomyces cerevisiae

PubMed Central

Hickman, Mark J.; Spatt, Dan; Winston, Fred

2011-01-01

We have studied hypoxic induction of transcription by studying the seripauperin (PAU) genes of Saccharomyces cerevisiae. Previous studies showed that PAU induction requires the depletion of heme and is dependent upon the transcription factor Upc2. We have now identified additional factors required for PAU induction during hypoxia, including Hog1, a mitogen-activated protein kinase (MAPK) whose signaling pathway originates at the membrane. Our results have led to a model in which heme and ergosterol depletion alters membrane fluidity, thereby activating Hog1 for hypoxic induction. Hypoxic activation of Hog1 is distinct from its previously characterized response to osmotic stress, as the two conditions cause different transcriptional consequences. Furthermore, Hog1-dependent hypoxic activation is independent of the S. cerevisiae general stress response. In addition to Hog1, specific components of the SAGA coactivator complex, including Spt20 and Sgf73, are also required for PAU induction. Interestingly, the mammalian ortholog of Spt20, p38IP, has been previously shown to interact with the mammalian ortholog of Hog1, p38. Taken together, our results have uncovered a previously unknown hypoxic-response pathway that may be conserved throughout eukaryotes. PMID:21467572

Ionotropic NMDA receptor signaling is required for the induction of long-term depression in the mouse hippocampal CA1 region.

PubMed

Babiec, Walter E; Guglietta, Ryan; Jami, Shekib A; Morishita, Wade; Malenka, Robert C; O'Dell, Thomas J

2014-04-09

Previous studies have provided strong support for the notion that NMDAR-mediated increases in postsynaptic Ca(2+) have a crucial role in the induction of long-term depression (LTD). This view has recently been challenged, however, by findings suggesting that LTD induction is instead attributable to an ion channel-independent, metabotropic form of NMDAR signaling. Thus, to explore the role of ionotropic versus metabotropic NMDAR signaling in LTD, we examined the effects of varying extracellular Ca(2+) levels or blocking NMDAR channel ion fluxes with MK-801 on LTD and NMDAR signaling in the mouse hippocampal CA1 region. We find that the induction of LTD in the adult hippocampus is highly sensitive to extracellular Ca(2+) levels and that MK-801 blocks NMDAR-dependent LTD in the hippocampus of both adult and immature mice. Moreover, MK-801 inhibits NMDAR-mediated activation of p38-MAPK and dephosphorylation of AMPAR GluA1 subunits at sites implicated in LTD. Thus, our results indicate that the induction of LTD in the hippocampal CA1 region is dependent on ionotropic, rather than metabotropic, NMDAR signaling.

Use of non-medical methods of labor induction and pain management among U.S. women

PubMed Central

Kozhimanil, Katy Backes; Johnson, Pamela Jo; Attanasio, Laura B.; Gjerdingen, Dwenda K.; McGovern, Patricia M.

2013-01-01

Background There is limited documentation of non-medical methods of labor induction and pain management during childbirth in the U.S. We estimated the prevalence of non-medical interventions for induction and pain management and examined the association between medical and non-medical care during labor. Methods We used a nationally-representative survey of U.S. women who gave birth in 2005 (N=1,382) to examine use of non-medical methods of labor induction and pain management. Using logistic regression, we calculated odds of non-medical and medical interventions to induce labor or mitigate pain, and the odds of medical induction and obstetric analgesia by whether non-medical methods were used. Results Nearly 30% of women used non-medical methods to start labor, and over 70% of women used non-medical pain management. Doula support was the strongest predictor of non-medical methods of labor induction (Adjusted Odds Ratio (AOR) = 3.0) and labor pain management (AOR = 5.7). Use of non-medical pain management was significantly associated with decreased odds of medical pain management (OR = 0.65); this relationship was attenuated with covariate adjustment. Conclusions Non-medical methods to induce labor and manage pain during childbirth are commonly used by U.S. women. Future research should examine effectiveness of these strategies and their influence on medical services use. PMID:24344703

R package PRIMsrc: Bump Hunting by Patient Rule Induction Method for Survival, Regression and Classification

PubMed Central

Dazard, Jean-Eudes; Choe, Michael; LeBlanc, Michael; Rao, J. Sunil

2015-01-01

PRIMsrc is a novel implementation of a non-parametric bump hunting procedure, based on the Patient Rule Induction Method (PRIM), offering a unified treatment of outcome variables, including censored time-to-event (Survival), continuous (Regression) and discrete (Classification) responses. To fit the model, it uses a recursive peeling procedure with specific peeling criteria and stopping rules depending on the response. To validate the model, it provides an objective function based on prediction-error or other specific statistic, as well as two alternative cross-validation techniques, adapted to the task of decision-rule making and estimation in the three types of settings. PRIMsrc comes as an open source R package, including at this point: (i) a main function for fitting a Survival Bump Hunting model with various options allowing cross-validated model selection to control model size (#covariates) and model complexity (#peeling steps) and generation of cross-validated end-point estimates; (ii) parallel computing; (iii) various S3-generic and specific plotting functions for data visualization, diagnostic, prediction, summary and display of results. It is available on CRAN and GitHub. PMID:26798326

Robust Induction of DARPP32-Expressing GABAergic Striatal Neurons from Human Pluripotent Stem Cells.

PubMed

Fjodorova, Marija; Li, Meng

2018-01-01

Efficient generation of disease relevant neuronal subtypes from human pluripotent stem cells (PSCs) is fundamental for realizing their promise in disease modeling, pharmaceutical drug screening and cell therapy. Here we describe a step-by-step protocol for directing the differentiation of human embryonic and induced PSCs (hESCs and hiPSCs, respectively) toward medium spiny neurons, the type of cells that are preferentially lost in Huntington's disease patients. This method is based on a novel concept of Activin A-dependent induction of the lateral ganglionic/striatal fate using a simple monolayer culture paradigm under chemically defined conditions. Transplantable medium spiny neuron progenitors amenable for cryopreservation are produced in less than 20 days, which differentiate and mature into a high yield of dopamine- and cAMP-regulated phosphoprotein, Mr 32 kDa (DARPP32) expressing gamma-aminobutyric acid (GABA)-ergic neurons in vitro and in the adult rat brain after transplantation. This method has been validated in multiple hESC and hiPSC lines, and is independent of the regime for PSC maintenance.

Alfvén simple waves

NASA Astrophysics Data System (ADS)

Webb, G. M.; Zank, G. P.; Burrows, R. H.; Ratkiewicz, R. E.

2011-02-01

Multi-dimensional Alfvén simple waves in magnetohydrodynamics (MHD) are investigated using Boillat's formalism. For simple wave solutions, all physical variables (the gas density, pressure, fluid velocity, entropy, and magnetic field induction in the MHD case) depend on a single phase function ϕ, which is a function of the space and time variables. The simple wave ansatz requires that the wave normal and the normal speed of the wave front depend only on the phase function ϕ. This leads to an implicit equation for the phase function and a generalization of the concept of a plane wave. We obtain examples of Alfvén simple waves, based on the right eigenvector solutions for the Alfvén mode. The Alfvén mode solutions have six integrals, namely that the entropy, density, magnetic pressure, and the group velocity (the sum of the Alfvén and fluid velocity) are constant throughout the wave. The eigenequations require that the rate of change of the magnetic induction B with ϕ throughout the wave is perpendicular to both the wave normal n and B. Methods to construct simple wave solutions based on specifying either a solution ansatz for n(ϕ) or B(ϕ) are developed.

Alfven Simple Waves

NASA Astrophysics Data System (ADS)

Webb, G. M.; Zank, G. P.; Burrows, R.

2009-12-01

Multi-dimensional Alfvén simple waves in magnetohydrodynamics (MHD) are investigated using Boillat's formalism. For simple wave solutions, all physical variables (the gas density, pressure, fluid velocity, entropy, and magnetic field induction in the MHD case) depend on a single phase function ǎrphi which is a function of the space and time variables. The simple wave ansatz requires that the wave normal and the normal speed of the wave front depend only on the phase function ǎrphi. This leads to an implicit equation for the phase function, and a generalisation of the concept of a plane wave. We obtain examples of Alfvén simple waves, based on the right eigenvector solutions for the Alfvén mode. The Alfvén mode solutions have six integrals, namely that the entropy, density, magnetic pressure and the group velocity (the sum of the Alfvén and fluid velocity) are constant throughout the wave. The eigen-equations require that the rate of change of the magnetic induction B with ǎrphi throughout the wave is perpendicular to both the wave normal n and B. Methods to construct simple wave solutions based on specifying either a solution ansatz for n(ǎrphi) or B(ǎrphi) are developed.

Can we estimate plasma density in ICP driver through electrical parameters in RF circuit?

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

Bandyopadhyay, M., E-mail: mainak@iter-india.org; Sudhir, Dass, E-mail: dass.sudhir@iter-india.org; Chakraborty, A., E-mail: arunkc@iter-india.org

2015-04-08

To avoid regular maintenance, invasive plasma diagnostics with probes are not included in the inductively coupled plasma (ICP) based ITER Neutral Beam (NB) source design. Even non-invasive probes like optical emission spectroscopic diagnostics are also not included in the present ITER NB design due to overall system design and interface issues. As a result, negative ion beam current through the extraction system in the ITER NB negative ion source is the only measurement which indicates plasma condition inside the ion source. However, beam current not only depends on the plasma condition near the extraction region but also on the perveancemore » condition of the ion extractor system and negative ion stripping. Nevertheless, inductively coupled plasma production region (RF driver region) is placed at distance (∼ 30cm) from the extraction region. Due to that, some uncertainties are expected to be involved if one tries to link beam current with plasma properties inside the RF driver. Plasma characterization in source RF driver region is utmost necessary to maintain the optimum condition for source operation. In this paper, a method of plasma density estimation is described, based on density dependent plasma load calculation.« less

Increased sensitivity to apoptosis induced by methotrexate is mediated by Jun N-terminal kinase

PubMed Central

Spurlock, Charles F.; Aune, Zachary T.; Tossberg, John T.; Collins, Patrick L.; Aune, Jessica P.; Huston, Joseph W.; Crooke, Philip S.; Olsen, Nancy J.; Aune, Thomas M.

2011-01-01

Objective Low-dose methotrexate [MTX] is an effective therapy for rheumatoid arthritis yet its mechanism of action is incompletely understood. Here, we explored induction of apoptosis by MTX. Methods We employed flow cytometry to assess changes in levels of intracellular proteins, reactive oxygen species [ROS], and apoptosis.Quantitative polymerase chain reaction was usedtoassess changes in transcript levels of select target genes in response to MTX. Results MTX does not directly induce apoptosis but rather ‘primes’ cells for markedly increased sensitivity to apoptosis via either mitochondrial or death receptor pathways by a Jun N-terminal kinase [JNK]-dependent mechanism. Increased sensitivity to apoptosis is mediated, at least in part, by MTX-dependent production of reactive oxygen species, JNK activation and JNK-dependent induction of genes whose protein products promote apoptosis. Supplementation with tetrahydrobiopterin blocks these methotrexate-induced effects. Subjects with rheumatoid arthritis on low-dose MTX therapy express elevated levels of the JNK-target gene, JUN. Conclusions Our results support a model whereby methotrexate inhibits reduction of dihydrobiopterin to tetrahydrobiopterin resulting in increased production of ROS, increased JNK activity and increased sensitivity to apoptosis. The finding of increased JUN levels in subjects with RA taking low-dose MTX supports the notion that this pathway is activated by MTX, in vivo, and may contribute to efficacy of MTX in inflammatory disease. PMID:21618198

Identification of heparin-binding EGF-like growth factor as a target in intercellular regulation of epidermal basal cell growth by suprabasal retinoic acid receptors.

PubMed Central

Xiao, J H; Feng, X; Di, W; Peng, Z H; Li, L A; Chambon, P; Voorhees, J J

1999-01-01

The role of retinoic acid receptors (RARs) in intercellular regulation of cell growth was assessed by targeting a dominant-negative RARalpha mutant (dnRARalpha) to differentiated suprabasal cells of mouse epidermis. dnRARalpha lacks transcriptional activation but not DNA-binding and receptor dimerization functions. Analysis of transgenic mice revealed that dnRARalpha dose-dependently impaired induction of basal cell proliferation and epidermal hyperplasia by all-trans RA (tRA). dnRARalpha formed heterodimers with endogenous retinoid X receptor-alpha (RXRalpha) over RA response elements in competition with remaining endogenous RARgamma-RXRalpha heterodimers, and dose-dependently impaired retinoid-dependent gene transcription. To identify genes regulated by retinoid receptors and involved in cell growth control, we analyzed the retinoid effects on expression of the epidermal growth factor (EGF) receptor, EGF, transforming growth factor-alpha, heparin-binding EGF-like growth factor (HB-EGF) and amphiregulin genes. In normal epidermis, tRA rapidly and selectively induced expression of HB-EGF but not the others. This induction occurred exclusively in suprabasal cells. In transgenic epidermis, dnRARalpha dose-dependently inhibited tRA induction of suprabasal HB-EGF and subsequent basal cell hyperproliferation. Together, our observations suggest that retinoid receptor heterodimers located in differentiated suprabasal cells mediate retinoid induction of HB-EGF, which in turn stimulates basal cell growth via intercellular signaling. These events may underlie retinoid action in epidermal regeneration during wound healing. PMID:10075925

Top-level dynamics and the regulated gene response of feed-forward loop transcriptional motifs.

PubMed

Mayo, Michael; Abdelzaher, Ahmed; Perkins, Edward J; Ghosh, Preetam

2014-09-01

Feed-forward loops are hierarchical three-node transcriptional subnetworks, wherein a top-level protein regulates the activity of a target gene via two paths: a direct-regulatory path, and an indirect route, whereby the top-level proteins act implicitly through an intermediate transcription factor. Using a transcriptional network of the model bacterium Escherichia coli, we confirmed that nearly all types of feed-forward loop were significantly overrepresented in the bacterial network. We then used mathematical modeling to study their dynamics by manipulating the rise times of the top-level protein concentration, termed the induction time, through alteration of the protein destruction rates. Rise times of the regulated proteins exhibited two qualitatively different regimes, depending on whether top-level inductions were "fast" or "slow." In the fast regime, rise times were nearly independent of rapid top-level inductions, indicative of biological robustness, and occurred when RNA production rate-limits the protein yield. Alternatively, the protein rise times were dependent upon slower top-level inductions, greater than approximately one bacterial cell cycle. An equation is given for this crossover, which depends upon three parameters of the direct-regulatory path: transcriptional cooperation at the DNA-binding site, a protein-DNA dissociation constant, and the relative magnitude of the top-level protien concentration.

Regulation of rat heme oxygenase-1 expression by interleukin-6 via the Jak/STAT pathway in hepatocytes.

PubMed

Tron, Kyrylo; Samoylenko, Anatoly; Musikowski, Gernot; Kobe, Fritz; Immenschuh, Stephan; Schaper, Fred; Ramadori, Giuliano; Kietzmann, Thomas

2006-07-01

Heme oxygenase-1 (HO-1) can be induced by various stimuli, one of which is interleukin-6 (IL-6). Therefore, the aim of this study was to elucidate the molecular mechanisms responsible for IL-6-dependent HO-1 induction in the liver. The IL-6-dependent HO-1 regulation in rat primary hepatocytes and HepG2 hepatoma cells was studied by Northern and Western blot analyses, HO-1 promoter reporter gene assays and EMSA. The HO-1 expression was transcriptionally induced by IL-6 in a time- and dose-dependent manner. Activation of signal transducers and activators of transcription (STAT) factors by the IL-6 receptor was crucial for HO-1 induction. By contrast, negative regulation of HO-1 expression appeared to be mediated through the SH2-domain-containing tyrosine phosphatase-2 (SHP2)/ suppressors of cytokine signaling-3 (SOCS3) binding site within the gp130 IL-6 receptor subunit. Among the three putative STAT binding elements (SBE) in the HO-1 promoter, only the distal one was functional and when deleted, the remaining Luc induction was completely obliterated by the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. The HO-1 SBE3 mediates HO-1 gene induction by IL-6 mainly via activation of the Jak/STAT pathway.

Dynamic regulation of VEGF-inducible genes by an ERK/ERG/p300 transcriptional network.

PubMed

Fish, Jason E; Cantu Gutierrez, Manuel; Dang, Lan T; Khyzha, Nadiya; Chen, Zhiqi; Veitch, Shawn; Cheng, Henry S; Khor, Melvin; Antounians, Lina; Njock, Makon-Sébastien; Boudreau, Emilie; Herman, Alexander M; Rhyner, Alexander M; Ruiz, Oscar E; Eisenhoffer, George T; Medina-Rivera, Alejandra; Wilson, Michael D; Wythe, Joshua D

2017-07-01

The transcriptional pathways activated downstream of vascular endothelial growth factor (VEGF) signaling during angiogenesis remain incompletely characterized. By assessing the signals responsible for induction of the Notch ligand delta-like 4 (DLL4) in endothelial cells, we find that activation of the MAPK/ERK pathway mirrors the rapid and dynamic induction of DLL4 transcription and that this pathway is required for DLL4 expression. Furthermore, VEGF/ERK signaling induces phosphorylation and activation of the ETS transcription factor ERG, a prerequisite for DLL4 induction. Transcription of DLL4 coincides with dynamic ERG-dependent recruitment of the transcriptional co-activator p300. Genome-wide gene expression profiling identified a network of VEGF-responsive and ERG-dependent genes, and ERG chromatin immunoprecipitation (ChIP)-seq revealed the presence of conserved ERG-bound putative enhancer elements near these target genes. Functional experiments performed in vitro and in vivo confirm that this network of genes requires ERK, ERG and p300 activity. Finally, genome-editing and transgenic approaches demonstrate that a highly conserved ERG-bound enhancer located upstream of HLX (which encodes a transcription factor implicated in sprouting angiogenesis) is required for its VEGF-mediated induction. Collectively, these findings elucidate a novel transcriptional pathway contributing to VEGF-dependent angiogenesis. © 2017. Published by The Company of Biologists Ltd.

Method of processing materials using an inductively coupled plasma

DOEpatents

Hull, Donald E.; Bieniewski, Thomas M.

1990-01-01

A method for making fine power using an inductively coupled plasma. The method provides a gas-free environment, since the plasma is formed without using a gas. The starting material used in the method is in solid form.

Why learning and development can lead to poorer recognition memory.

PubMed

Hayes, Brett K; Heit, Evan

2004-08-01

Current models of inductive reasoning in children and adults assume a central role for categorical knowledge. A recent paper by Sloutsky and Fisher challenges this assumption, showing that children are more likely than adults to rely on perceptual similarity as a basis for induction, and introduces a more direct method for examining the representations activated during induction. This method has the potential to constrain models of induction in novel ways, although there are still important challenges.

An Inductive Logic Programming Approach to Validate Hexose Binding Biochemical Knowledge.

PubMed

Nassif, Houssam; Al-Ali, Hassan; Khuri, Sawsan; Keirouz, Walid; Page, David

2010-01-01

Hexoses are simple sugars that play a key role in many cellular pathways, and in the regulation of development and disease mechanisms. Current protein-sugar computational models are based, at least partially, on prior biochemical findings and knowledge. They incorporate different parts of these findings in predictive black-box models. We investigate the empirical support for biochemical findings by comparing Inductive Logic Programming (ILP) induced rules to actual biochemical results. We mine the Protein Data Bank for a representative data set of hexose binding sites, non-hexose binding sites and surface grooves. We build an ILP model of hexose-binding sites and evaluate our results against several baseline machine learning classifiers. Our method achieves an accuracy similar to that of other black-box classifiers while providing insight into the discriminating process. In addition, it confirms wet-lab findings and reveals a previously unreported Trp-Glu amino acids dependency.

Induction patterns of structural mutations in barley leaf meristem upon the combined action of ionizing radiation and heavy metals

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

Geras`kin, S.A.; Dikarev, V.G.; Udalova, A.A.

1995-07-01

Environmental protection requires the development of principles, universal methods, and quantitative criteria for estimating the ecological risk of the combined effects of various factors on natural ecosystems. The combined action of these factors may induce complex multidirectional processes, e.g., the induction and inhibition of separation systems that result in a broad spectrum of cell responses (from antagonism to synergism), depending on the relative involvement of the factors. This was confirmed by numerous examples of nonlinear responses of biological systems to alterations in the order and level of damaging agents, as well as in the duration of their action. For thismore » reason, the response of a biological system to the combined action of various damaging factors cannot be predicted from the data on the separate action of factors. 7 refs., 3 figs., 2 tabs.« less

In vitro antigen-specific induction of IL-22 in human subjects that resolved HCV infection

PubMed Central

Cusick, Matthew F; Libbey, Jane E; Fujinami, Robert S; Eckels, David D

2012-01-01

Aims To determine if in vitro production of IL-22 and IL-17 correlated with resolution of HCV infection. Materials & methods Human peripheral blood cells isolated from a well-defined cohort of resolved and chronic HCV-infected subjects were used to measure HCV-, influenza- and mitogen-activated T-cell proliferation. In addition, IL-22 and IL-17 production was measured via ELISAs and flow cytometry. Results Resolved HCV subjects had a significantly higher T-cell proliferative response to recombinant NS3 protein compared with chronic HCV subjects. Resolved subjects had a dose-dependent IL-22 response to recombinant NS3 compared with chronic HCV subjects. Conclusion IL-22 production is associated with antigen-specific induction of CD4 + T cells in individuals that resolved HCV infection, suggesting a potential role for IL-22 in HCV clearance. PMID:23185211

Hyperthermia studies using inductive and ultrasound methods on E. coli bacteria and mouse glioma cells

NASA Astrophysics Data System (ADS)

Cabral-Prieto, A.; López-Callejas, R.; Rodríguez-Méndez, B. G.; Santos-Cuevas, C. L.; Celis-Almazán, J.; Olea-Mejía, O.; Gómez-Morales, J. L.; Peña-Eguiluz, R.; Valencia-Alvarado, R.; Mercado-Cabrera, A.; Muñoz-Castro, A. E.; García-Santibañez, F.

2017-11-01

The survival of Escherichia coli bacteria and mouse glioma cells were studied under different temperatures using direct heating in water, ultrasound, and magnetic fluid hyperthermia. The survival of these microorganisms depended on whether the heating mode was continuous or discontinuous, surviving more in the former than in the discontinuous heating mode. Whereas Escherichia coli bacteria did not survive at temperatures ≥50∘C, the mouse glioma cells did not survive at temperatures ≥48∘C. The survival of both these microorganisms was independent of the presence or absence of the magnetic nanoparticles of magnetite, suggesting that these, having mean particle sizes of 9.5, 8.5 and 5, did not show any apparent cytotoxicity effect. Present results also showed that the inductive heating system which used a radiofrequency of 13.56 MHz, providing a maximum magnetic field strength of 160 A/m, the electric rather than magnetic heating predominated.

Pb and Sr isotope measurements by inductively coupled plasma mass spectrometer: efficient time management for precision improvement

NASA Astrophysics Data System (ADS)

Monna, F.; Loizeau, J.-L.; Thomas, B. A.; Guéguen, C.; Favarger, P.-Y.

1998-08-01

One of the factors limiting the precision of inductively coupled plasma mass spectrometry is the counting statistics, which depend upon acquisition time and ion fluxes. In the present study, the precision of the isotopic measurements of Pb and Sr is examined. The time of measurement is optimally shared for each isotope, using a mathematical simulation, to provide the lowest theoretical analytical error. Different algorithms of mass bias correction are also taken into account and evaluated in term of improvement of overall precision. Several experiments allow a comparison of real conditions with theory. The present method significantly improves the precision, regardless of the instrument used. However, this benefit is more important for equipment which originally yields a precision close to that predicted by counting statistics. Additionally, the procedure is flexible enough to be easily adapted to other problems, such as isotopic dilution.

The Relationship Between Perceptual Egocentrism and Field Dependence in Early Childhood

ERIC Educational Resources Information Center

Bowd, Alan D.

1975-01-01

Kindergarten children were administered tests of inductive reasoning and field dependence and a series of perceptual egocentrism tasks. Results confirm a positive relation between field dependence and perceptual egocentrism; they also question the validity of the field-dependence construct in early childhood. (GO)

Issues on Reproducibility/Reliability of Magnetic NDE Methods

NASA Technical Reports Server (NTRS)

Namkung, M.; Fulton, J. P.; Wincheski, B.; Nath, S.

1994-01-01

One of the critical elements related to the practicality of any NDE technique is its reproducibility under nominally the same inspection conditions. The results of certain test methodologies, however, are not always repeatable and understanding the origin of the irreproducibility is often as critical as obtaining reproducible results. One example is the characterization of residual stress in structural ferromagnets using the magnetoacoustic (MAC) method. Although it has not been widely publicized, the test results of this method are known to be time-dependent. Two distinct types of time dependencies have been observed during testing. The first type has a clearly definable relaxation time, while no such trend has been observed for the second. The purpose of the present study is to systematically investigate the time dependence of the second type, to find out the range and, if possible, the origin of the variation in the test results. For this, MAC curves were obtained under various stress levels and the tests were repeated over time. Particular attention was given to whether noise in the measuring device or a change in the laboratory environment could have been a contributing factor. The steel samples used for the study were cut from C- and U-class railroad wheels. The MAC behavior of these samples was reported previously. Each steel sample was first machined to be a cylindrical rod of 3.175 cm (1.25 in) in diameter and 26.67 cm (10.5 in) in length. The center portion of the samples were further machined to form a pair of flat and parallel surfaces for the launch and reflection of the ultrasonic pulses. Data acquisition involved two major elements; magnetic and acoustic measurements. Throughout the experiment the net magnetic induction, B, was measured by integrating the induction pickup coil output using an integrating fluxmeter. The acoustic measurements employed the phase-locked technique which will be described in the following.

Beginning Secondary Science Teacher Induction: A Two-Year Mixed Methods Study

ERIC Educational Resources Information Center

Luft, Julie A.; Firestone, Jonah B.; Wong, Sissy S.; Ortega, Ira; Adams, Krista; Bang, EunJin

2011-01-01

Those who study secondary science teachers are often concerned with preservice or in-service teacher development. Science teacher educators have acknowledged that this focus is limited, as the induction years of beginning teachers are an important component of teacher development. This mixed methods study focuses on the induction years of…

Age-Dependent Glutamate Induction of Synaptic Plasticity in Cultured Hippocampal Neurons

ERIC Educational Resources Information Center

Ivenshitz, Miriam; Segal, Menahem; Sapoznik, Stav

2006-01-01

A common denominator for the induction of morphological and functional plasticity in cultured hippocampal neurons involves the activation of excitatory synapses. We now demonstrate massive morphological plasticity in mature cultured hippocampal neurons caused by a brief exposure to glutamate. This plasticity involves a slow, 70%-80% increase in…

Demonstration of Lenz's Law with an Induction Motor

ERIC Educational Resources Information Center

Kraftmakher, Yaakov

2005-01-01

The interaction of a conductor with a time-dependent magnetic field is an important topic of electromagnetic theory. A computerized classroom demonstration shows how the eddy currents induced in the rotor of an induction motor cause its rotation or braking. Both phenomena are directly related to Lenz's law.

Transfer Student Induction Model: Providing a Path to Connection

ERIC Educational Resources Information Center

Hubbuch, Chris; Stucker, Keelie

2015-01-01

Schools implementing positive behavioral interventions and supports work to establish and maintain fidelity of school-wide systems and practices. Depending on the mobility rate of the student population, initial efforts may not be enough to adequately support and personalize the induction experience for highly mobile students. This monograph will…

Demonstration of LenzÂ's law with an induction motor

NASA Astrophysics Data System (ADS)

Kraftmakher, Yaakov

2005-03-01

The interaction of a conductor with a time-dependent magnetic field is an important topic of electromagnetic theory. A computerized classroom demonstration shows how the eddy currents induced in the rotor of an induction motor cause its rotation or braking. Both phenomena are directly related to Lenz’s law.

A Novelty Design Of Minimization Of Electrical Losses In A Vector Controlled Induction Machine Drive

NASA Astrophysics Data System (ADS)

Aryza, Solly; Irwanto, M.; Lubis, Zulkarnain; Putera Utama Siahaan, Andysah; Rahim, Robbi; Furqan, Mhd.

2018-01-01

The induction motor has in the industry . More attention has been a focus to develop and design of induction motor drive. With the method of vector control novelty prove the efficiency of induction motor over their entire speed range. In this paper desirable to design a loss minimization controller which can improve the efficiency. Also, this research described Modeling of an induction motor with core loss included. Realization of methods vector control for an induction motor drive with loss element included. The case of the loss minimization condition. The procedure was successful to calculate the gains of a PI controller. Though the problem of obtaining a robust and sensorless induction motor drive is by no means completely solved, the results obtained as part of this work point in a promising direction.

Temperature-dependent innate defense against the common cold virus limits viral replication at warm temperature in mouse airway cells.

PubMed

Foxman, Ellen F; Storer, James A; Fitzgerald, Megan E; Wasik, Bethany R; Hou, Lin; Zhao, Hongyu; Turner, Paul E; Pyle, Anna Marie; Iwasaki, Akiko

2015-01-20

Most isolates of human rhinovirus, the common cold virus, replicate more robustly at the cool temperatures found in the nasal cavity (33-35 °C) than at core body temperature (37 °C). To gain insight into the mechanism of temperature-dependent growth, we compared the transcriptional response of primary mouse airway epithelial cells infected with rhinovirus at 33 °C vs. 37 °C. Mouse airway cells infected with mouse-adapted rhinovirus 1B exhibited a striking enrichment in expression of antiviral defense response genes at 37 °C relative to 33 °C, which correlated with significantly higher expression levels of type I and type III IFN genes and IFN-stimulated genes (ISGs) at 37 °C. Temperature-dependent IFN induction in response to rhinovirus was dependent on the MAVS protein, a key signaling adaptor of the RIG-I-like receptors (RLRs). Stimulation of primary airway cells with the synthetic RLR ligand poly I:C led to greater IFN induction at 37 °C relative to 33 °C at early time points poststimulation and to a sustained increase in the induction of ISGs at 37 °C relative to 33 °C. Recombinant type I IFN also stimulated more robust induction of ISGs at 37 °C than at 33 °C. Genetic deficiency of MAVS or the type I IFN receptor in infected airway cells permitted higher levels of viral replication, particularly at 37 °C, and partially rescued the temperature-dependent growth phenotype. These findings demonstrate that in mouse airway cells, rhinovirus replicates preferentially at nasal cavity temperature due, in part, to a less efficient antiviral defense response of infected cells at cool temperature.

Pharmacological activation of a novel p53-dependent S-phase checkpoint involving CHK-1

PubMed Central

Ahmed, A; Yang, J; Maya-Mendoza, A; Jackson, D A; Ashcroft, M

2011-01-01

We have recently shown that induction of the p53 tumour suppressor protein by the small-molecule RITA (reactivation of p53 and induction of tumour cell apoptosis; 2,5-bis(5-hydroxymethyl-2-thienyl)furan) inhibits hypoxia-inducible factor-1α and vascular endothelial growth factor expression in vivo and induces p53-dependent tumour cell apoptosis in normoxia and hypoxia. Here, we demonstrate that RITA activates the canonical ataxia telangiectasia mutated/ataxia telangiectasia and Rad3-related DNA damage response pathway. Interestingly, phosphorylation of checkpoint kinase (CHK)-1 induced in response to RITA was influenced by p53 status. We found that induction of p53, phosphorylated CHK-1 and γH2AX proteins was significantly increased in S-phase. Furthermore, we found that RITA stalled replication fork elongation, prolonged S-phase progression and induced DNA damage in p53 positive cells. Although CHK-1 knockdown did not significantly affect p53-dependent DNA damage or apoptosis induced by RITA, it did block the ability for DNA integrity to be maintained during the immediate response to RITA. These data reveal the existence of a novel p53-dependent S-phase DNA maintenance checkpoint involving CHK-1. PMID:21593792

Induction of autophagy by ARHI (DIRAS3) alters fundamental metabolic pathways in ovarian cancer models.

PubMed

Ornelas, Argentina; McCullough, Christopher R; Lu, Zhen; Zacharias, Niki M; Kelderhouse, Lindsay E; Gray, Joshua; Yang, Hailing; Engel, Brian J; Wang, Yan; Mao, Weiqun; Sutton, Margie N; Bhattacharya, Pratip K; Bast, Robert C; Millward, Steven W

2016-10-26

Autophagy is a bulk catabolic process that modulates tumorigenesis, therapeutic resistance, and dormancy. The tumor suppressor ARHI (DIRAS3) is a potent inducer of autophagy and its expression results in necroptotic cell death in vitro and tumor dormancy in vivo. ARHI is down-regulated or lost in over 60 % of primary ovarian tumors yet is dramatically up-regulated in metastatic disease. The metabolic changes that occur during ARHI induction and their role in modulating death and dormancy are unknown. We employed Nuclear Magnetic Resonance (NMR)-based metabolomic strategies to characterize changes in key metabolic pathways in both cell culture and xenograft models of ARHI expression and autophagy. These pathways were further interrogated by cell-based immunofluorescence imaging, tracer uptake studies, targeted metabolic inhibition, and in vivo PET/CT imaging. Induction of ARHI in cell culture models resulted in an autophagy-dependent increase in lactate production along with increased glucose uptake and enhanced sensitivity to glycolytic inhibitors. Increased uptake of glutamine was also dependent on autophagy and dramatically sensitized cultured ARHI-expressing ovarian cancer cell lines to glutaminase inhibition. Induction of ARHI resulted in a reduction in mitochondrial respiration, decreased mitochondrial membrane potential, and decreased Tom20 staining suggesting an ARHI-dependent loss of mitochondrial function. ARHI induction in mouse xenograft models resulted in an increase in free amino acids, a transient increase in [ 18 F]-FDG uptake, and significantly altered choline metabolism. ARHI expression has previously been shown to trigger autophagy-associated necroptosis in cell culture. In this study, we have demonstrated that ARHI expression results in decreased cellular ATP/ADP, increased oxidative stress, and decreased mitochondrial function. While this bioenergetic shock is consistent with programmed necrosis, our data indicates that the accompanying up-regulation of glycolysis and glutaminolysis is autophagy-dependent and serves to support cell viability rather than facilitate necroptotic cell death. While the mechanistic basis for metabolic up-regulation following ARHI induction is unknown, our preliminary data suggest that decreased mitochondrial function and increased metabolic demand may play a role. These alterations in fundamental metabolic pathways during autophagy-associated necroptosis may provide the basis for new therapeutic strategies for the treatment of dormant ovarian tumors.

Optimal Control of Induction Machines to Minimize Transient Energy Losses

NASA Astrophysics Data System (ADS)

Plathottam, Siby Jose

Induction machines are electromechanical energy conversion devices comprised of a stator and a rotor. Torque is generated due to the interaction between the rotating magnetic field from the stator, and the current induced in the rotor conductors. Their speed and torque output can be precisely controlled by manipulating the magnitude, frequency, and phase of the three input sinusoidal voltage waveforms. Their ruggedness, low cost, and high efficiency have made them ubiquitous component of nearly every industrial application. Thus, even a small improvement in their energy efficient tend to give a large amount of electrical energy savings over the lifetime of the machine. Hence, increasing energy efficiency (reducing energy losses) in induction machines is a constrained optimization problem that has attracted attention from researchers. The energy conversion efficiency of induction machines depends on both the speed-torque operating point, as well as the input voltage waveform. It also depends on whether the machine is in the transient or steady state. Maximizing energy efficiency during steady state is a Static Optimization problem, that has been extensively studied, with commercial solutions available. On the other hand, improving energy efficiency during transients is a Dynamic Optimization problem that is sparsely studied. This dissertation exclusively focuses on improving energy efficiency during transients. This dissertation treats the transient energy loss minimization problem as an optimal control problem which consists of a dynamic model of the machine, and a cost functional. The rotor field oriented current fed model of the induction machine is selected as the dynamic model. The rotor speed and rotor d-axis flux are the state variables in the dynamic model. The stator currents referred to as d-and q-axis currents are the control inputs. A cost functional is proposed that assigns a cost to both the energy losses in the induction machine, as well as the deviations from desired speed-torque-magnetic flux setpoints. Using Pontryagin's minimum principle, a set of necessary conditions that must be satisfied by the optimal control trajectories are derived. The conditions are in the form a two-point boundary value problem, that can be solved numerically. The conjugate gradient method that was modified using the Hestenes-Stiefel formula was used to obtain the numerical solution of both the control and state trajectories. Using the distinctive shape of the numerical trajectories as inspiration, analytical expressions were derived for the state, and control trajectories. It was shown that the trajectory could be fully described by finding the solution of a one-dimensional optimization problem. The sensitivity of both the optimal trajectory and the optimal energy efficiency to different induction machine parameters were analyzed. A non-iterative solution that can use feedback for generating optimal control trajectories in real time was explored. It was found that an artificial neural network could be trained using the numerical solutions and made to emulate the optimal control trajectories with a high degree of accuracy. Hence a neural network along with a supervisory logic was implemented and used in a real-time simulation to control the Finite Element Method model of the induction machine. The results were compared with three other control regimes and the optimal control system was found to have the highest energy efficiency for the same drive cycle.

THE EFFECTS OF DRONABINOL DURING DETOXIFICATION AND THE INITIATION OF TREATMENT WITH EXTENDED RELEASE NALTREXONE

PubMed Central

Bisaga, Adam; Sullivan, Maria A.; Glass, Andrew; Mishlen, Kaitlyn; Pavlicova, Martina; Haney, Margaret; Raby, Wilfrid N.; Levin, Frances R.; Carpenter, Kenneth M.; Mariani, John J.; Nunes, Edward V.

2015-01-01

Background Evidence suggests that the cannabinoid system is involved in the maintenance of opioid dependence. We examined whether dronabinol, a cannabinoid receptor type 1 partial agonist, reduces opioid withdrawal and increases retention in treatment with extended release naltrexone (XR-naltrexone). Methods Opioid dependent participants were randomized to receive dronabinol 30 mg/d (n=40) or placebo (n=20), under double-blind conditions, while they underwent inpatient detoxification and naltrexone induction. Before discharge all participants received an injection of XR-naltrexone, with an additional dose given four weeks later. Dronabinol or placebo was given while inpatient and for 5 weeks afterwards. The primary outcomes were the severity of opioid withdrawal, measured with the Subjective Opioid Withdrawal Scale, and retention in treatment at the end of the inpatient phase and at the end of the 8-week trial. Results The severity of opioid withdrawal during inpatient phase was lower in the dronabinol group relative to placebo group (p=0.006). Rates of successful induction onto XR-naltrexone (dronabinol 66%, placebo 55%) and completion of treatment (dronabinol 35%, placebo 35%) were not significantly different. Post-hoc analysis showed that the 32% of participants who smoked marijuana regularly during the outpatient phase had significantly lower ratings of insomnia and anxiety and were more likely to complete the 8-week trial. Conclusion Dronabinol reduced the severity of opiate withdrawal during acute detoxification but had no effect on rates of XR-naltrexone treatment induction and retention. Participants who elected to smoke marijuana during the trial were more likely to complete treatment regardless of treatment group assignment. PMID:26187456

Hints for cyclical recruitment of atelectasis during ongoing mechanical ventilation in lavage and oleic acid lung injury detected by SpO₂ oscillations and electrical impedance tomography.

PubMed

Bodenstein, Marc; Boehme, Stefan; Wang, Hemei; Duenges, Bastian; Markstaller, Klaus

2014-11-01

Detection of cyclical recruitment of atelectasis after induction of lavage (LAV) or oleic acid injury (OAI) in mechanically ventilated pigs. Primary hypothesis is that oxygen oscillations within the respiratory cycle can be detected by SpO₂ recordings (direct hint). SpO₂ oscillations reflect shunt oscillations that can only be explained by cyclical recruitment of atelectasis. Secondary hypothesis is that electrical impedance tomography (EIT) depicts specific regional changes of lung aeration and of pulmonary mechanical properties (indirect hint). Three groups (each n = 7) of mechanically ventilated pigs were investigated applying above mentioned methods before and repeatedly after induction of lung injury: (1) sham treated animals (SHAM), (2) LAV, and (3) OAI. Early oxygen oscillations occurred in the LAV group (mean calculated amplitude: 73.8 mmHg reflecting shunt oscillation of 11.2% in mean). In the OAI group oxygen oscillations occurred hours after induction of lung injury (mean calculated amplitude: 57.1 mmHg reflecting shunt oscillations of 8.4% in mean). The SHAM group had no relevant oxygen oscillations (<30 mmHg, shunt oscillations < 1.5%). Synchronously to oxygen oscillations, EIT depicted (1) a decrease of ventilation in dorsal areas, (2) an increase in ventral areas, (3) a decrease of especially dependent expiratory impedance, 3) an increase in late inspiratory flow especially in the dependant areas, (4) an increase in the speed of peak expiratory flow (PEF), and (5) a decrease of dorsal late expiratory flow. SpO2 and EIT recordings detect events that are interpreted as cyclical recruitment of atelectasis.

Numerical Studies of Three-dimensional Breakdown in Trailing Vortex Wakes

NASA Technical Reports Server (NTRS)

Evans, P. F.; Hackett, J. E.

1976-01-01

Finite element, three dimensional relaxation methods are used to calculate the development of vortex wakes behind aircraft for a considerable downstream distance. The inclusion of a self-induction term in the solution, dependent upon local curvature and vortex core radius, permits calculation of finite lifetimes for systems for which infinite life would be predicted two dimensionally. The associated computer program is described together with single-pair, twin-pair, and multiple-pair studies carried out using it. It is found, in single-pair studies, that there is a lower limit to the wavelengths at which the Crow-type of instability can occur. Below this limit, self-induction effects cause the plane of the disturbance waves to rotate counter to the vortex direction. Self induction in two dimensionally generated twin spiral waves causes an increase in axial length which becomes more marked with decreasing initial wavelength. The time taken for vortex convergence toward the center plane is correspondingly increased. The limited parametric twin-pair study performed suggests that time-to-converge increases with increasing flap span. Limited studies of Boeing 747 configurations show correct qualitative response to removal of the outer flap and to gear deployment, as compared with wind tunnel and flight test experience.

Synthesis of Multiwall Carbon Nanotubes by Inductive Heating CCVD

NASA Technical Reports Server (NTRS)

Biris, A. R.; Biris, A. S.; Lupu, D.; Trigwell, S.; Rahman, Z. U.; Aldea, N.; Marginean, P.

2005-01-01

The CCVD syntheses of MWCNTs from acetylene on Fe:Co:CaCO 3 and Fe:Co:CaO were performed using two different methods of heating: outer furnace and inductive heating. The comparative analysis of the MWCNTs obtained by the two methods show that the tubes grown in inductive heating have smaller diameters (5-25 nm), with fewer walls and aspect ratio of the order of hundreds. The ratio of outer to inner diameter (od/id) is ranging between 2 and 2.5. Inductively assisted CCVD is a very attractive method because of the major advantages that it presents, like low energetic consumption, thinner, well crystallized and more uniform tubes.

Article separation apparatus and method for unit operations

DOEpatents

Pardini, Allan F.; Gervais, Kevin L.; Mathews, Royce A.; Hockey, Ronald L.

2010-06-22

An apparatus and method are disclosed for separating articles from a group of articles. The apparatus includes a container for containing one or more articles coupled to a suitable fluidizer for suspending articles within the container and transporting articles to an induction tube. A portal in the induction tube introduces articles singly into the induction tube. A vacuum pulls articles through the induction tube separating the articles from the group of articles in the container. The apparatus and method can be combined with one or more unit operations or modules, e.g., for inspecting articles, assessing quality of articles, or ascertaining material properties and/or parameters of articles, including layers thereof.

Public sector low threshold office-based buprenorphine treatment: outcomes at year 7.

PubMed

Bhatraju, Elenore Patterson; Grossman, Ellie; Tofighi, Babak; McNeely, Jennifer; DiRocco, Danae; Flannery, Mara; Garment, Ann; Goldfeld, Keith; Gourevitch, Marc N; Lee, Joshua D

2017-02-28

Buprenorphine maintenance for opioid dependence remains of limited availability among underserved populations, despite increases in US opioid misuse and overdose deaths. Low threshold primary care treatment models including the use of unobserved, "home," buprenorphine induction may simplify initiation of care and improve access. Unobserved induction and long-term treatment outcomes have not been reported recently among large, naturalistic cohorts treated in low threshold safety net primary care settings. This prospective clinical registry cohort design estimated rates of induction-related adverse events, treatment retention, and urine opioid results for opioid dependent adults offered buprenorphine maintenance in a New York City public hospital primary care office-based practice from 2006 to 2013. This clinic relied on typical ambulatory care individual provider-patient visits, prescribed unobserved induction exclusively, saw patients no more than weekly, and did not require additional psychosocial treatment. Unobserved induction consisted of an in-person screening and diagnostic visit followed by a 1-week buprenorphine written prescription, with pamphlet, and telephone support. Primary outcomes analyzed were rates of induction-related adverse events (AE), week 1 drop-out, and long-term treatment retention. Factors associated with treatment retention were examined using a Cox proportional hazard model among inductions and all patients. Secondary outcomes included overall clinic retention, buprenorphine dosages, and urine sample results. Of the 485 total patients in our registry, 306 were inducted, and 179 were transfers already on buprenorphine. Post-induction (n = 306), week 1 drop-out was 17%. Rates of any induction-related AE were 12%; serious adverse events, 0%; precipitated withdrawal, 3%; prolonged withdrawal, 4%. Treatment retention was a median 38 weeks (range 0-320) for inductions, compared to 110 (0-354) weeks for transfers and 57 for the entire clinic population. Older age, later years of first clinic visit (vs. 2006-2007), and baseline heroin abstinence were associated with increased treatment retention overall. Unobserved "home" buprenorphine induction in a public sector primary care setting appeared a feasible and safe clinical practice. Post-induction treatment retention of a median 38 weeks was in line with previous naturalistic studies of real-world office-based opioid treatment. Low threshold treatment protocols, as compared to national guidelines, may compliment recently increased prescriber patient limits and expand access to buprenorphine among public sector opioid use disorder patients.

Characterisation of anifrolumab, a fully human anti-interferon receptor antagonist antibody for the treatment of systemic lupus erythematosus

PubMed Central

Rajan, Bhargavi; Zerrouki, Kamelia; Karnell, Jodi L; Sagar, Divya; Vainshtein, Inna; Farmer, Erika; Rosenthal, Kimberly; Morehouse, Chris; de los Reyes, Melissa; Schifferli, Kevin; Liang, Meina; Sanjuan, Miguel A; Sims, Gary P; Kolbeck, Roland

2018-01-01

Objective We investigated the mechanistic and pharmacological properties of anifrolumab, a fully human, effector-null, anti-type I interferon (IFN) alpha receptor 1 (IFNAR1) monoclonal antibody in development for SLE. Methods IFNAR1 surface expression and internalisation on human monocytes before and after exposure to anifrolumab were assessed using confocal microscopy and flow cytometry. The effects of anifrolumab on type I IFN pathway activation were assessed using signal transducer and activator of transcription 1 (STAT1) phosphorylation, IFN-stimulated response element–luciferase reporter cell assays and type I IFN gene signature induction. The ability of anifrolumab to inhibit plasmacytoid dendritic cell (pDC) function and plasma cell differentiation was assessed by flow cytometry and ELISA. Effector-null properties of anifrolumab were assessed in antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) assays with B cells. Results Anifrolumab reduced cell surface IFNAR1 by eliciting IFNAR1 internalisation. Anifrolumab blocked type I IFN-dependent STAT1 phosphorylation and IFN-dependent signalling induced by recombinant and pDC-derived type I IFNs and serum of patients with SLE. Anifrolumab suppressed type I IFN production by blocking the type I IFN autoamplification loop and inhibited proinflammatory cytokine induction and the upregulation of costimulatory molecules on stimulated pDCs. Blockade of IFNAR1 suppressed plasma cell differentiation in pDC/B cell co-cultures. Anifrolumab did not exhibit CDC or ADCC activity. Conclusions Anifrolumab potently inhibits type I IFN-dependent signalling, including the type I IFN autoamplification loop, and is a promising therapeutic for patients with SLE and other diseases that exhibit chronic dysfunctional type I IFN signalling. PMID:29644082

Isothiocyanates induce UGT1A1 in humanized UGT1 mice in a CAR dependent fashion that is highly dependent upon oxidative stress.

PubMed

Yoda, Emiko; Paszek, Miles; Konopnicki, Camille; Fujiwara, Ryoichi; Chen, Shujuan; Tukey, Robert H

2017-04-19

Isothiocyanates, such as phenethyl isothiocyanate (PEITC), are formed following the consumption of cruciferous vegetables and generate reactive oxygen species (ROS) that lead to the induction of cytoprotective genes such as the UDP-glucuronosyltransferases (UGTs). The induction of ROS activates the Nrf2-Keap 1 pathway leading to the induction of genes through antioxidant response elements (AREs). UGT1A1, the sole enzyme responsible for the metabolism of bilirubin, can be induced following activation of Nrf2. When neonatal humanized UGT1 (hUGT1) mice, which exhibit severe levels of total serum bilirubin (TSB) because of a developmental delay in expression of the UGT1A1 gene, were treated with PEITC, TSB levels were reduced. Liver and intestinal UGT1A1 were induced, along with murine CYP2B10, a consensus CAR target gene. In both neonatal and adult hUGT1/Car -/- mice, PEITC was unable to induce CYP2B10. A similar result was observed following analysis of UGT1A1 expression in liver. However, TSB levels were still reduced in hUGT1/Car -/- neonatal mice because of ROS induction of intestinal UGT1A1. When oxidative stress was blocked by exposing mice to N-acetylcysteine, induction of liver UGT1A1 and CYP2B10 by PEITC was prevented. Thus, new findings in this report link an important role in CAR activation that is dependent upon oxidative stress.

Inflammasome and Fas-Mediated IL-1β Contributes to Th17/Th1 Cell Induction in Pathogenic Bacterial Infection In Vivo.

PubMed

Uchiyama, Ryosuke; Yonehara, Shin; Taniguchi, Shun'ichiro; Ishido, Satoshi; Ishii, Ken J; Tsutsui, Hiroko

2017-08-01

CD4 + Th cells play crucial roles in orchestrating immune responses against pathogenic microbes, after differentiating into effector subsets. Recent research has revealed the importance of IFN-γ and IL-17 double-producing CD4 + Th cells, termed Th17/Th1 cells, in the induction of autoimmune and inflammatory diseases. In addition, Th17/Th1 cells are involved in the regulation of infection caused by the intracellular bacterium Mycobacterium tuberculosis in humans. However, the precise mechanism of Th17/Th1 induction during pathogen infection is unclear. In this study, we showed that the inflammasome and Fas-dependent IL-1β induces Th17/Th1 cells in mice, in response to infection with the pathogenic intracellular bacterium Listeria monocytogenes In the spleens of infected wild-type mice, Th17/Th1 cells were induced, and expressed T-bet and Rorγt. In Pycard -/- mice, which lack the adaptor molecule of the inflammasome (apoptosis-associated speck-like protein containing a caspase recruitment domain), Th17/Th1 induction was abolished. In addition, the Fas-mediated IL-1β production was required for Th17/Th1 induction during bacterial infection: Th17/Th1 induction was abolished in Fas -/- mice, whereas supplementation with recombinant IL-1β restored Th17/Th1 induction via IL-1 receptor 1 (IL-1R1), and rescued the mortality of Fas -/- mice infected with Listeria IL-1R1, but not apoptosis-associated speck-like protein containing a caspase recruitment domain or Fas on T cells, was required for Th17/Th1 induction, indicating that IL-1β stimulates IL-1R1 on T cells for Th17/Th1 induction. These results indicate that IL-1β, produced by the inflammasome and Fas-dependent mechanisms, contributes cooperatively to the Th17/Th1 induction during bacterial infection. This study provides a deeper understanding of the molecular mechanisms underlying Th17/Th1 induction during pathogenic microbial infections in vivo. Copyright © 2017 by The American Association of Immunologists, Inc.

40 CFR Appendix C to Part 136 - Inductively Coupled Plasma-Atomic Emission Spectrometric Method for Trace Element Analysis of...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Inductively Coupled Plasma-Atomic... to Part 136—Inductively Coupled Plasma—Atomic Emission Spectrometric Method for Trace Element... technique. Samples are nebulized and the aerosol that is produced is transported to the plasma torch where...

40 CFR Appendix C to Part 136 - Inductively Coupled Plasma-Atomic Emission Spectrometric Method for Trace Element Analysis of...

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 23 2011-07-01 2011-07-01 false Inductively Coupled Plasma-Atomic... to Part 136—Inductively Coupled Plasma—Atomic Emission Spectrometric Method for Trace Element... technique. Samples are nebulized and the aerosol that is produced is transported to the plasma torch where...

Mathematical Induction and Recursive Definition in Teaching Training

ERIC Educational Resources Information Center

Vármonostory, Endre

2009-01-01

The method of proof by mathematical induction follows from Peano axiom 5. We give three properties which are often used in the proofs by mathematical induction. We show that these are equivalent. Supposing the well-ordering property we prove the validity of this method without using Peano axiom 5. Finally, we introduce the simplest form of…

The Induction of Hyperthermia in Rabbit Liver by means of Duplex Stainless Steel Thermoseeds

PubMed Central

Koo, Bong Sig; Kim, Young Kon; Kim, Moon Kon

2002-01-01

Objective To determine the heating characteristics of needle-shaped duplex stainless steel thermoseeds, and to evaluate their effectiveness in the induction of hyperthermia in rabbit liver. Materials and Methods Thermoseeds of the two different shapes, L-shaped for single doses of hyperthermia and I-shaped for in-vitro study and repeated hyperthermic induction, were prepared. For the in-vitro study, an I-shaped thermoseed 0.23 mm in diameter and 25 mm long was placed inside a plastic tube filled with water. Heat was applied for 30 minutes within an induction magnetic field, and during this time changes in temperature were recorded using three thermocouples. For the in-vivo study, fifteen New Zealand white rabbits were divided into five equal groups. An I-shaped or L-shaped thermoseed was inserted in each rabbit's liver, and then placed within the center of the magnetic induction coil during a 30-minute period of hyperthermia. The rabbits in the first group were sacrificed immediately after hyperthermia was induced once, while those in the other groups were sacrificed at 1, 3, and 7 days, respectively, also after one induction. The remaining three rabbits were sacrificed 4 days after three consecutive daily treatment sessions. The resected segments of liver were subsequently evaluated histopathologically for the extent of coagulation necrosis caused by heating of the thermoseed. Results The in-vitro study demonstrated that the temperature in the thermoseed, which was 25.9℃ before heating and 54.8℃ after heating, rose rapidly at first but progressively less rapidly as time elapsed. Light microscopic examination of the rabbits' livers revealed coagulation necrosis and infiltration by inflammatory cells around the insertion site of the thermoseed. The maximum diameter of coagulation necrosis was 2.81 ± 1.68 mm, and this occurred in the rabbits that were sacrificed 7 days after heat induction. Conclusion Needle-shaped duplex stainless steel thermoseeds show temperature-dependent-type heating characteristics, and in rabbit liver, induced coagulation necrosis of surrounding tissues after heat is applied for 30 minutes. These thermoseeds may thus be useful for the induction of interstitial hyperthermia. PMID:12087199

Design of PCB search coils for AC magnetic flux density measurement

NASA Astrophysics Data System (ADS)

Ulvr, Michal

2018-04-01

This paper presents single-layer, double-layer and ten-layer planar square search coils designed for AC magnetic flux density amplitude measurement up to 1 T in the low frequency range in a 10 mm air gap. The printed-circuit-board (PCB) method was used for producing the search coils. Special attention is given to a full characterization of the PCB search coils including a comparison between the detailed analytical design method and the finite integration technique method (FIT) on the one hand, and experimental results on the other. The results show very good agreement in the resistance, inductance and search coil constant values (the area turns) and also in the frequency dependence of the search coil constant.

A Genetic Approach to Promoter Recognition during Trans Induction of Viral Gene Expression

NASA Astrophysics Data System (ADS)

Coen, Donald M.; Weinheimer, Steven P.; McKnight, Steven L.

1986-10-01

Viral infection of mammalian cells entails the regulated induction of viral gene expression. The induction of many viral genes, including the herpes simplex virus gene encoding thymidine kinase (tk), depends on viral regulatory proteins that act in trans. Because recognition of the tk promoter by cellular transcription factors is well understood, its trans induction by viral regulatory proteins may serve as a useful model for the regulation of eukaryotic gene expression. A comprehensive set of mutations was therefore introduced into the chromosome of herpes simplex virus at the tk promoter to directly analyze the effects of promoter mutations on tk transcription. The promoter domains required for efficient tk expression under conditions of trans induction corresponded to those important for recognition by cellular transcription factors. Thus, trans induction of tk expression may be catalyzed initially by the interaction of viral regulatory proteins with cellular transcription factors.

Induction of Viable but Nonculturable Salmonella in Exponentially Grown Cells by Exposure to a Low-Humidity Environment and Their Resuscitation by Catalase.

PubMed

Morishige, Yuta; Koike, Atsushi; Tamura-Ueyama, Ai; Amano, Fumio

2017-02-01

Salmonella is a major cause of foodborne disease that sometimes occurs in massive outbreaks around the world. This pathogen is tolerant of low-humidity conditions. We previously described a method for induction of viable but nonculturable (VBNC) Salmonella enterica serovar Enteritidis by treatment with hydrogen peroxide (H 2 O 2 ) and subsequent resuscitation with 0.3 mM sodium pyruvate. Here, we report a new method for the induction of the VBNC state in Salmonella Enteritidis cells, one involving dehydration. Exposure of Salmonella Enteritidis cells to dehydration stress under poor nutritional conditions (0.9% [wt/vol] NaCl) and 10 to 20% relative humidity at room temperature decreased the presence of culturable population to 0.0067%, but respiratory and glucose uptake active populations were maintained at 0.46 and 1.12%, respectively, meaning that approximately 1% may have entered the VBNC state. Furthermore, these VBNC cells could be resuscitated to acquire culturability by incubation with catalase in M9 minimal medium without glucose in a manner dependent on the dose of catalase but not sodium pyruvate. These results suggest that a low-humidity environment could cause Salmonella Enteritidis cells to enter the VBNC state and the cells could then be resuscitated for growth by treatment with catalase, suggesting a potential risk of Salmonella Enteritidis to survive in low water activity foods in the VBNC state and to start regrowth for foodborne illness.

Managing the SOS Response for Enhanced CRISPR-Cas-Based Recombineering in E. coli through Transient Inhibition of Host RecA Activity.

PubMed

Moreb, Eirik Adim; Hoover, Benjamin; Yaseen, Adam; Valyasevi, Nisakorn; Roecker, Zoe; Menacho-Melgar, Romel; Lynch, Michael D

2017-12-15

Phage-derived "recombineering" methods are utilized for bacterial genome editing. Recombineering results in a heterogeneous population of modified and unmodified chromosomes, and therefore selection methods, such as CRISPR-Cas9, are required to select for edited clones. Cells can evade CRISPR-Cas-induced cell death through recA-mediated induction of the SOS response. The SOS response increases RecA dependent repair as well as mutation rates through induction of the umuDC error prone polymerase. As a result, CRISPR-Cas selection is more efficient in recA mutants. We report an approach to inhibiting the SOS response and RecA activity through the expression of a mutant dominant negative form of RecA, which incorporates into wild type RecA filaments and inhibits activity. Using a plasmid-based system in which Cas9 and recA mutants are coexpressed, we can achieve increased efficiency and consistency of CRISPR-Cas9-mediated selection and recombineering in E. coli, while reducing the induction of the SOS response. To date, this approach has been shown to be independent of recA genotype and host strain lineage. Using this system, we demonstrate increased CRISPR-Cas selection efficacy with over 10 000 guides covering the E. coli chromosome. The use of dominant negative RecA or homologues may be of broad use in bacterial CRISPR-Cas-based genome editing where the SOS pathways are present.

Toward a Principled Sampling Theory for Quasi-Orders

PubMed Central

Ünlü, Ali; Schrepp, Martin

2016-01-01

Quasi-orders, that is, reflexive and transitive binary relations, have numerous applications. In educational theories, the dependencies of mastery among the problems of a test can be modeled by quasi-orders. Methods such as item tree or Boolean analysis that mine for quasi-orders in empirical data are sensitive to the underlying quasi-order structure. These data mining techniques have to be compared based on extensive simulation studies, with unbiased samples of randomly generated quasi-orders at their basis. In this paper, we develop techniques that can provide the required quasi-order samples. We introduce a discrete doubly inductive procedure for incrementally constructing the set of all quasi-orders on a finite item set. A randomization of this deterministic procedure allows us to generate representative samples of random quasi-orders. With an outer level inductive algorithm, we consider the uniform random extensions of the trace quasi-orders to higher dimension. This is combined with an inner level inductive algorithm to correct the extensions that violate the transitivity property. The inner level correction step entails sampling biases. We propose three algorithms for bias correction and investigate them in simulation. It is evident that, on even up to 50 items, the new algorithms create close to representative quasi-order samples within acceptable computing time. Hence, the principled approach is a significant improvement to existing methods that are used to draw quasi-orders uniformly at random but cannot cope with reasonably large item sets. PMID:27965601

Toward a Principled Sampling Theory for Quasi-Orders.

PubMed

Ünlü, Ali; Schrepp, Martin

2016-01-01

Quasi-orders, that is, reflexive and transitive binary relations, have numerous applications. In educational theories, the dependencies of mastery among the problems of a test can be modeled by quasi-orders. Methods such as item tree or Boolean analysis that mine for quasi-orders in empirical data are sensitive to the underlying quasi-order structure. These data mining techniques have to be compared based on extensive simulation studies, with unbiased samples of randomly generated quasi-orders at their basis. In this paper, we develop techniques that can provide the required quasi-order samples. We introduce a discrete doubly inductive procedure for incrementally constructing the set of all quasi-orders on a finite item set. A randomization of this deterministic procedure allows us to generate representative samples of random quasi-orders. With an outer level inductive algorithm, we consider the uniform random extensions of the trace quasi-orders to higher dimension. This is combined with an inner level inductive algorithm to correct the extensions that violate the transitivity property. The inner level correction step entails sampling biases. We propose three algorithms for bias correction and investigate them in simulation. It is evident that, on even up to 50 items, the new algorithms create close to representative quasi-order samples within acceptable computing time. Hence, the principled approach is a significant improvement to existing methods that are used to draw quasi-orders uniformly at random but cannot cope with reasonably large item sets.

Host manipulation by the orange leafhopper Cicadulina bipunctata: gall induction on distant leaves by dose-dependent stimulation

NASA Astrophysics Data System (ADS)

Matsukura, Keiichiro; Matsumura, Masaya; Tokuda, Makoto

2009-09-01

The evolution of the gall-inducing ability in insects and the adaptive significance of the galling habit have been addressed by many studies. Cicadulina bipunctata, the maize orange leafhopper, is an ideal study organism for evaluating these topics because it can be mass-reared and it feeds on model plants such as rice ( Oryza sativa) and maize ( Zea mays). To reveal differences between gall inductions by C. bipunctata and other gall inducers, we conducted four experiments concerning (a) the relationship between the feeding site and gall-induction sites of C. bipunctata on maize, (b) the effects of leafhopper sex and density, (c) the effects of length of infestation on gall induction, and (d) the effects of continuous infestation. C. bipunctata did not induce galls on the leaves where it fed but induced galls on other leaves situated at more distal positions. The degree of gall induction was significantly correlated with infestation density and length. These results indicate that C. bipunctata induces galls in a dose-dependent manner on leaves distant from feeding sites, probably by injecting chemical(s) to the plant during feeding. We suggest that insect galls are induced by a chemical stimulus injected by gall inducers during feeding into the hosts.

Induction of AID-targeting adaptor 14-3-3γ is mediated by NF-κB-dependent recruitment of CFP1 to the 5′-CpG-3′-rich 14-3-3γ promoter and is sustained by E2A

PubMed Central

Mai, Thach; Pone, Egest J.; Li, Guideng; Lam, Tonika S.; Moehlman, J’aime; Xu, Zhenming; Casali, Paolo

2013-01-01

Class switch DNA recombination (CSR) crucially diversifies antibody biological effectors functions. 14-3-3γ specifically binds to the 5′-AGCT-3′ repeats in the IgH locus switch (S) regions. By directly interacting with the C-terminal region of activation-induced cytidine deaminase (AID), 14-3-3γ targets this enzyme to S regions to mediate CSR. Here, we showed that 14-3-3γ was expressed in germinal center B cells in vivo and induced in B cells by T-dependent and T-independent primary CSR-inducing stimuli in vitro in humans and mice. Induction of 14-3-3γ was rapid, peaking within 3 h of stimulation by lipopolysaccharides (LPS), and sustained over the course of AID and CSR induction. It was dependent on recruitment of NF-κB to the 14-3-3γ gene promoter. The NF-κB recruitment enhanced the occupancy of the CpG island within the 14-3-3γ promoter by CFP1, a component of the COMPASS histone methyltransferase complex, and promoter-specific enrichment of histone 3 lysine 4 trimethylation (H3K4me3), which is indicative of open chromatin state and marks transcription-competent promoters. NF-κB also potentiated the binding of B cell lineage-specific factor E2A to an E-box motif located immediately downstream of the two closely-spaced transcription start sites (TSSs) for sustained 14-3-3γ expression and CSR induction. Thus, 14-3-3γ induction in CSR is enabled by the CFP1-mediated H3K4me3 enrichment in the promoter, dependent on NF-κB and sustained by E2A. PMID:23851690

Applications of rule-induction in the derivation of quantitative structure-activity relationships.

PubMed

A-Razzak, M; Glen, R C

1992-08-01

Recently, methods have been developed in the field of Artificial Intelligence (AI), specifically in the expert systems area using rule-induction, designed to extract rules from data. We have applied these methods to the analysis of molecular series with the objective of generating rules which are predictive and reliable. The input to rule-induction consists of a number of examples with known outcomes (a training set) and the output is a tree-structured series of rules. Unlike most other analysis methods, the results of the analysis are in the form of simple statements which can be easily interpreted. These are readily applied to new data giving both a classification and a probability of correctness. Rule-induction has been applied to in-house generated and published QSAR datasets and the methodology, application and results of these analyses are discussed. The results imply that in some cases it would be advantageous to use rule-induction as a complementary technique in addition to conventional statistical and pattern-recognition methods.

Applications of rule-induction in the derivation of quantitative structure-activity relationships

NASA Astrophysics Data System (ADS)

A-Razzak, Mohammed; Glen, Robert C.

1992-08-01

Recently, methods have been developed in the field of Artificial Intelligence (AI), specifically in the expert systems area using rule-induction, designed to extract rules from data. We have applied these methods to the analysis of molecular series with the objective of generating rules which are predictive and reliable. The input to rule-induction consists of a number of examples with known outcomes (a training set) and the output is a tree-structured series of rules. Unlike most other analysis methods, the results of the analysis are in the form of simple statements which can be easily interpreted. These are readily applied to new data giving both a classification and a probability of correctness. Rule-induction has been applied to in-house generated and published QSAR datasets and the methodology, application and results of these analyses are discussed. The results imply that in some cases it would be advantageous to use rule-induction as a complementary technique in addition to conventional statistical and pattern-recognition methods.

Gastrophysa polygoni herbivory on Rumex confertus: Single leaf VOC induction and dose dependent herbivore attraction/repellence to individual compounds

USDA-ARS?s Scientific Manuscript database

We report large induction (> 65fold increases) of volatile organic compounds (VOCs) emitted from a single leaf of the invasive weed mossy sorrel, Rumex confertus Willd. (Polygonaceae), by herbivory of the dock leaf beetle, Gastrophysa polygoni L. (Coleoptera: Chrysomelidae). The R. confertus VOC ble...

Characterization of virus/double-stranded RNA-dependent induction of antimicrobial peptide hepcidin in trout macrophages

USDA-ARS?s Scientific Manuscript database

Hepcidin is an antimicrobial peptide responsive to bacterial infection. We report the characterization of a virus/doublestranded RNA (dsRNA) induction of hepcidin in rainbow trout (Oncorhynchus mykiss). Increased level of hepcidin mRNA was observed in trout macrophage RTS11 cells treated with poly...

AN INTEGRATED PHARMACOKINETIC AND PHARMACODYNAMIC STUDY OF ARSENITE ACTION 2. HEME OXYGENASE INDUCTION IN MICE

EPA Science Inventory

Heme oxygenase (HO) is the rate-limiting enzyme in heme degradation and its activity has a significant impact on intracellular heme pools. Rat studies indicate that HO induction is a sensitive, dose-dependent response to arsenite (AsIII) exposure in both liver and kidney. The o...

38 CFR 21.370 - Intraregional travel at government expense.

Code of Federal Regulations, 2010 CFR

2010-07-01

... for a personal interview prior to induction into training when: (A) The school requires the interview... transportation for the veteran's dependents, or for moving personal effects. (Authority: 38 U.S.C. 111, 3104(a... report to a prospective employer-trainer for an interview prior to induction into training, when there is...

HALOGENATED AROMATIC HYDROCARBON-MEDIATED PORPHYRIN ACCUMULATION AND INDUCTION OF CYTOCHROME P4501A IN CHICKEN EMBRYO HEPATOCYTES. (R823889)

EPA Science Inventory

Concentration-dependent induction of cytochrome P4501A (CYP1A) and intracellular porphyrin accumulation were observed following treatment of chicken embryo hepatocyte (CEH) cultures with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,7,8-tetrachlorodibenzofuran (TCDF), 3,3',4,4'...

Structural Uncertainties in Numerical Induction Models

DTIC Science & Technology

2006-07-01

divide and conquer” modelling approach. Analytical inputs are then assessments, quantitative or qualitative, of the value, performance, or some...said to be naïve because it relies heavily on the inductive method itself. Sophisticated Induction (Logical Positivism ) This form of induction...falters. Popper’s Falsification Karl Popper around 1959 introduced a variant to the above Logical Positivism , known as the inductive-hypothetico

Energy saving concepts relating to induction generators

NASA Technical Reports Server (NTRS)

Nola, F. J.

1980-01-01

Energy saving concepts relating to induction generators are presented. The first describes a regenerative scheme using an induction generator as a variable load for prime movers under test is described. A method for reducing losses in induction machines used specifically as wind driven generators is also described.

Singer product apertures-A coded aperture system with a fast decoding algorithm

NASA Astrophysics Data System (ADS)

Byard, Kevin; Shutler, Paul M. E.

2017-06-01

A new type of coded aperture configuration that enables fast decoding of the coded aperture shadowgram data is presented. Based on the products of incidence vectors generated from the Singer difference sets, we call these Singer product apertures. For a range of aperture dimensions, we compare experimentally the performance of three decoding methods: standard decoding, induction decoding and direct vector decoding. In all cases the induction and direct vector methods are several orders of magnitude faster than the standard method, with direct vector decoding being significantly faster than induction decoding. For apertures of the same dimensions the increase in speed offered by direct vector decoding over induction decoding is better for lower throughput apertures.

Mechanically induced c-fos expression is mediated by cAMP in MC3T3-E1 osteoblasts

NASA Technical Reports Server (NTRS)

Fitzgerald, J.; Hughes-Fulford, M.

1999-01-01

In serum-deprived MC3T3-E1 osteoblasts, mechanical stimulation caused by mild (287 x g) centrifugation induced a 10-fold increase in mRNA levels of the proto-oncogene, c-fos. Induction of c-fos was abolished by the cAMP-dependent protein kinase inhibitor H-89, suggesting that the transient c-fos mRNA increase is mediated by cAMP. Down-regulation of protein kinase C (PKC) activity by chronic TPA treatment failed to significantly reduce c-fos induction, suggesting that TPA-sensitive isoforms of PKC are not responsible for c-fos up-regulation. In addition, 287 x g centrifugation increased intracellular prostaglandin E2 (PGE2) levels 2.8-fold (P<0. 005). Since we have previously shown that prostaglandin E2 (PGE2) can induce c-fos expression via a cAMP-mediated mechanism, we asked whether the increase in c-fos mRNA was due to centrifugation-induced PGE2 release. Pretreatment with the cyclooxygenase inhibitors indomethacin and flurbiprofen did not hinder the early induction of c-fos by mechanical stimulation. We conclude that c-fos expression induced by mild mechanical loading is dependent primarily on cAMP, not PKC, and initial induction of c-fos is not necessarily dependent on the action of newly synthesized PGE2.

Superconducting nanowires as nonlinear inductive elements for qubits

NASA Astrophysics Data System (ADS)

Ku, Jaseung; Manucharyan, Vladimir; Bezryadin, Alexey

2010-10-01

We report microwave transmission measurements of superconducting Fabry-Perot resonators, having a superconducting nanowire placed at a supercurrent antinode. As the plasma oscillation is excited, the supercurrent is forced to flow through the nanowire. The microwave transmission of the resonator-nanowire device shows a nonlinear resonance behavior, significantly dependent on the amplitude of the supercurrent oscillation. We show that such amplitude-dependent response is due to the nonlinearity of the current-phase relationship of the nanowire. The results are explained within a nonlinear oscillator model of the Duffing oscillator, in which the nanowire acts as a purely inductive element, in the limit of low temperatures and low amplitudes. The low-quality factor sample exhibits a “crater” at the resonance peak at higher driving power, which is due to dissipation. We observe a hysteretic bifurcation behavior of the transmission response to frequency sweep in a sample with a higher quality factor. The Duffing model is used to explain the Duffing bistability diagram. We also propose a concept of a nanowire-based qubit that relies on the current dependence of the kinetic inductance of a superconducting nanowire.

Analysis of mutagenic DNA repair in a thermoconditional mutant of Saccharomyces cerevisiae. IV. Influence of DNA replication and excision repair on REV2 dependent UV-mutagenesis and repair.

PubMed

Siede, W; Eckardt, F

1986-01-01

A double mutant being thermoconditionally defective in mutation induction as well as in repair of pre-lethal UV-induced DNA damage (rev2ts) and deficient in excision repair (rad3-2) was studied in temperature-shift experiments. The influence of inhibitors of DNA replication (hydroxyurea, aphidicolin) was determined. Additionally, an analysis of the dose-response pattern of mutation induction ("mutation kinetics") at several ochre alleles was carried out. It was concluded that the UV-inducible REV2 dependent mutagenic repair process is not induced in excision-deficient cells. In excision-deficient cells, REV2 dependent mutation fixation is slow and mostly post-replicative though not dependent on DNA replication. The REV2 mediated mutagenic process could be separated from the repair function.

Efficiency of the Lung Flute for sputum induction in patients with presumed pulmonary tuberculosis.

PubMed

Sakashita, Kentaro; Fujita, Akira; Takamori, Mikio; Nagai, Takayuki; Matsumoto, Tomoshige; Saito, Takefumi; Nakagawa, Taku; Ogawa, Kenji; Shigeto, Eriko; Nakatsumi, Yasuto; Goto, Hajime; Mitarai, Satoshi

2018-04-01

High quality sputum helps increase the sensitivity of the diagnosis of pulmonary tuberculosis. To evaluate the efficiency of the acoustic device (Lung Flute; LF) in sputum induction compared with the conventional method, hypertonic saline inhalation (HSI). In this crossover study, patients with presumed pulmonary tuberculosis submitted 3 consecutive sputa: the first sputum without induction and the second and third ones using LF and HSI. We compared the efficiency of the 2 induction methods. Sixty-four participants were eligible. Thirty-five (54.6%) patients had negative smears on the first sputum without induction. Among those patients, 25.7% and 22.9% patients were smear-positive after using LF and HSI, respectively (P = .001). The positive conversion rate was not significantly different between the methods. The first samples without induction yielded 65.7% positive cultures, whereas 71.4% and 77.1% of the samples from LF and HSI were positive, respectively (P = .284). Similar results were observed in the nucleic acid amplification test [no induction (60.0%), LF (72.0%) and HSI (60.0%); P = .341]. In 29 smear-positive patients on the first sputum without induction, we observed no significant increase in smear grade, culture yield and nucleic acid amplification test positivity with either method. LF tended to induce fewer adverse events; desaturation (3.1% vs 11.1%; P = .082) and throat pain (1.5% vs 9.5%; P = .057). LF showed significantly fewer total adverse events (15.8% vs 34.9%; P = .023). Our study showed LF had similar sputum induction efficiency to HSI with relatively fewer complications. © 2017 The Authors. The Clinical Respiratory Journal Published by John Wiley & Sons Ltd.

Enhanced expression of rat hepatic CYP2B1/2B2 and 2E1 by pyridine: differential induction kinetics and molecular basis of expression.

PubMed

Kim, H; Putt, D; Reddy, S; Hollenberg, P F; Novak, R F

1993-11-01

Expression of the cytochrome P450 (CYP) 2B subfamily in rat and rabbit hepatic tissues after pyridine (PY) treatment has been examined, and the molecular basis for enhanced 2B1/2B2 expression has been determined. P450 expression was monitored using metabolic activity, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblot analyses, and the identity of the proteins was confirmed through N-terminus microsequence analysis. PY caused a dose-dependent elevation of hepatic CYP2B1/B2B levels in rats, which ranged from 4- to 22-fold over the dosing regimen of 100 to 400 mg PY/kg/day, for 3 days, respectively. PY at low dose failed to induce CYP2B in rabbit hepatic tissue, suggesting a species-dependent response in 2B expression. Anti-2B1 IgG addition to PY-induced microsomes inhibited benzphetamine N-demethylase activity by only approximately 15%, in sharp contrast to the approximately 73% inhibition observed for phenobarbital-induced microsomes, suggesting the induction of other form(s) of P450 having benzphetamine N-demethylase activity. Northern blot analysis revealed that PY treatment increased 2B1 and 2B2 poly(A)+ RNA levels approximately 69- and approximately 34-fold, respectively, whereas the 2E1 poly(A)+ RNA levels failed to increase. The results of this study show that PY induces CYP2B1/2B2 and that induction is species-dependent and kinetically distinguishable from 2E1 induction. Moreover, 2B1/2B2 induction occurs as a result of elevated mRNA levels associated with either transcriptional activation or mRNA stabilization, and it differs from the mechanism of hepatic 2E1 induction by PY.

A Double Layer Model of the Electromagnetic and Thermal Processes in Induction Heating of Ferromagnetic Material

NASA Astrophysics Data System (ADS)

Gilev, B.; Kraev, G.; Venkov, G. I.

2007-10-01

This paper presents the modeling of electromagnetic and heating processes in an inductor, where cylindrical ferromagnetic material has been placed. In the first part the electromagnetic mathematical problem is solved, as a result the power density is obtained. The power density takes part in the heat conduction equation. In the second part the thermal mathematical problem is solved, as a result the alteration of the temperature of the ferromagnetic material during the heating process is obtained. The parameters in both mathematical problems depend on the temperature. Because of that the stitching method is used for their finding. In [3, 4] the same mathematical problems are solved by the finite elements method. Comparing our results to those from [3] shows that they are similar. In contrast to [3, 4] our method allows the continuation of the analysis with the finding of the load power during the heating process. Thus result permits the determination of the load power alteration in the supplying inverter [1]. It is well-known that during the induction hardening it is necessary to maintain constant current amplitude in the load circuit of the inverter. So the next aim of this research is to build up a controller, based on the developed model, which will procure the necessary mode.

Exploring help-seeking for ADHD symptoms: a mixed-methods approach.

PubMed

Bussing, Regina; Koro-Ljungberg, Mirka E; Gary, Faye; Mason, Dana M; Garvan, Cynthia W

2005-01-01

Gender and race differences in treatment rates for attention-deficit/hyperactivity disorder (ADHD) are well documented but poorly understood. Using a mixed-methods approach, this study examines parental help-seeking steps for elementary school students at high risk for ADHD. Parents of 259 students (male/female, African American/Caucasian) identified as being at high risk for ADHD completed diagnostic interviews and provided detailed accounts of help-seeking activities since they first became concerned about their child. Help-seeking steps (n=1,590) were analyzed using two methods: inductive analysis based on grounded theory, and deductive quantitative analysis of coded data derived from application of the network-episode model, merged subsequently with demographic and other characteristics. The inductive analysis revealed unique parental perceptions of their children's sick role and of the agents of identification and intervention for each of the four groups. Deductive analysis showed significant variations by race and gender in consultation experiences, in the person or entity being consulted and in the transactions occurring in the consultation, and in illness careers. ADHD symptoms are interpreted as having different implications for the sick role and the intervention, dependent on a child's gender and race. Educational interventions need to address cultural stereotypes contributing to inequitable access to treatment.

Induction of belief decision trees from data

NASA Astrophysics Data System (ADS)

AbuDahab, Khalil; Xu, Dong-ling; Keane, John

2012-09-01

In this paper, a method for acquiring belief rule-bases by inductive inference from data is described and evaluated. Existing methods extract traditional rules inductively from data, with consequents that are believed to be either 100% true or 100% false. Belief rules can capture uncertain or incomplete knowledge using uncertain belief degrees in consequents. Instead of using singled-value consequents, each belief rule deals with a set of collectively exhaustive and mutually exclusive consequents. The proposed method extracts belief rules from data which contain uncertain or incomplete knowledge.

Limited hair cell induction from human induced pluripotent stem cells using a simple stepwise method.

PubMed

Ohnishi, Hiroe; Skerleva, Desislava; Kitajiri, Shin-ichiro; Sakamoto, Tatsunori; Yamamoto, Norio; Ito, Juichi; Nakagawa, Takayuki

2015-07-10

Disease-specific induced pluripotent stem cells (iPS) cells are expected to contribute to exploring useful tools for studying the pathophysiology of inner ear diseases and to drug discovery for treating inner ear diseases. For this purpose, stable induction methods for the differentiation of human iPS cells into inner ear hair cells are required. In the present study, we examined the efficacy of a simple induction method for inducing the differentiation of human iPS cells into hair cells. The induction of inner ear hair cell-like cells was performed using a stepwise method mimicking inner ear development. Human iPS cells were sequentially transformed into the preplacodal ectoderm, otic placode, and hair cell-like cells. As a first step, preplacodal ectoderm induction, human iPS cells were seeded on a Matrigel-coated plate and cultured in a serum free N2/B27 medium for 8 days according to a previous study that demonstrated spontaneous differentiation of human ES cells into the preplacodal ectoderm. As the second step, the cells after preplacodal ectoderm induction were treated with basic fibroblast growth factor (bFGF) for induction of differentiation into otic-placode-like cells for 15 days. As the final step, cultured cells were incubated in a serum free medium containing Matrigel for 48 days. After preplacodal ectoderm induction, over 90% of cultured cells expressed the genes that express in preplacodal ectoderm. By culture with bFGF, otic placode marker-positive cells were obtained, although their number was limited. Further 48-day culture in serum free media resulted in the induction of hair cell-like cells, which expressed a hair cell marker and had stereocilia bundle-like constructions on their apical surface. Our results indicate that hair cell-like cells are induced from human iPS cells using a simple stepwise method with only bFGF, without the use of xenogeneic cells. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The myth of induction in qualitative nursing research.

PubMed

Bergdahl, Elisabeth; Berterö, Carina M

2015-04-01

In nursing today, it remains unclear what constitutes a good foundation for qualitative scientific inquiry. There is a tendency to define qualitative research as a form of inductive inquiry; deductive practice is seldom discussed, and when it is, this usually occurs in the context of data analysis. We will look at how the terms 'induction' and 'deduction' are used in qualitative nursing science and by qualitative research theorists, and relate these uses to the traditional definitions of these terms by Popper and other philosophers of science. We will also question the assertion that qualitative research is or should be inductive. The position we defend here is that qualitative research should use deductive methods. We also see a need to understand the difference between the creative process needed to create theory and the justification of a theory. Our position is that misunderstandings regarding the philosophy of science and the role of inductive and deductive logic and science are still harming the development of nursing theory and science. The purpose of this article is to discuss and reflect upon inductive and deductive views of science as well as inductive and deductive analyses in qualitative research. We start by describing inductive and deductive methods and logic from a philosophy of science perspective, and we examine how the concepts of induction and deduction are often described and used in qualitative methods and nursing research. Finally, we attempt to provide a theoretical perspective that reconciles the misunderstandings regarding induction and deduction. Our conclusion is that openness towards deductive thinking and testing hypotheses is needed in qualitative nursing research. We must also realize that strict induction will not create theory; to generate theory, a creative leap is needed. © 2014 John Wiley & Sons Ltd.

Effects of inductive bias on computational evaluations of ligand-based modeling and on drug discovery

NASA Astrophysics Data System (ADS)

Cleves, Ann E.; Jain, Ajay N.

2008-03-01

Inductive bias is the set of assumptions that a person or procedure makes in making a prediction based on data. Different methods for ligand-based predictive modeling have different inductive biases, with a particularly sharp contrast between 2D and 3D similarity methods. A unique aspect of ligand design is that the data that exist to test methodology have been largely man-made, and that this process of design involves prediction. By analyzing the molecular similarities of known drugs, we show that the inductive bias of the historic drug discovery process has a very strong 2D bias. In studying the performance of ligand-based modeling methods, it is critical to account for this issue in dataset preparation, use of computational controls, and in the interpretation of results. We propose specific strategies to explicitly address the problems posed by inductive bias considerations.

Coupling and power transfer efficiency enhancement of modular and array of planar coils using in-plane ring-shaped inner ferrites for inductive heating applications

NASA Astrophysics Data System (ADS)

Kilic, V. T.; Unal, E.; Demir, H. V.

2017-07-01

We propose and demonstrate a highly effective method of enhancing coupling and power transfer efficiency in inductive heating systems composed of planar coils. The proposed method is based on locating ring-shaped ferrites in the inner side of the coils in the same plane. Measurement results of simple inductive heating systems constructed with either a single or a pair of conventional circular coils show that, with the in-plane inner ferrites, the total dissipated power of the system is increased by over 65%. Also, with three-dimensional full electromagnetic solutions, it is found that power transfer efficiency of the system is increased up to 92% with the inner ferrite placement. The proposed method is promising to be used for efficiency enhancement in inductive heating applications, especially in all-surface induction hobs.

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

Bowman, Adam J.; Scherrer, Joseph R.; Reiserer, Ronald S., E-mail: ron.reiserer@vanderbilt.edu

We present a simple apparatus for improved surface modification of polydimethylsiloxane (PDMS) microfluidic devices. A single treatment chamber for plasma activation and chemical/physical vapor deposition steps minimizes the time-dependent degradation of surface activation that is inherent in multi-chamber techniques. Contamination and deposition irregularities are also minimized by conducting plasma activation and treatment phases in the same vacuum environment. An inductively coupled plasma driver allows for interchangeable treatment chambers. Atomic force microscopy confirms that silane deposition on PDMS gives much better surface quality than standard deposition methods, which yield a higher local roughness and pronounced irregularities in the surface.

A new electromagnetic NDI-technique based on the measurement of source-sample reaction forces

NASA Astrophysics Data System (ADS)

Fitzpatrick, G. L.; Skaugset, R. L.; Shih, W. C. L.

2001-04-01

Faraday's law of induction, Lenz's law, the Lorentz force law and Newton's third law, taken together, insure that sources (e.g., coil sources) of time-dependent electromagnetic fields, and nearby "nonmagnetic" electrical conductors (e.g., aluminum), always experience mutually repulsive (source-conductor) forces. This fact forms the basis for a new method for detecting cracks and corrosion in (aging) multi-layer airframes. The presence of cracks or corrosion (e.g., material thinning) in these structures is observed to reduce (second-harmonic) source-conductor reaction forces.

Harmonic reduction of Direct Torque Control of six-phase induction motor.

PubMed

Taheri, A

2016-07-01

In this paper, a new switching method in Direct Torque Control (DTC) of a six-phase induction machine for reduction of current harmonics is introduced. Selecting a suitable vector in each sampling period is an ordinal method in the ST-DTC drive of a six-phase induction machine. The six-phase induction machine has 64 voltage vectors and divided further into four groups. In the proposed DTC method, the suitable voltage vectors are selected from two vector groups. By a suitable selection of two vectors in each sampling period, the harmonic amplitude is decreased more, in and various comparison to that of the ST-DTC drive. The harmonics loss is greater reduced, while the electromechanical energy is decreased with switching loss showing a little increase. Spectrum analysis of the phase current in the standard and new switching table DTC of the six-phase induction machine and determination for the amplitude of each harmonics is proposed in this paper. The proposed method has a less sampling time in comparison to the ordinary method. The Harmonic analyses of the current in the low and high speed shows the performance of the presented method. The simplicity of the proposed method and its implementation without any extra hardware is other advantages of the proposed method. The simulation and experimental results show the preference of the proposed method. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

Agricultural Geophysics

USDA-ARS?s Scientific Manuscript database

The four geophysical methods predominantly used for agricultural purposes are resistivity, electromagnetic induction, ground penetrating radar (GPR), and time domain reflectometry (TDR). Resistivity and electromagnetic induction methods are typically employed to map lateral variations of apparent so...

Low-noise magnetometer based on inductance modulation in high-critical-temperature superconductor coil

NASA Astrophysics Data System (ADS)

Enpuku, Keiji; Matsuo, Masaaki; Yoshida, Yujiro; Yamashita, Shigeya; Sasayama, Teruyoshi; Yoshida, Takashi

2018-06-01

We developed a magnetometer based on inductance modulation of a coil made from a high-critical-temperature superconducting material. The coil inductance was modulated over time via a modulation current applied to a magnetic wire that was inserted into the coil. The magnetic field was then converted into a signal voltage using this time-dependent inductance. The relationship between magnetometer performance and the modulation current conditions was studied. Under appropriate conditions, the magnetometer had responsivity of 885 V/T. The magnetic field noise was 1.3 pT/Hz1/2 in the white noise region and 5.6 pT/Hz1/2 at f = 1 Hz.

Numerical Simulation of Induction Channel Furnace to Investigate Efficiency for low Frequencies

NASA Astrophysics Data System (ADS)

Hang, N. Tran Thi; Lüdtke, U.

2018-05-01

The foundry industry worldwide commonly uses induction channel furnaces to heat and melt alloys. The operating frequency is one of the main issues when constructing an efficient channel furnace. It is possible to choose operating frequencies lower than 50 Hz using a modern IGBT power converter. This work shows the simulation results using ANSYS with the goal of finding the best electrical frequency necessary to operate the induction furnace. First, a two-dimensional model is used to calculate the efficiency depending on frequency. Then, the channel model is extended to a more realistic three-dimensional model. Finally, the influence of frequency, inductor profile, and several components of the induction channel furnace are discussed.

Below-ground herbivory limits induction of extrafloral nectar by above-ground herbivores

PubMed Central

Huang, Wei; Siemann, Evan; Carrillo, Juli; Ding, Jianqing

2015-01-01

Background and Aims Many plants produce extrafloral nectar (EFN), and increase production following above-ground herbivory, presumably to attract natural enemies of the herbivores. Below-ground herbivores, alone or in combination with those above ground, may also alter EFN production depending on the specificity of this defence response and the interactions among herbivores mediated through plant defences. To date, however, a lack of manipulative experiments investigating EFN production induced by above- and below-ground herbivory has limited our understanding of how below-ground herbivory mediates indirect plant defences to affect above-ground herbivores and their natural enemies. Methods In a greenhouse experiment, seedlings of tallow tree (Triadica sebifera) were subjected to herbivory by a specialist flea beetle (Bikasha collaris) that naturally co-occurs as foliage-feeding adults and root-feeding larvae. Seedlings were subjected to above-ground adults and/or below-ground larvae herbivory, and EFN production was monitored. Key Results Above- and/or below-ground herbivory significantly increased the percentage of leaves with active nectaries, the volume of EFN and the mass of soluble solids within the nectar. Simultaneous above- and below-ground herbivory induced a higher volume of EFN and mass of soluble solids than below-ground herbivory alone, but highest EFN production was induced by above-ground herbivory when below-ground herbivores were absent. Conclusions The induction of EFN production by below-ground damage suggests that systemic induction underlies some of the EFN response. The strong induction by above-ground herbivory in the absence of below-ground herbivory points to specific induction based on above- and below-ground signals that may be adaptive for this above-ground indirect defence. PMID:25681822

Diurnal Emotional States Impact the Sleep Course

PubMed Central

Delannoy, Julien; Mandai, Osamu; Honoré, Jacques; Kobayashi, Toshinori; Sequeira, Henrique

2015-01-01

Background Diurnal emotional experiences seem to affect several characteristics of sleep architecture. However, this influence remains unclear, especially for positive emotions. In addition, electrodermal activity (EDA), a sympathetic robust indicator of emotional arousal, differs depending on the sleep stage. The present research has a double aim: to identify the specific effects of pre-sleep emotional states on the architecture of the subsequent sleep period; to relate such states to the sympathetic activation during the same sleep period. Methods Twelve healthy volunteers (20.1 ± 1.0 yo.) participated in the experiment and each one slept 9 nights at the laboratory, divided into 3 sessions, one per week. Each session was organized over three nights. A reference night, allowing baseline pre-sleep and sleep recordings, preceded an experimental night before which participants watched a negative, neutral, or positive movie. The third and last night was devoted to analyzing the potential recovery or persistence of emotional effects induced before the experimental night. Standard polysomnography and EDA were recorded during all the nights. Results Firstly, we found that experimental pre-sleep emotional induction increased the Rapid Eye Movement (REM) sleep rate following both negative and positive movies. While this increase was spread over the whole night for positive induction, it was limited to the second half of the sleep period for negative induction. Secondly, the valence of the pre-sleep movie also impacted the sympathetic activation during Non-REM stage 3 sleep, which increased after negative induction and decreased after positive induction. Conclusion Pre-sleep controlled emotional states impacted the subsequent REM sleep rate and modulated the sympathetic activity during the sleep period. The outcomes of this study offer interesting perspectives related to the effect of diurnal emotional influences on sleep regulation and open new avenues for potential practices designed to alleviate sleep disturbances. PMID:26606526

Post-electroconvulsive therapy recovery and reorientation time with methohexital and ketamine: a randomized, longitudinal cross-over design trial

PubMed Central

Yen, Tony; Khafaja, Mohamad; Lam, Nicholas; Crumbacher, James; Schrader, Ronald; Rask, John; Billstrand, Mary; Rothfork, Jacob; Abbott, Christopher C.

2014-01-01

Objectives Methohexital, a barbiturate anesthetic commonly used for electroconvulsive therapy (ECT), possesses dose-dependent anticonvulsant properties, and its use can interfere with effective seizure therapy in patients with high seizure thresholds. Ketamine, a NMDA-antagonist with epileptogenic properties not broadly used for ECT inductions, is a commonly used induction agent for general anesthesia. Recent studies suggest that the use of ketamine is effective in allowing successful ECT treatment in patients with high seizure thresholds without an increase in side-effects. In this preliminary study, we directly compared the recovery and re-orientation times of subjects receiving ketamine and methohexital for ECTs. Methods Twenty patients were randomized in a cross-over design to receive methohexital and ketamine for ECT inductions in alternating fashion for six trials. Primary outcome measures were recovery time (voluntary movement, respiratory effort, blood pressure, consciousness, and O2 saturation) and re-orientation time. Secondary outcome measures were individual recovery variables, side-effect occurrence, and seizure duration. Results: Overall recovery time was not significantly different between the two treatment arms (F(1,17) = 0.72, P = 0.41). Re-orientation time was faster in the methohexital arm (F(1,17) = 9.23, P = 0.007). Conclusion Ketamine inductions resulted in higher number of side-effects, higher subject dropout rates, and a longer reorientation time with respect to methohexital inductions. No significant difference in post-anesthesia recovery time was found between the ketamine and methohexital arms. Intolerability to ketamine affected a significant proportion of subjects, and suggests that ketamine should remain as an alternative or adjunctive agent for patients with high seizure thresholds. PMID:24755722

Characterization of Gonadotrope Secretoproteome Identifies Neurosecretory Protein VGF-derived Peptide Suppression of Follicle-stimulating Hormone Gene Expression.

PubMed

Choi, Soon Gang; Wang, Qian; Jia, Jingjing; Chikina, Maria; Pincas, Hanna; Dolios, Georgia; Sasaki, Kazuki; Wang, Rong; Minamino, Naoto; Salton, Stephen R J; Sealfon, Stuart C

2016-09-30

Reproductive function is controlled by the pulsatile release of hypothalamic gonadotropin-releasing hormone (GnRH), which regulates the expression of the gonadotropins luteinizing hormone and FSH in pituitary gonadotropes. Paradoxically, Fshb gene expression is maximally induced at lower frequency GnRH pulses, which provide a very low average concentration of GnRH stimulation. We studied the role of secreted factors in modulating gonadotropin gene expression. Inhibition of secretion specifically disrupted gonadotropin subunit gene regulation but left early gene induction intact. We characterized the gonadotrope secretoproteome and global mRNA expression at baseline and after Gα s knockdown, which has been found to increase Fshb gene expression (1). We identified 1077 secreted proteins or peptides, 19 of which showed mRNA regulation by GnRH or/and Gα s knockdown. Among several novel secreted factors implicated in Fshb gene regulation, we focused on the neurosecretory protein VGF. Vgf mRNA, whose gene has been implicated in fertility (2), exhibited high induction by GnRH and depended on Gα s In contrast with Fshb induction, Vgf induction occurred preferentially at high GnRH pulse frequency. We hypothesized that a VGF-derived peptide might regulate Fshb gene induction. siRNA knockdown or extracellular immunoneutralization of VGF augmented Fshb mRNA induction by GnRH. GnRH stimulated the secretion of the VGF-derived peptide NERP1. NERP1 caused a concentration-dependent decrease in Fshb gene induction. These findings implicate a VGF-derived peptide in selective regulation of the Fshb gene. Our results support the concept that signaling specificity from the cell membrane GnRH receptor to the nuclear Fshb gene involves integration of intracellular signaling and exosignaling regulatory motifs. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Characterization of Gonadotrope Secretoproteome Identifies Neurosecretory Protein VGF-derived Peptide Suppression of Follicle-stimulating Hormone Gene Expression*

PubMed Central

Wang, Qian; Jia, Jingjing; Chikina, Maria; Pincas, Hanna; Dolios, Georgia; Sasaki, Kazuki; Wang, Rong; Minamino, Naoto; Sealfon, Stuart C.

2016-01-01

Reproductive function is controlled by the pulsatile release of hypothalamic gonadotropin-releasing hormone (GnRH), which regulates the expression of the gonadotropins luteinizing hormone and FSH in pituitary gonadotropes. Paradoxically, Fshb gene expression is maximally induced at lower frequency GnRH pulses, which provide a very low average concentration of GnRH stimulation. We studied the role of secreted factors in modulating gonadotropin gene expression. Inhibition of secretion specifically disrupted gonadotropin subunit gene regulation but left early gene induction intact. We characterized the gonadotrope secretoproteome and global mRNA expression at baseline and after Gαs knockdown, which has been found to increase Fshb gene expression (1). We identified 1077 secreted proteins or peptides, 19 of which showed mRNA regulation by GnRH or/and Gαs knockdown. Among several novel secreted factors implicated in Fshb gene regulation, we focused on the neurosecretory protein VGF. Vgf mRNA, whose gene has been implicated in fertility (2), exhibited high induction by GnRH and depended on Gαs. In contrast with Fshb induction, Vgf induction occurred preferentially at high GnRH pulse frequency. We hypothesized that a VGF-derived peptide might regulate Fshb gene induction. siRNA knockdown or extracellular immunoneutralization of VGF augmented Fshb mRNA induction by GnRH. GnRH stimulated the secretion of the VGF-derived peptide NERP1. NERP1 caused a concentration-dependent decrease in Fshb gene induction. These findings implicate a VGF-derived peptide in selective regulation of the Fshb gene. Our results support the concept that signaling specificity from the cell membrane GnRH receptor to the nuclear Fshb gene involves integration of intracellular signaling and exosignaling regulatory motifs. PMID:27466366

Activation of cAMP-dependent signaling pathway induces mouse organic anion transporting polypeptide 2 expression.

PubMed

Chen, Chuan; Cheng, Xingguo; Dieter, Matthew Z; Tanaka, Yuji; Klaassen, Curtis D

2007-04-01

Rodent Oatp2 is a hepatic uptake transporter for such compounds as cardiac glycosides. In the present study, we found that fasting resulted in a 2-fold induction of Oatp2 expression in liver of mice. Because the cAMP-protein kinase A (PKA) signaling pathway is activated during fasting, the role of this pathway in Oatp2 induction during fasting was examined. In Hepa-1c1c7 cells, adenylyl cyclase activator forskolin as well as two cellular membrane-permeable cAMP analogs, dibutyryl cAMP and 8-bromo-cAMP, induced Oatp2 mRNA expression in a time- and dose-dependent manner. These three chemicals induced reporter gene activity in cells transfected with a luciferase reporter gene construct containing a 7.6-kilobase (kb) 5'-flanking region of mouse Oatp2. Transient transfection of cells with 5'-deletion constructs derived from the 7.6-kb Oatp2 promoter reporter gene construct, as well as 7.6-kb constructs in which a consensus cAMP response element (CRE) half-site CGTCA (-1808/-1804 bp) was mutated or deleted, confirms that this CRE site was required for the induction of luciferase activity by forskolin. Luciferase activity driven by the Oatp2 promoter containing this CRE site was induced in cells cotransfected with a plasmid encoding the protein kinase A catalytic subunit. Cotransfection of cells with a plasmid encoding the dominant-negative CRE binding protein (CREB) completely abolished the inducibility of the reporter gene activity by forskolin. In conclusion, induction of Oatp2 expression in liver of fasted mice may be caused by activation of the cAMP-dependent signaling pathway, with the CRE site (-1808/-1804) and CREB being the cis- and trans-acting factors mediating the induction, respectively.

Multiple interactions between maternally-activated signalling pathways control Xenopus nodal-related genes.

PubMed

Rex, Maria; Hilton, Emma; Old, Robert

2002-03-01

We have investigated the induction of the six Xenopus nodal-related genes, Xnr1-Xnr6, by maternal determinants. The beta-catenin pathway was modelled by stimulation using Xwnt8, activin-like signalling was modelled by activin, and VegT action was studied by overexpression in animal cap explants. Combinations of factors were examined, and previously unrecognised interactions were revealed in animal caps and whole embryos. For the induction of Xnr5 and Xnr6 in whole embryos, using a beta-catenin antisense morpholino oligonucleotide or a dominant negative XTcf3, we have demonstrated an absolute permissive requirement for the beta-catenin/Tcf pathway, in addition to the requirement for VegT action. In animal caps Xnr5 and Xnr6 are induced in response to VegT overexpression, and this induction is dependent upon the concomitant activation of the beta-catenin pathway that VegT initiates in animal caps. For the induction of Xnr3, VegT interacts negatively so as to inhibit the induction otherwise observed with wnt-signalling alone. The negative effect of VegT is not the result of a general inhibition of wnt-signalling, and does not result from an inhibition of wnt-induced siamois expression. A 294 bp proximal promoter fragment of the Xnr3 gene is sufficient to mediate the negative effect of VegT. Further experiments, employing cycloheximide to examine the dependence of Xnr gene expression upon proteins translated after the mid-blastula stage, demonstrated that Xnrs 4, 5 and 6 are 'primary' Xnr genes whose expression in the late blastula is solely dependent upon factors present before the mid-blastula stage.

Efficacy of protocols for induction of chronic hyperthyroidism in male and female mice.

PubMed

Engels, Kathrin; Rakov, Helena; Zwanziger, Denise; Hönes, Georg Sebastian; Rehders, Maren; Brix, Klaudia; Köhrle, Josef; Möller, Lars Christian; Führer, Dagmar

2016-10-01

Protocols for induction of hyperthyroidism in mice are highly variable and mostly involve short-term thyroid hormone (TH) treatment. In addition, little is known about a possible influence of sex on experimental TH manipulation. Here we analyzed the efficacy of intraperitoneal vs. oral levothyroxine (T4) administration to induce chronic hyperthyroidism in male and female mice and asked which T4 dosing intervals are required to achieve stable organ thyrotoxicosis. T4 was administered intraperitoneally or orally over a period of 6/7 weeks. Assessment included monitoring of body weight, TH serum concentrations, and serial quantitative TH target gene expression analysis in liver and heart. Our results show that both intraperitoneal and oral T4 treatment are reliable methods for induction of chronic hyperthyroidism in mice. Thereby T4 injection intervals should not exceed 48 h and oral levothyroxine should be administered continuously during experiments and up to sacrifice to ensure a hyperthyroid organ state. Furthermore, we found a sex-dependent variation in levothyroxine-induced TH serum state, with significantly higher T4 concentrations in female mice, while expression of investigated classical TH responsive genes in liver and heart did not vary with animal's sex. In summary, our study shows that common approaches for rendering rodents thyrotoxic can also be used for induction of chronic hyperthyroidism in male and female mice. Thereby T4 dosing intervals are critical as are read-out parameters to verify a chronic thyrotoxic organ state.

Streamed video clips to reduce anxiety in children during inhaled induction of anesthesia.

PubMed

Mifflin, Katherine A; Hackmann, Thomas; Chorney, Jill Maclaren

2012-11-01

Anesthesia induction in children is frequently achieved by inhalation of nitrous oxide and sevoflurane. Pediatric anesthesiologists commonly use distraction techniques such as humor or nonprocedural talk to reduce anxiety and facilitate a smooth transition at this critical phase. There is a large body of successful distraction research that explores the use of video and television distraction methods for minor medical and dental procedures, but little research on the use of this method for ambulatory surgery. In this randomized control trial study we examined whether video distraction is effective in reducing the anxiety of children undergoing inhaled induction before ambulatory surgery. Children (control = 47, video = 42) between 2 and 10 years old undergoing ambulatory surgery were randomly assigned to a video distraction or control group. In the video distraction group a video clip of the child's preference was played during induction, and the control group received traditional distraction methods during induction. The modified Yale Preoperative Anxiety Scale was used to assess the children's anxiety before and during the process of receiving inhalation anesthetics. All subjects were similar in their age and anxiety scores before entering the operating rooms. Children in the video distraction group were significantly less anxious at induction and showed a significantly smaller change in anxiety from holding to induction than did children in the control group. Playing video clips during the inhaled induction of children undergoing ambulatory surgery is an effective method of reducing anxiety. Therefore, pediatric anesthesiologists may consider using video distraction as a useful, valid, alternative strategy for achieving a smooth transition to the anesthetized state.

Clove oil as an anaesthetic for adult sockeye salmon: Field trials

USGS Publications Warehouse

Woody, C.A.; Nelson, Jack L.; Ramstad, K.

2002-01-01

Wild migrating sockeye salmon Oncorhynchus nerka exposed to 20, 50 and 80 mg 1-1 of clove oil could be handled within 3 min, recovered within 10 min, and survived 15 min exposure trials. Fish tested at 110 mg 1-1 did not recover from 15 min exposure trials. Response curves developed for induction and recovery time considered the following predictors: clove oil concentration, sex, fish length and depth. A significant positive dependence was observed between induction time and fish length for 20, 50 and 80 mg 1-1 test concentrations; no dependence was observed between induction time and length at 110 and 140 mg 1-1. Recovery time differed as a function of clove oil concentration, but not fish size. A concentration of 50 mg 1-1 is recommended for anaesthetizing sockeye salmon ranging in length from 400 to 550 mm at water temperatures averaging 9-10??C.

Growth phase-dependent induction of stationary-phase promoters of Escherichia coli in different gram-negative bacteria.

PubMed Central

Miksch, G; Dobrowolski, P

1995-01-01

RSF1010-derived plasmids carrying a fusion of a promoterless lacZ gene with the sigma s-dependent growth phase-regulated promoters of Escherichia coli, bolAp1 and fic, were constructed. The plasmids were mobilized into the gram-negative bacterial species Acetobacter methanolicus, Xanthomonas campestris, Pseudomonas putida, and Rhizobium meliloti. The beta-galactosidase activities of bacterial cultures were determined during exponential and stationary growth phases. Transcriptional activation of the fic promoter in the different bacteria was growth phase dependent as in E. coli and was initiated generally during the transition to stationary phase. The induction of the bolA promoter was also growth phase dependent in the bacteria tested. While the expression in E. coli and R. meliloti was initiated during the transition from exponential to stationary phase, the induction in A. methanolicus, P. putida, and X. campestris started some hours after stationary growth phase was reached. In all the species tested, DNA fragments hybridizing with the rpoS gene of E. coli were detected. The results show that in different gram-negative bacteria, stationary-phase-specific sigma factors which are structurally and functionally homologous to sigma s and are able to recognize the promoter sequences of both bolA and fic exist. PMID:7665531

The Effects of Brief and Elaborate Mood Induction Procedures on the Size of Young Children's Drawings

ERIC Educational Resources Information Center

Burkitt, E.; Barnett, N.

2006-01-01

It has been claimed that children's drawings following brief mood induction procedures differ in size depending on positive or negative mood. However there are conflicting findings in the field regarding the existence and direction of scaling changes. Such inconsistencies may be the result of methodological differences or may indicate that this…

Flexible heating head for induction heating apparatus and method

NASA Astrophysics Data System (ADS)

Coultrip, Robert H.; Copeland, Carl E.; Fox, Robert L.; Johnson, Samuel D., Jr.; Phillips, W. Morris; Buckley, John D.

1991-10-01

An induction heating head includes: a length of wire having first and second opposite ends and being wound in a flat spiral shape to form an induction coil; a capacitor connected to the first and second ends of the wire, the induction coil and capacitor defining a tank circuit; and a flexible, elastomeric body molded to encase the induction coil. When a susceptor is placed in juxtaposition to the body, and the tank circuit is powered, the susceptor is inductively heated.

Flexible heating head for induction heating apparatus and method

NASA Astrophysics Data System (ADS)

Fox, Robert L.; Johnson, Samuel D.; Coultrip, Robert H.; Phillips, W. Morris

1991-10-01

An induction heating head includes a length of wire having first and second opposite ends and being wound in a flat spiral shape to form an induction coil, a capacitor connected to the first and second ends of the wire, the induction coil and capacitor defining a tank circuit, and a flexible, elastomeric body molded to encase the induction coil. When a susceptor is placed in juxtaposition to the body, and the tank circuit is powered, the susceptor is inductively heated.

Method of processing materials using an inductively coupled plasma

DOEpatents

Hull, Donald E.; Bieniewski, Thomas M.

1989-01-01

A method for coating surfaces or implanting ions in an object using an inductively coupled plasma. The method provides a gas-free environment, since the plasma is formed without using a gas. The coating material or implantation material is intitially in solid form.

A Logic Programming Testbed for Inductive Thought and Specification.

ERIC Educational Resources Information Center

Neff, Norman D.

This paper describes applications of logic programming technology to the teaching of the inductive method in computer science and mathematics. It discusses the nature of inductive thought and its place in those fields of inquiry, arguing that a complete logic programming system for supporting inductive inference is not only feasible but necessary.…

Global electromagnetic induction in the moon and planets. [poloidal eddy current transient response

NASA Technical Reports Server (NTRS)

Dyal, P.; Parkin, C. W.

1973-01-01

Experiments and analyses concerning electromagnetic induction in the moon and other extraterrestrial bodies are summarized. The theory of classical electromagnetic induction in a sphere is first considered, and this treatment is extended to the case of the moon, where poloidal eddy-current response has been found experimentally to dominate other induction modes. Analysis of lunar poloidal induction yields lunar internal electrical conductivity and temperature profiles. Two poloidal-induction analytical techniques are discussed: a transient-response method applied to time-series magnetometer data, and a harmonic-analysis method applied to data numerically Fourier-transformed to the frequency domain, with emphasis on the former technique. Attention is given to complicating effects of the solar wind interaction with both induced poloidal fields and remanent steady fields. The static magnetization field induction mode is described, from which are calculated bulk magnetic permeability profiles. Magnetic field measurements obtained from the moon and from fly-bys of Venus and Mars are studied to determine the feasibility of extending theoretical and experimental induction techniques to other bodies in the solar system.

The role of c-Jun in controlling the EPAC1-dependent induction of the SOCS3 gene in HUVECs

PubMed Central

Wiejak, Jolanta; Dunlop, Julia; Yarwood, Stephen J.

2014-01-01

The cyclic AMP sensor, EPAC1, activates AP1-mediated transcription in HUVECs. Correspondingly, induction of the SOCS3 minimal promoter by EPAC1 requires a single AP1 site that constitutively binds phosphorylated (Ser63) c-Jun in DNA-pull-down assays. c-Jun (Ser63) becomes further phosphorylated following cyclic AMP stimulation and specific activation of protein kinase A (PKA), but not through selective activation of EPAC1. Moreover, despite a requirement for c-Jun for SOCS3 induction in fibroblasts, phospho-null c-Jun (Ser63/73Ala) had little effect on SOCS3 induction by cyclic AMP in HUVECs. AP1 activation and SOCS3 induction by EPAC1 in HUVECs therefore occur independently of c-Jun phosphorylation on Ser63. PMID:24631457

Interaction of exogenous refractory nanophases with antimony dissolved in liquid iron

NASA Astrophysics Data System (ADS)

Burtsev, V. T.; Anuchkin, S. N.; Samokhin, A. V.

2017-07-01

The heterophase interaction of Al2O3 refractory nanoparticles with a surfactant impurity (antimony) in the Fe-Sb (0.095 wt %)-O (0.008 wt %) system is studied. It is shown that the introduction of 0.06-0.18 wt % Al2O3 nanoparticles (25-83 nm) into a melt during isothermal holding for up to 1200 s leads to a decrease in the antimony content: the maximum degree of antimony removal is 26 rel %. The sessile drop method is used to investigate the surface tension and the density of Fe, Fe-Sb, and Fe-Sb-Al2O3 melts. The polytherms of the surface tension of these melts have a linear character, the removal of antimony from the Fe-Sb-Al2O3 melts depends on the time of melting in a vacuum induction furnace, and the experimental results obtained reveal the kinetic laws of the structure formation in the surface layers of the melts. The determined melt densities demonstrate that the introduction of antimony into the Fe-O melt causes an increase in its compression by 47 rel %. The structure of the Fe-Sb-O melt after the introduction of Al2O3 nanoparticles depends on the time of melting in a vacuum induction furnace.

Experimental analysis and simulation calculation of the inductances of loosely coupled transformer

NASA Astrophysics Data System (ADS)

Kerui, Chen; Yang, Han; Yan, Zhang; Nannan, Gao; Ying, Pei; Hongbo, Li; Pei, Li; Liangfeng, Guo

2017-11-01

The experimental design of iron-core wireless power transmission system is designed, and an experimental model of loosely coupled transformer is built. Measuring the air gap on both sides of the transformer 15mm inductor under the parameters. The feasibility and feasibility of using the finite element method to calculate the coil inductance parameters of the loosely coupled transformer are analyzed. The system was modeled by ANSYS, and the magnetic field was calculated by finite element method, and the inductance parameters were calculated. The finite element method is used to calculate the inductive parameters of the loosely coupled transformer, and the basis for the accurate compensation of the capacitance of the wireless power transmission system is established.

A quick and efficient method to generate mammalian stable cell lines based on a novel inducible alphavirus DNA/RNA layered system.

PubMed

Aranda, Alejandro; Bezunartea, Jaione; Casales, Erkuden; Rodriguez-Madoz, Juan R; Larrea, Esther; Prieto, Jesus; Smerdou, Cristian

2014-12-01

We report a new method to generate high-expressing mammalian cell lines in a quick and efficient way. For that purpose, we developed a master cell line (MCL) containing an inducible alphavirus vector expressing GFP integrated into the genome. In the MCL, recombinant RNA levels increased >4,600-fold after induction, due to a doxycycline-dependent RNA amplification loop. The MCL maintained inducibility and expression during 50 passages, being more efficient for protein expression than a conventional cell line. To generate new cell lines, mutant LoxP sites were inserted into the MCL, allowing transgene and selection gene exchange by Cre-directed recombination, leading to quick generation of inducible cell lines expressing proteins of therapeutic interest, like human cardiotrophin-1 and oncostatin-M at several mg/l/24 h. These proteins contained posttranslational modifications, showed bioactivity, and were efficiently purified. Remarkably, this system allowed production of toxic proteins, like oncostatin-M, since cells able to express it could be grown to the desired amount before induction. These cell lines were easily adapted to growth in suspension, making this methodology very attractive for therapeutic protein production.

High Resolution Switching Mode Inductance-to-Frequency Converter with Temperature Compensationti

PubMed Central

Matko, Vojko; Milanović, Miro

2014-01-01

This article proposes a novel method for the temperature-compensated inductance-to-frequency converter with a single quartz crystal oscillating in the switching oscillating circuit to achieve better temperature stability of the converter. The novelty of this method lies in the switching-mode converter, the use of additionally connected impedances in parallel to the shunt capacitances of the quartz crystal, and two inductances in series to the quartz crystal. This brings a considerable reduction of the temperature influence of AT-cut crystal frequency change in the temperature range between 10 and 40 °C. The oscillator switching method and the switching impedances connected to the quartz crystal do not only compensate for the crystal's natural temperature characteristics but also any other influences on the crystal such as ageing as well as from other oscillating circuit elements. In addition, the method also improves frequency sensitivity in inductance measurements. The experimental results show that through high temperature compensation improvement of the quartz crystal characteristics, this switching method theoretically enables a 2 pH resolution. It converts inductance to frequency in the range of 85–100 μH to 2–560 kHz. PMID:25325334

New Teacher Induction Programs: A Case Study of an Exemplary School District, and How It Prepares Its New Teachers for the Use of Instructional Technology in the Classroom

ERIC Educational Resources Information Center

Sherman, David B.

2014-01-01

This research study examined Generation Y new teachers, the process of new teacher induction, and the most effective methods for providing professional development in instructional technology for Generation Y teachers. This research study examined Generation Y new teachers, the process of new teacher induction, and the most effective methods for…

Differential effects on apoptosis induction in hepatocyte lines by stable expression of hepatitis B virus X protein

PubMed Central

Fiedler, Nicola; Quant, Ellen; Fink, Ludger; Sun, Jianguang; Schuster, Ralph; Gerlich, Wolfram H; Schaefer, Stephan

2006-01-01

AIM: Hepatitis B virus protein X (HBx) has been shown to be weakly oncogenic in vitro. The transforming activities of HBx have been linked with the inhibition of several functions of the tumor suppressor p53. We have studied whether HBx may have different effects on p53 depending on the cell type. METHODS: We used the human hepatoma cell line HepG2 and the immortalized murine hepatocyte line AML12 and analyzed stably transfected clones which expressed physiological amounts of HBx. P53 was induced by UV irradiation. RESULTS: The p53 induction by UV irradiation was unaffected by stable expression of HBx. However, the expression of the cyclin kinase inhibitor p21waf/cip/sdi which gets activated by p53 was affected in the HBx transformed cell line AML12-HBx9, but not in HepG2. In AML-HBx9 cells, p21waf/cip/sdi-protein expression and p21waf/cip/sdi transcription were deregulated. Furthermore, the process of apoptosis was affected in opposite ways in the two cell lines investigated. While stable expression of HBx enhanced apoptosis induced by UV irradiation in HepG2-cells, apoptosis was decreased in HBx transformed AML12-HBx9. P53 repressed transcription from the HBV enhancer I, when expressed from expression vectors or after induction of endogenous p53 by UV irradiation. Repression by endogenous p53 was partially reversible by stably expressed HBx in both cell lines. CONCLUSION: Stable expression of HBx leads to deregulation of apoptosis induced by UV irradiation depending on the cell line used. In an immortalized hepatocyte line HBx acted anti-apoptotic whereas expression in a carcinoma derived hepatocyte line HBx enhanced apoptosis. PMID:16937438

Induction of the high-affinity Na(+)-dependent glutamate transport system XAG- by hypertonic stress in the renal epithelial cell line NBL-1.

PubMed Central

Ferrer-Martinez, A; Felipe, A; Nicholson, B; Casado, J; Pastor-Anglada, M; McGivan, J

1995-01-01

The high-affinity Na(+)-dependent glutamate transport system XAG- is induced (threefold increase in Vmax. with no change in Km) by hypertonicity in the renal epithelial cell line NBL-1. This effect is dependent on protein synthesis and glycosylation and is accompanied by an increase in EAAC1 mRNA levels. Other Na(+)-dependent transport systems in this cell line do not respond to hypertonic stress. In contrast to recent findings [Ruiz-Montasell, Gomez-Angelats, Casado, Felipe, McGivan and Pastor-Anglada (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 9569-9573] showing that increased system A activity after hyperosmotic shock results from induction of a regulatory protein, this is the first demonstration that hypertonicity may increase the expression of the gene for an amino acid transport protein itself. Images Figure 4 PMID:7654212

Effect of different methods of pulse width modulation on power losses in an induction motor

NASA Astrophysics Data System (ADS)

Gulyaev, Alexander; Fokin, Dmitrii; Shuharev, Sergey; Ten, Evgenii

2017-10-01

We consider the calculation of modulation power losses in a system “induction motor-inverter” for various pulse width modulation (PWM) methods of the supply voltage. Presented values of modulation power losses are the result of modeling a system “DC link - two-level three-phase voltage inverter - induction motor - load”. In this study the power losses in a system “induction motor - inverter” are computed, as well as losses caused by higher harmonics of PWM supply voltage, followed by definition of active power consumed by the DC link for a specified value mechanical power on the induction motor shaft. Mechanical power was determined by the rotation speed and the torque on the motor shaft in various quasi-sinusoidal supply voltage PWM modes. These calculations reveal the best coefficient of performance (COP) in a system of a variable frequency drive (VFD) with independent voltage inverter controlled by induction motor PWM.

Localized mold heating with the aid of selective induction for injection molding of high aspect ratio micro-features

NASA Astrophysics Data System (ADS)

Park, Keun; Lee, Sang-Ik

2010-03-01

High-frequency induction is an efficient, non-contact means of heating the surface of an injection mold through electromagnetic induction. Because the procedure allows for the rapid heating and cooling of mold surfaces, it has been recently applied to the injection molding of thin-walled parts or micro/nano-structures. The present study proposes a localized heating method involving the selective use of mold materials to enhance the heating efficiency of high-frequency induction heating. For localized induction heating, a composite injection mold of ferromagnetic material and paramagnetic material is used. The feasibility of the proposed heating method is investigated through numerical analyses in terms of its heating efficiency for localized mold surfaces and in terms of the structural safety of the composite mold. The moldability of high aspect ratio micro-features is then experimentally compared under a variety of induction heating conditions.

Inductive High Power Transfer Technologies for Electric Vehicles

NASA Astrophysics Data System (ADS)

Madzharov, Nikolay D.; Tonchev, Anton T.

2014-03-01

Problems associated with "how to charge the battery pack of the electric vehicle" become more important every passing day. Most logical solution currently is the non-contact method of charge, possessing a number of advantages over standard contact methods for charging. This article focuses on methods for Inductive high power contact-less transfer of energy at relatively small distances, their advantages and disadvantages. Described is a developed Inductive Power Transfer (IPT) system for fast charging of electric vehicles with nominal power of 30 kW over 7 to 9 cm air gap.

Inductive System for Reliable Magnesium Level Detection in a Titanium Reduction Reactor

NASA Astrophysics Data System (ADS)

Krauter, Nico; Eckert, Sven; Gundrum, Thomas; Stefani, Frank; Wondrak, Thomas; Frick, Peter; Khalilov, Ruslan; Teimurazov, Andrei

2018-05-01

The determination of the Magnesium level in a Titanium reduction retort by inductive methods is often hampered by the formation of Titanium sponge rings which disturb the propagation of electromagnetic signals between excitation and receiver coils. We present a new method for the reliable identification of the Magnesium level which explicitly takes into account the presence of sponge rings with unknown geometry and conductivity. The inverse problem is solved by a look-up-table method, based on the solution of the inductive forward problems for several tens of thousands parameter combinations.

Dendritic small conductance calcium-activated potassium channels activated by action potentials suppress EPSPs and gate spike-timing dependent synaptic plasticity.

PubMed

Jones, Scott L; To, Minh-Son; Stuart, Greg J

2017-10-23

Small conductance calcium-activated potassium channels (SK channels) are present in spines and can be activated by backpropagating action potentials (APs). This suggests they may play a critical role in spike-timing dependent synaptic plasticity (STDP). Consistent with this idea, EPSPs in both cortical and hippocampal pyramidal neurons were suppressed by preceding APs in an SK-dependent manner. In cortical pyramidal neurons EPSP suppression by preceding APs depended on their precise timing as well as the distance of activated synapses from the soma, was dendritic in origin, and involved SK-dependent suppression of NMDA receptor activation. As a result SK channel activation by backpropagating APs gated STDP induction during low-frequency AP-EPSP pairing, with both LTP and LTD absent under control conditions but present after SK channel block. These findings indicate that activation of SK channels in spines by backpropagating APs plays a key role in regulating both EPSP amplitude and STDP induction.

Differential suppression of glial nitric oxide synthase induction by structurally related tyrosine kinase inhibitors.

PubMed

Galea, E; Reddi, J; Feinstein, D L

1995-11-24

Incubation of C6 astrocytoma cells with bacterial endotoxin (lipopolysaccharide; LPS) plus interferon-gamma (IFN-gamma), or with a combination of cytokines (TNF-alpha, IL1-beta, and IFN-gamma) leads to high levels of inducible nitric oxide synthase (iNOS) expression. Previous results demonstrated a requirement for tyrosine kinase (TK) activities for iNOS induction. In the present study, a set of structurally related TK inhibitors, the tyrphostins (TYRs), were used to characterize possible differences between LPS and cytokine iNOS induction. All TYRs tested suppressed both types of induction. However, dose-response curves revealed significant differences in the IC50 values obtained for some TYRs (T25 and T56), and significant differences in the IC50 potency rank order when comparing inhibition of LPS versus cytokine-dependent iNOS induction. These results are consistent with differential TK utilization by the LPS versus cytokine pathways of iNOS induction, and establish a basis for developing further selective inhibitors of iNOS expression.

DNA double strand break induction in yeast.

PubMed

Kiefer, J; Egenolf, R; Ikpeme, S E

2002-01-01

The induction of DNA double strand breaks (DSBs) by accelerated heavy ions was systematically measured in diploid yeast cells. Particles were provided by the accelerators at GSI, Darmstadt, and HMI, Berlin. DNA was separated using pulsed field gel electrophoresis and the intensity of the largest bands used to determine the loss of molecular weight. Since the DNA content of each chromosome is exactly known absolute values for DSB induction can be measured without calibration procedures. Ions used range from protons to uranium with LET values between 2 and about 15,000 keV.micron-1. Induction cross sections increase in the lower LET region approaching a plateau around 200 keV.micron-1. With higher LET values the dependence can no longer be described by a common curve with each ion showing a specific behaviour. With very heavy particles the influence of the penumbra becomes obvious: cross sections decrease with LET because of the reduced penumbra extensions. Classical target theory would predict cross sections to follow a simple saturation function which is not substantiated by the data. Track structure analysis as introduced by Butts and Katz in 1967 is also not able to predict the experimental results. A semi-empirical fit indicates a linear-quadratic dependence of induction cross sections on LET up to about 1000 keV.micron-1. RBE for DSB induction rises above unity reaching a maximum of about 2.5 around 200 keV.micron-1. This is different from many experiments in mammalian cells and is presumably due to differences in chromatin structure since yeast cells seem to lack a functional III histone.

Antiproliferative Activity and Apoptosis Inducing Mechanism of Anthocephalus cadamba on Dalton’s Lymphoma Ascites Cells

PubMed Central

Dolai, Narayan; Islam, Aminul; Haldar, Pallab Kanti

2016-01-01

The purpose of this investigation was to evaluate the antiproliferative and apoptogenic mechanistic studies of methanol extract of Anthocephalus cadamba (MEAC) on Dalton’s lymphoma ascites (DLA) cells treated mice. Determination of antiproliferative activity was performed by using different DLA cells (2×106 cells, i.p.) inoculated mice groups (n = 12). Groups were treated for 14 consecutive days with MEAC at the doses of 200 and 400 mg/Kg b.w. respectively. The mechanism of antiproliferation activity of MEAC was investigated through morphological studies by acridine orange (AO)/ethidium bromide (EB) double staining method. Comet assay was estimated to check the DNA damage induced apoptosis property. Furthermore, flow cytometry (FACS) was used to quantitatively detect the apoptotic rate by double labeling techniques using Annexin-V FITC/propidium iodide staining analysis and apoptotic proteins expression done by western blotting assay method. MEAC exhibited significant (p<0.01) decrease the tumor volume, viable cell count, tumor weight and elevated the life span of DLA tumor bearing mice. Analysis of AO/EB staining and flow cytometry showed that MEAC possessed apoptosis induced antitumor activity on DLA cells in a dose dependant manner. Dose dependent induction of DNA damage on DLA cells were observed after MEAC treatment, which was evident from the appearance of comet tail length. Pro-apoptotic gene, Bax was up-regulated and down-regulation of the Bcl-2/Bax ratio, suggesting that Bcl-2 family involved in the control of apoptosis. Experimental results revealed that MEAC possess potent antitumor activity via induction of cancer cell apoptosis mechanism. PMID:27980586

Efficient Power Network Analysis with Modeling of Inductive Effects

NASA Astrophysics Data System (ADS)

Zeng, Shan; Yu, Wenjian; Hong, Xianlong; Cheng, Chung-Kuan

In this paper, an efficient method is proposed to accurately analyze large-scale power/ground (P/G) networks, where inductive parasitics are modeled with the partial reluctance. The method is based on frequency-domain circuit analysis and the technique of vector fitting [14], and obtains the time-domain voltage response at given P/G nodes. The frequency-domain circuit equation including partial reluctances is derived, and then solved with the GMRES algorithm with rescaling, preconditioning and recycling techniques. With the merit of sparsified reluctance matrix and iterative solving techniques for the frequency-domain circuit equations, the proposed method is able to handle large-scale P/G networks with complete inductive modeling. Numerical results show that the proposed method is orders of magnitude faster than HSPICE, several times faster than INDUCTWISE [4], and capable of handling the inductive P/G structures with more than 100, 000 wire segments.

Roles of p62 in BDNF-dependent autophagy suppression and neuroprotection against mitochondrial dysfunction in rat cortical neurons.

PubMed

Wu, Chia-Lin; Chen, Chien-Hui; Hwang, Chi-Shin; Chen, Shang-Der; Hwang, Wei-Chao; Yang, Ding-I

2017-03-01

Previously, we have reported that pre-conditioning of primary rat cortical neurons with brain-derived neurotrophic factor (BDNF) may exert neuroprotective effects against 3-nitropropionic acid (3-NP), a mitochondrial complex II inhibitor. However, the underlying mechanisms, especially potential involvements of autophagy, remain elusive. In this work, we tested the hypothesis that BDNF may suppress 3-NP-induced autophagy to exert its neuroprotective effects by inducing the expression of p62/sequestosome-1 in primary cortical neurons. We found that 3-NP increased total level of microtubule-associated protein 1A/1B-light chain (LC)-3 as well as the LC3-II/LC3-I ratio, an index of autophagy, in primary cortical neurons. BDNF decreased LC3-II/LC3-I ratio and time-dependently induced expression of p62. Knockdown of p62 by siRNA restored LC3-II/LC3-I ratio and increased total LC3 levels associated with BDNF exposure; p62 knockdown also abolished BDNF-dependent neuroprotection against 3-NP. Upstream of p62, we found that BDNF triggered phosphorylation of mammalian target of rapamycin (mTOR) and its downstream mediator p70S6K; importantly, the mTOR inhibitor rapamycin reduced both BDNF-dependent p62 induction as well as 3-NP resistance. BDNF is known to induce c-Jun in cortical neurons. We found that c-Jun knockdown in part attenuated BDNF-mediated p62 induction, whereas p62 knockdown had no significant effects on c-Jun expression. In addition to suppressing p62 induction, rapamycin also partially suppressed BDNF-induced c-Jun expression, but c-Jun knockdown failed to affect mTOR activation. Together, our results suggested that BDNF inhibits 3-NP-induced autophagy via, at least in part, mTOR/c-Jun-dependent induction of p62 expression, together contributing to neuroprotection against mitochondrial inhibition. © 2016 International Society for Neurochemistry.

Correlation between tunability and anisotropy in magnetoelectric voltage tunable inductor (VTI).

PubMed

Yan, Yongke; Geng, Liwei D; Zhang, Lujie; Gao, Xiangyu; Gollapudi, Sreenivasulu; Song, Hyun-Cheol; Dong, Shuxiang; Sanghadasa, Mohan; Ngo, Khai; Wang, Yu U; Priya, Shashank

2017-11-22

Electric field modulation of magnetic properties via magnetoelectric coupling in composite materials is of fundamental and technological importance for realizing tunable energy efficient electronics. Here we provide foundational analysis on magnetoelectric voltage tunable inductor (VTI) that exhibits extremely large inductance tunability of up to 1150% under moderate electric fields. This field dependence of inductance arises from the change of permeability, which correlates with the stress dependence of magnetic anisotropy. Through combination of analytical models that were validated by experimental results, comprehensive understanding of various anisotropies on the tunability of VTI is provided. Results indicate that inclusion of magnetic materials with low magnetocrystalline anisotropy is one of the most effective ways to achieve high VTI tunability. This study opens pathway towards design of tunable circuit components that exhibit field-dependent electronic behavior.

Line transients with corona

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

Saied, M.M.; Safar, Y.A.; Salama, M.H.

1987-01-01

This paper investigates the effect of corona on the electromagnetic transients along high voltage overhead lines. A method is presented to simulate the line by dividing it into a number of sections connected in cascade. For {ital n} line sections, the number of the unknown variables is 2{ital n} + 1. The method allows any waveform of the exciting voltage function, as well as any impedance loading condition. The corona is represented by voltage-dependent shunt current sources. A systematic way for writing a sufficient number of differential equations is shown. For their solution, a digital computer subroutine based on themore » Runge--Kutta--Verner method was used. An artificial frequency-dependent damping by means of linear resistors was used to suppress the Gibb's oscillations in the solution. The proposed method is applied to study the transients on a 40 km high voltage line with 30-ft flat phase spacing and a single 1.4 inch ACSR conductor per phase. The exciting voltage has a double-exponential impulse waveform. Solutions are given for three values of resistive loads Z{sub {ital c}}2Z{sub {ital c}} and Z{sub {ital c}}/2, where Z{sub {ital c}} is the line surge impedance. The results of two interesting cases of inductive and capacitive loads are also given. Physical interpretations for the different solutions are given. Also, the current-voltage duality between inductive and capacitive loads is recognized. The corona was found to attenuate and distort the travelling waves. For example, during one wave excursion, the reduction of the current wave peaks can reach values as high as 8.5%. The effect is more noticeable in the current than in the voltage waves. As expected, it increases also with the line corona losses. The effect of the increase of the line effective capacitance due to the corona discharge is also demonstrated.« less

Automated identification of protein-ligand interaction features using Inductive Logic Programming: a hexose binding case study.

PubMed

A Santos, Jose C; Nassif, Houssam; Page, David; Muggleton, Stephen H; E Sternberg, Michael J

2012-07-11

There is a need for automated methods to learn general features of the interactions of a ligand class with its diverse set of protein receptors. An appropriate machine learning approach is Inductive Logic Programming (ILP), which automatically generates comprehensible rules in addition to prediction. The development of ILP systems which can learn rules of the complexity required for studies on protein structure remains a challenge. In this work we use a new ILP system, ProGolem, and demonstrate its performance on learning features of hexose-protein interactions. The rules induced by ProGolem detect interactions mediated by aromatics and by planar-polar residues, in addition to less common features such as the aromatic sandwich. The rules also reveal a previously unreported dependency for residues cys and leu. They also specify interactions involving aromatic and hydrogen bonding residues. This paper shows that Inductive Logic Programming implemented in ProGolem can derive rules giving structural features of protein/ligand interactions. Several of these rules are consistent with descriptions in the literature. In addition to confirming literature results, ProGolem's model has a 10-fold cross-validated predictive accuracy that is superior, at the 95% confidence level, to another ILP system previously used to study protein/hexose interactions and is comparable with state-of-the-art statistical learners.

Understanding Artifacts in Impedance Spectroscopy

DOE PAGES

Veal, B. W.; Baldo, P. M.; Paulikas, A. P.; ...

2014-11-22

Four-terminal measurements of impedance spectra have long been troubled by the presence of high frequency artifacts that typically indicate unphysically large inductive behavior. In this paper, we follow up on the observation of Fleig et al., that voltage and current are necessarily measured in different locations of the potentiostat circuit, and that, typically, the electrometer input is a virtual ground. In this case, the capacitance of coaxial cables that connect sample electrodes to the potentiostat provides a high frequency conduction path to ground, so that some of the current that passes through the sample bypasses the electrometer. In four-electrode measurements,more » this mechanism produces the observed inductive artifacts. We examine a variety of simulated samples, with calculations compared to measurements of relevant circuits, to quantitatively investigate the nature of the artifacts. Model results agree with measurements when the leakage capacitances are properly included in the circuit analyses. With understanding of the origin of the inductive artifacts, the four-electrode method can be effectively utilized, enabling a combination of two-, three- and four-electrode measurements to be used to best advantage. Finally, using this combination of electrode configurations, temperature dependent measurements of SrTiO 3, Y 2O 3-stabilized ZrO 2, and In 2O 3 films deposited on YSZ substrates are presented.« less

Contact-dependent depletion of hydrogen peroxide by catalase is a novel mechanism of myeloid-derived suppressor cell induction operating in human hepatic stellate cells.

PubMed

Resheq, Yazid J; Li, Ka-Kit; Ward, Stephen T; Wilhelm, Annika; Garg, Abhilok; Curbishley, Stuart M; Blahova, Miroslava; Zimmermann, Henning W; Jitschin, Regina; Mougiakakos, Dimitrios; Mackensen, Andreas; Weston, Chris J; Adams, David H

2015-03-15

Myeloid-derived suppressor cells (MDSC) represent a unique cell population with distinct immunosuppressive properties that have been demonstrated to shape the outcome of malignant diseases. Recently, human hepatic stellate cells (HSC) have been reported to induce monocytic-MDSC from mature CD14(+) monocytes in a contact-dependent manner. We now report a novel and unexpected mechanism by which CD14(+)HLADR(low/-) suppressive cells are induced by catalase-mediated depletion of hydrogen peroxide (H2O2). Incubation of CD14(+) monocytes with catalase led to a significant induction of functional MDSC compared with media alone, and H2O2 levels inversely correlated with MDSC frequency (r = -0.6555, p < 0.05). Catalase was detected in primary HSC and a stromal cell line, and addition of the competitive catalase inhibitor hydroxylamine resulted in a dose-dependent impairment of MDSC induction and concomitant increase of H2O2 levels. The NADPH-oxidase subunit gp91 was significantly increased in catalase-induced MDSC as determined by quantitative PCR outlining the importance of oxidative burst for the induction of MDSC. These findings represent a so far unrecognized link between immunosuppression by MDSC and metabolism. Moreover, this mechanism potentially explains how stromal cells can induce a favorable immunological microenvironment in the context of tissue oxidative stress such as occurs during cancer therapy. Copyright © 2015 by The American Association of Immunologists, Inc.

A beta1-adrenergic receptor CaM kinase II-dependent pathway mediates cardiac myocyte fetal gene induction.

PubMed

Sucharov, Carmen C; Mariner, Peter D; Nunley, Karin R; Long, Carlin; Leinwand, Leslie; Bristow, Michael R

2006-09-01

Beta-adrenergic signaling plays an important role in the natural history of dilated cardiomyopathies. Chronic activation of beta-adrenergic receptors (beta1-AR and beta2-AR) during periods of cardiac stress ultimately harms the failing heart by mechanisms that include alterations in gene expression. Here, we show that stimulation of beta-ARs with isoproterenol in neonate rat ventricular myocytes causes a "fetal" response in the relative activities of the human cardiac fetal and/or adult gene promoters that includes repression of the human and rat alpha-myosin heavy chain (alpha-MyHC) promoters with simultaneous activation of the human atrial natriuretic peptide (ANP) and rat beta-MyHC promoters. We also show that the promoter changes correlate with changes in endogenous gene expression as measured by mRNA expression. Furthermore, we show that these changes are specifically mediated by the beta1-AR, but not the beta2-AR, and are independent of alpha1-AR stimulation. We also demonstrate that the fetal gene response is independent of cAMP and protein kinase A, whereas inhibition of Ca2+/calmodulin-dependent protein kinase (CaMK) pathway blocks isoproterenol-mediated fetal gene program induction. Finally, we show that induction of the fetal program is dependent on activation of the L-type Ca2+ channel. We conclude that in neonatal rat cardiac myocytes, agonist-occupied beta1-AR mobilizes Ca2+ stores to activate fetal gene induction through cAMP independent pathways that involve CaMK.

Adaptation of Candida albicans to Reactive Sulfur Species

PubMed Central

Chebaro, Yasmin; Lorenz, Michael; Fa, Alice; Zheng, Rui; Gustin, Michael

2017-01-01

Candida albicans is an opportunistic fungal pathogen that is highly resistant to different oxidative stresses. How reactive sulfur species (RSS) such as sulfite regulate gene expression and the role of the transcription factor Zcf2 and the sulfite exporter Ssu1 in such responses are not known. Here, we show that C. albicans specifically adapts to sulfite stress and that Zcf2 is required for that response as well as induction of genes predicted to remove sulfite from cells and to increase the intracellular amount of a subset of nitrogen metabolites. Analysis of mutants in the sulfate assimilation pathway show that sulfite conversion to sulfide accounts for part of sulfite toxicity and that Zcf2-dependent expression of the SSU1 sulfite exporter is induced by both sulfite and sulfide. Mutations in the SSU1 promoter that selectively inhibit induction by the reactive nitrogen species (RNS) nitrite, a previously reported activator of SSU1, support a model for C. albicans in which Cta4-dependent RNS induction and Zcf2-dependent RSS induction are mediated by parallel pathways, different from S. cerevisiae in which the transcription factor Fzf1 mediates responses to both RNS and RSS. Lastly, we found that endogenous sulfite production leads to an increase in resistance to exogenously added sulfite. These results demonstrate that C. albicans has a unique response to sulfite that differs from the general oxidative stress response, and that adaptation to internal and external sulfite is largely mediated by one transcription factor and one effector gene. PMID:28235888

Outpatient versus inpatient induction of labour for improving birth outcomes.

PubMed

Kelly, Anthony J; Alfirevic, Zarko; Ghosh, Arpita

2013-11-12

More than 20% of women undergo induction of labour in some countries. The different methods used to induce labour have been the focus of previous reviews, but the setting in which induction takes place (hospital versus outpatient settings) may have implications for maternal satisfaction and costs. It is not known whether some methods of induction that are effective and safe in hospital are suitable in outpatient settings. To assess the effects on outcomes for mothers and babies of induction of labour for women managed as outpatients versus inpatients. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 June 2013). Published and unpublished randomised and quasi-randomised trials in which inpatient and outpatient methods of cervical ripening or induction of labour have been compared. Two review authors independently assessed trial reports for inclusion. Two review authors carried out data extraction and assessment of risk of bias independently. We included four trials, with a combined total of 1439 women in the review; each trial examined a different method of induction and we were unable to pool the results from trials.1. Vaginal PGE2 (two studies including 1028 women). There were no differences between women managed as outpatients versus inpatients for most review outcomes. There was no evidence of a difference between the likelihood of women requiring instrumental delivery in either setting (risk ratio (RR) 1.29; 95% confidence interval (CI) 0.79 to 2.13). The overall length of hospital stay was similar in the two groups.2. Controlled release PGE2 10 mg (one study including 300 women). There was no evidence of differences between groups for most review outcomes, including success of induction. During the induction period itself, women in the outpatient group were more likely to report high levels of satisfaction with their care (satisfaction rated seven or more on a nine-point scale, RR 1.42; 95% CI 1.11 to 1.81), but satisfaction scores measured postnatally were similar in the two groups.3. Foley catheter (one study including 111 women). There was no evidence of differences between groups for caesarean section rates, total induction time and the numbers of babies admitted to neonatal intensive care. The data available to evaluate the efficacy or potential hazards of outpatient induction are limited. It is, therefore, not yet possible to determine whether induction of labour is effective and safe in outpatient settings.

Outpatient versus inpatient induction of labour for improving birth outcomes.

PubMed

Kelly, Anthony J; Alfirevic, Zarko; Dowswell, Therese

2009-04-15

More than 20% of women undergo induction of labour in some countries. The different methods used to induce labour have been the focus of previous reviews, but the setting in which induction takes place (hospital versus outpatient settings) may have implications for maternal satisfaction and costs. It is not known whether some methods of induction that are effective and safe in hospital are suitable in outpatient settings. To assess the effects on outcomes for mothers and babies of induction of labour for women managed as outpatients versus inpatients. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (December 2008). Published and unpublished randomised and quasi-randomised trials in which inpatient and outpatient methods of cervical ripening or induction of labour have been compared. Two review authors independently assessed trial reports for inclusion. Two review authors carried out data extraction and assessment of risk of bias independently. We included three trials, with a combined total of 612 women in the review; each examined a different method of induction and we were unable to pool the results from trials.1. Vaginal PGE2 (One study including 201 women). There were no differences between women managed as out- versus inpatients for most review outcomes. Women in the outpatient group were more likely to have instrumental deliveries (risk ratio (RR) 1.74; 95% confidence interval (CI) 1.03 to 2.93). The overall length of hospital stay was similar in the two groups.2. Controlled release PGE2 10mg (one study including 300 women). There was no evidence of differences between groups for most review outcomes, including success of induction. During the induction period itself, women in the outpatient group were more likely to report high levels of satisfaction with their care (satisfaction rated seven or more on a nine-point scale RR 1.42; 95% CI 1.11 to 1.81), but satisfaction scores measured postnatally were similar in the two groups.3. Foley catheter (one study including 111 women). There was no evidence of differences between groups for caesarean section rates, total induction time and the numbers of babies admitted to neonatal intensive care. The data available to evaluate the efficacy or potential hazards of outpatient induction are limited. It is, therefore, not yet possible to determine whether induction of labour is effective and safe in outpatient settings.

Simulations towards the achievement of non-inductive current ramp-up and sustainment in the National Spherical Torus Experiment Upgrade

DOE PAGES

Poli, F. M.; Andre, R. G.; Bertelli, N.; ...

2015-10-30

One of the goals of the National Spherical Torus Experiment Upgrade (NSTX-U) (Menard et al 2012 Nucl. Fusion 52 083015) is the demonstration of fully non-inductive start-up, current ramp-up and sustainment. This work discusses predictive simulations where the available heating and current drive systems are combined to maximize the non-inductive current and minimize the solenoidal contribution. Radio-frequency waves at harmonics higher than the ion cyclotron resonance (high-harmonic fast waves (HHFW)) and neutral beam injection are used to ramp the plasma current non-inductively starting from an initial Ohmic plasma. An interesting synergy is observed in the simulations between the HHFW andmore » electron cyclotron (EC) wave heating. Furthermore, time-dependent simulations indicate that, depending on the phasing of the HHFW antenna, EC wave heating can significantly increase the effectiveness of the radio-frequency power, by heating the electrons and increasing the current drive efficiency, thus relaxing the requirements on the level of HHFW power that needs to be absorbed in the core plasma to drive the same amount of fast-wave current.« less

Role of protein kinase C in the induction and maintenance of serotonin-dependent enhancement of the glutamate response in isolated siphon motor neurons of Aplysia californica.

PubMed

Villareal, Greg; Li, Quan; Cai, Diancai; Fink, Ann E; Lim, Travis; Bougie, Joanna K; Sossin, Wayne S; Glanzman, David L

2009-04-22

Serotonin (5-HT) mediates learning-related facilitation of sensorimotor synapses in Aplysia californica. Under some circumstances 5-HT-dependent facilitation requires the activity of protein kinase C (PKC). One critical site of PKC's contribution to 5-HT-dependent synaptic facilitation is the presynaptic sensory neuron. Here, we provide evidence that postsynaptic PKC also contributes to synaptic facilitation. We investigated the contribution of PKC to enhancement of the glutamate-evoked potential (Glu-EP) in isolated siphon motor neurons in cell culture. A 10 min application of either 5-HT or phorbol ester, which activates PKC, produced persistent (> 50 min) enhancement of the Glu-EP. Chelerythrine and bisindolylmaleimide-1 (Bis), two inhibitors of PKC, both blocked the induction of 5-HT-dependent enhancement. An inhibitor of calpain, a calcium-dependent protease, also blocked 5-HT's effect. Interestingly, whereas chelerythrine blocked maintenance of the enhancement, Bis did not. Because Bis has greater selectivity for conventional and novel isoforms of PKC than for atypical isoforms, this result implicates an atypical isoform in the maintenance of 5-HT's effect. Although induction of enhancement of the Glu-EP requires protein synthesis (Villareal et al., 2007), we found that maintenance of the enhancement does not. Maintenance of 5-HT-dependent enhancement appears to be mediated by a PKM-type fragment generated by calpain-dependent proteolysis of atypical PKC. Together, our results suggest that 5-HT treatment triggers two phases of PKC activity within the motor neuron, an early phase that may involve conventional, novel or atypical isoforms of PKC, and a later phase that selectively involves an atypical isoform.

The external amino acid signaling pathway promotes activation of Stp1 and Uga35/Dal81 transcription factors for induction of the AGP1 gene in Saccharomyces cerevisiae.

PubMed Central

Abdel-Sater, Fadi; Iraqui, Ismaïl; Urrestarazu, Antonio; André, Bruno

2004-01-01

Yeast cells respond to the presence of amino acids in their environment by inducing transcription of several amino acid permease genes including AGP1, BAP2, and BAP3. The signaling pathway responsible for this induction involves Ssy1, a permease-like sensor of external amino acids, and culminates with proteolytic cleavage and translocation to the nucleus of the zinc-finger proteins Stp1 and Stp2, the lack of which abolishes induction of BAP2 and BAP3. Here we show that Stp1-but not Stp2-plays an important role in AGP1 induction, although significant induction of AGP1 by amino acids persists in stp1 and stp1 stp2 mutants. This residual induction depends on the Uga35/Dal81 transcription factor, indicating that the external amino acid signaling pathway activates not only Stp1 and Stp2, but also another Uga35/Dal81-dependent transcriptional circuit. Analysis of the AGP1 gene's upstream region revealed that Stp1 and Uga35/Dal81 act synergistically through a 21-bp cis-acting sequence similar to the UAS(AA) element previously found in the BAP2 and BAP3 upstream regions. Although cells growing under poor nitrogen-supply conditions display much higher induction of AGP1 expression than cells growing under good nitrogen-supply conditions, the UAS(AA) itself is totally insensitive to nitrogen availability. Nitrogen-source control of AGP1 induction is mediated by the GATA factor Gln3, likely acting through adjacent 5'-GATA-3' sequences, to amplify the positive effect of UAS(AA). Our data indicate that Stp1 may act in combination with distinct sets of transcription factors, according to the gene context, to promote induction of transcription in response to external amino acids. The data also suggest that Uga35/Dal81 is yet another transcription factor under the control of the external amino acid sensing pathway. Finally, the data show that the TOR pathway mediating global nitrogen control of transcription does not interfere with the external amino acid signaling pathway. PMID:15126393

Dual regulation of skin sensitizer-induced HMOX1 expression by Bach1 and Nrf2: Comparison to regulation of the AKR1C2-ARE element in the KeratinoSens cell line

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

Emter, Roger; Natsch, Andreas, E-mail: andreas.natsch@givaudan.com

2015-11-01

Heme oxygenase (decycling) 1 (HMOX1) is the most consistently found genetic marker induced by skin sensitizers. HMOX1 is often referred to as typical gene regulated by nuclear factor erythroid 2-related factor 2 (Nrf2), however, it is also regulated by other DNA-binding factors, including BTB and CNC homolog 1 (Bach1). The KeratinoSens™ assay is the first validated in vitro assay for sensitizers that measures gene induction. It is based on luciferase expression regulated by the antioxidant response element (ARE) of the aldoketoreductase 1C2 (AKR1C2) gene. Luciferase upregulation is dependent on Nrf2, while HMOX1 upregulation is only partially Nrf2-dependent. Thus, sensitizer-dependent activationmore » of HMOX1 may integrate multiple signals thereby providing additional information. We constructed reporter cell lines containing the full HMOX1 regulatory region or the HMOX1-ARE sequence and compared them with the construct containing the AKR1C2-ARE sequence. Induction of the AKR1C2-ARE depends on Nrf2, but not on the repressor Bach1. Results obtained with HMOX1-ARE and the full HMOX1 promoter indicate that, within the HMOX1 promoter, the HMOX1-ARE is sufficient to explain the induction by sensitizers and that (i) inhibiting Bach1 leads to strong basal expression, (ii) fold-induction by sensitizers above this level is reduced in the absence of Bach1 and (iii) these constructs are less dependent on Nrf2 as compared to the AKR1C2-ARE. Nevertheless, congruent dose response curves for luciferase activity were obtained with all constructs. Thus, while sensitizer-induced HMOX1 activation is dependent on Nrf2 and Bach1, all constructs give identical information for the in vitro prediction of the sensitization potential. - Highlights: • HMOX1 is a key genetic marker up-regulated by skin sensitizers. • HMOX1-, but not AKR1C2-upregulation, is dependent on both Nrf2 and Bach1. • AKR1C2 and HMOX1-dependent reporter constructs yield congruent dose response curves. • Combining both constructs offers no advantage over either construct used alone.« less

Feedback control design for non-inductively sustained scenarios in NSTX-U using TRANSP

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

Boyer, M. D.; Andre, R. G.; Gates, D. A.

This paper examines a method for real-time control of non-inductively sustained scenarios in NSTX-U by using TRANSP, a time-dependent integrated modeling code for prediction and interpretive analysis of tokamak experimental data, as a simulator. The actuators considered for control in this work are the six neutral beam sources and the plasma boundary shape. To understand the response of the plasma current, stored energy, and central safety factor to these actuators and to enable systematic design of control algorithms, simulations were run in which the actuators were modulated and a linearized dynamic response model was generated. A multi-variable model-based control schememore » that accounts for the coupling and slow dynamics of the system while mitigating the effect of actuator limitations was designed and simulated. Simulations show that modest changes in the outer gap and heating power can improve the response time of the system, reject perturbations, and track target values of the controlled values.« less

Feedback control design for non-inductively sustained scenarios in NSTX-U using TRANSP

DOE PAGES

Boyer, M. D.; Andre, R. G.; Gates, D. A.; ...

2017-04-24

This paper examines a method for real-time control of non-inductively sustained scenarios in NSTX-U by using TRANSP, a time-dependent integrated modeling code for prediction and interpretive analysis of tokamak experimental data, as a simulator. The actuators considered for control in this work are the six neutral beam sources and the plasma boundary shape. To understand the response of the plasma current, stored energy, and central safety factor to these actuators and to enable systematic design of control algorithms, simulations were run in which the actuators were modulated and a linearized dynamic response model was generated. A multi-variable model-based control schememore » that accounts for the coupling and slow dynamics of the system while mitigating the effect of actuator limitations was designed and simulated. Simulations show that modest changes in the outer gap and heating power can improve the response time of the system, reject perturbations, and track target values of the controlled values.« less

Feedback control design for non-inductively sustained scenarios in NSTX-U using TRANSP

NASA Astrophysics Data System (ADS)

Boyer, M. D.; Andre, R. G.; Gates, D. A.; Gerhardt, S. P.; Menard, J. E.; Poli, F. M.

2017-06-01

This paper examines a method for real-time control of non-inductively sustained scenarios in NSTX-U by using TRANSP, a time-dependent integrated modeling code for prediction and interpretive analysis of tokamak experimental data, as a simulator. The actuators considered for control in this work are the six neutral beam sources and the plasma boundary shape. To understand the response of the plasma current, stored energy, and central safety factor to these actuators and to enable systematic design of control algorithms, simulations were run in which the actuators were modulated and a linearized dynamic response model was generated. A multi-variable model-based control scheme that accounts for the coupling and slow dynamics of the system while mitigating the effect of actuator limitations was designed and simulated. Simulations show that modest changes in the outer gap and heating power can improve the response time of the system, reject perturbations, and track target values of the controlled values.

Apoptogenic effects of β-sitosterol glucoside from Castanopsis indica leaves.

PubMed

Dolai, Narayan; Kumar, Ashish; Islam, Aminul; Haldar, Pallab K

2016-01-01

β-Sitosterol glucoside (BSSG) is a natural biologically active substance isolated from the Castanopsis indica leaves. This study explored the apoptogenic mechanistic studies of BSSG against Ehrlich's ascites carcinoma (EAC) treated mice through morphological study, comet assay, flow cytometry (FACS) and Western blotting assay method. AO/EB staining and FACS analysis showed that BSSG possessed apoptosis induction activities on EAC cells. Dose dependent induction of DNA damage was observed after BSSG treatment. Increase the expression of apoptotic protein p53 and p21 in EAC, multiple downstream factors contributing to apoptosis pathway. The increase of caspase-9 and caspase-3 activities revealed that caspase was a key mediator of the apoptotic pathway induced by BSSG, and up-regulation of Bax and down-regulation of anti-apoptotic protein Bcl-2 resulted in the decrease of Bcl-2/Bax ratio. Owing to the combination of significant antitumour activity by inducing apoptosis, BSSG holds the promise of being an interesting chemo-preventive agent active in cancer therapy.

The role of c-Jun in controlling the EPAC1-dependent induction of the SOCS3 gene in HUVECs.

PubMed

Wiejak, Jolanta; Dunlop, Julia; Yarwood, Stephen J

2014-05-02

The cyclic AMP sensor, EPAC1, activates AP1-mediated transcription in HUVECs. Correspondingly, induction of the SOCS3 minimal promoter by EPAC1 requires a single AP1 site that constitutively binds phosphorylated (Ser63) c-Jun in DNA-pull-down assays. c-Jun (Ser63) becomes further phosphorylated following cyclic AMP stimulation and specific activation of protein kinase A (PKA), but not through selective activation of EPAC1. Moreover, despite a requirement for c-Jun for SOCS3 induction in fibroblasts, phospho-null c-Jun (Ser63/73Ala) had little effect on SOCS3 induction by cyclic AMP in HUVECs. AP1 activation and SOCS3 induction by EPAC1 in HUVECs therefore occur independently of c-Jun phosphorylation on Ser63. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Organizer formation in Hydra is disrupted by thalidomide treatment.

PubMed

Brooun, Maria; Manoukian, Armen; Shimizu, Hiroshi; Bode, Hans R; McNeill, Helen

2013-06-01

Thalidomide is a drug that is well known for its teratogenic properties in humans. Surprisingly, thalidomide does not have teratogenic effects on mouse development. We investigated the effect of thalidomide on patterning in hydra, an early metazoan with a very simple axial symmetry. Hydra develops asexually via Wnt-dependent organizer formation, leading to the budding of a new organism. We observe both induction and inhibition of organizer formation depending on cellular context. Interestingly, thalidomide treatment altered budding and the developing organizer, but had little effect on the adult. Expression of Hybra1, a marker of the organizer increased upon thalidomide treatment. However when the organizer is induced by ectopic activation of Wnt signaling via GSK3 inhibition, thalidomide suppresses induction. We show that inhibition of Wnt signaling is not mediated by induction of the BMP pathway. We show that thalidomide activity on organizer formation in hydra depends on the activity of casein kinase1 and the abundance of β-catenin. Finally, we find that interstitial cells, multipotent cells which give rise to nemoatocytes, neural, digestive and germline cells, are partially responsible for the inhibitory effect of thalidomide. Copyright © 2013 Elsevier Inc. All rights reserved.

Situational and structural variation in youth perceptions of maternal guilt induction.

PubMed

Rote, Wendy M; Smetana, Judith G

2017-10-01

Parental induction of empathy-related guilt plays an important role in children's moral development. However, guilt induction can also be psychologically controlling and detrimental for youth adjustment. This study provided a more nuanced view of parental guilt induction by examining how the nature of a child's misdeed and the structure and content of the parental guilt inductive statement impact children's perceptions of it. Using hypothetical vignettes, this study experimentally examined the impact of the type (domain) of child behavior, highlighted victim, and focus of parental criticism on 156 children's and early and middle adolescents' (age: Ms = 8.82, 12.11, and 15.84 years) perceptions of maternal guilt induction. Attributions of guilt and shame increased most for younger children, when mothers focused on indirect harm to themselves about personal issues, and when mothers criticized their child as a person (shame only). Youth evaluated guilt induction least positively for personal issues and when mothers criticized the child's personality while focusing on indirect harm to themselves. With age, youth were less accepting of maternal guilt induction and more likely to endorse negative and parent-centered intentions, especially for personal issues. Older youth also drew less distinction between guilt induction over multifaceted and personal issues. Guilt induction over moral issues was generally perceived most positively. Additional interactions also emerged. These findings suggest that the meaning and effects of guilt induction on children's development may depend on the way in which it is enacted. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Biolistic transformation of cotton embryogenic cell suspension cultures

USDA-ARS?s Scientific Manuscript database

Genetic transformation of cotton is highly dependent on the ability to regenerate fertile plants from transgenic cells through somatic embryogenesis. Induction of embryogenic cell cultures is genotype-dependant. However, once embryogenic cell cultures are available, they can be effectively used fo...

Increased glycosylation efficiency of recombinant proteins in Escherichia coli by auto-induction.

PubMed

Ding, Ning; Yang, Chunguang; Sun, Shenxia; Han, Lichi; Ruan, Yao; Guo, Longhua; Hu, Xuejun; Zhang, Jianing

2017-03-25

Escherichia coli cells have been considered as promising hosts for producing N-glycosylated proteins since the successful production of N-glycosylated protein in E. coli with the pgl (N-linked protein glycosylation) locus from Campylobacter jejuni. However, one hurdle in producing N-glycosylated proteins in large scale using E. coli is inefficient glycan glycosylation. In this study, we developed a strategy for the production of N-glycosylated proteins with high efficiency via an optimized auto-induction method. The 10th human fibronectin type III domain (FN3) was engineered with native glycosylation sequon DFNRSK and optimized DQNAT sequon in C-terminus with flexible linker as acceptor protein models. The resulting glycosylation efficiencies were confirmed by Western blots with anti-FLAG M1 antibody. Increased efficiency of glycosylation was obtained by changing the conventional IPTG induction to auto-induction method, which increased the glycosylation efficiencies from 60% and 75% up to 90% and 100% respectively. Moreover, in the condition of inserting the glycosylation sequon in the loop of FN3 (the acceptor sequon with local structural conformation), the glycosylation efficiency was increased from 35% to 80% by our optimized auto-induction procedures. To justify the potential for general application of the optimized auto-induction method, the reconstituted lsg locus from Haemophilus influenzae and PglB from C. jejuni were utilized, and this led to 100% glycosylation efficiency. Our studies provided quantitative evidence that the optimized auto-induction method will facilitate the large-scale production of pure exogenous N-glycosylation proteins in E. coli cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Vitamin K2 alleviates type 2 diabetes in rats by induction of osteocalcin gene expression.

PubMed

Hussein, Atef G; Mohamed, Randa H; Shalaby, Sally M; Abd El Motteleb, Dalia M

2018-03-01

The biological mechanisms behind the association between vitamin K (Vit K) and glucose metabolism are uncertain. We aimed to analyze the expression of insulin 1 (Ins 1), insulin 2 (Ins 2) and cyclin D2, the expression of adiponectin and UCP-1 . In addition, we aimed to estimate the doses of Vit K2 able to affect various aspects of glucose and energy metabolism in type 2 diabetes. Thirty adult male rats were allocated equally into five groups: control group, diabetes mellitus group, and groups 3, 4, and 5, which received Vit K 2 at three daily dose levels (10, 15, and 30 mg/kg, respectively) for 8 wk. At the end of the study, blood samples were collected to quantify total osteocalcin, fasting plasma glucose, fasting insulin, and relevant variables. The expression of OC, Ins 1, Ins 2, cyclin D2, adiponectin, UCP-1 genes was analyzed by real-time polymerase chain reaction. After administration of Vit K 2 , a dose-dependent decrease in fasting plasma glucose, hemoglobin A1c and homeostatic model assessment method insulin resistance, and a dose-dependent increase in fasting insulin and homeostatic model assessment method β cell function levels, when compared with diabetes mellitus rats, were detected. There was significant upregulation of OC, Ins 1, Ins 2, or cyclin D2 gene expression in the three treated groups in a dose-dependent manner when compared with the diabetic rats. However, expression of adiponectin and UCP-1 were significantly increased at the highest dose (30 mg/kg daily) only. Vit K 2 administration could improve glycemic status in type 2 diabetic rats by induction of OC gene expression. Osteocalcin could increase β-cell proliferation, energy expenditure, and adiponectin expression. Different concentrations of Vit K 2 were required to affect glucose metabolism and insulin sensitivity. Copyright © 2017 Elsevier Inc. All rights reserved.

Use of labour induction and risk of cesarean delivery: a systematic review and meta-analysis

PubMed Central

Mishanina, Ekaterina; Rogozinska, Ewelina; Thatthi, Tej; Uddin-Khan, Rehan; Khan, Khalid S.; Meads, Catherine

2014-01-01

Background: Induction of labour is common, and cesarean delivery is regarded as its major complication. We conducted a systematic review and meta-analysis to investigate whether the risk of cesarean delivery is higher or lower following labour induction compared with expectant management. Methods: We searched 6 electronic databases for relevant articles published through April 2012 to identify randomized controlled trials (RCTs) in which labour induction was compared with placebo or expectant management among women with a viable singleton pregnancy. We assessed risk of bias and obtained data on rates of cesarean delivery. We used regression analysis techniques to explore the effect of patient characteristics, induction methods and study quality on risk of cesarean delivery. Results: We identified 157 eligible RCTs (n = 31 085). Overall, the risk of cesarean delivery was 12% lower with labour induction than with expectant management (pooled relative risk [RR] 0.88, 95% confidence interval [CI] 0.84–0.93; I2 = 0%). The effect was significant in term and post-term gestations but not in preterm gestations. Meta-regression analysis showed that initial cervical score, indication for induction and method of induction did not alter the main result. There was a reduced risk of fetal death (RR 0.50, 95% CI 0.25–0.99; I2 = 0%) and admission to a neonatal intensive care unit (RR 0.86, 95% CI 0.79–0.94), and no impact on maternal death (RR 1.00, 95% CI 0.10–9.57; I2 = 0%) with labour induction. Interpretation: The risk of cesarean delivery was lower among women whose labour was induced than among those managed expectantly in term and post-term gestations. There were benefits for the fetus and no increased risk of maternal death. PMID:24778358

Higher-order correlations for fluctuations in the presence of fields.

PubMed

Boer, A; Dumitru, S

2002-10-01

The higher-order moments of the fluctuations for thermodynamic systems in the presence of fields are investigated in the framework of a theoretical method. The method uses a generalized statistical ensemble consistent with an adequate expression for the internal energy. The applications refer to the case of a system in a magnetoquasistatic field. In the case of linear magnetic media, one finds that, for the description of the magnetic induction fluctuations, the Gaussian approximation is satisfactory. For nonlinear media, the corresponding fluctuations are non-Gaussian, having a non-null asymmetry. Furthermore, the respective fluctuations have characteristics of leptokurtic, mesokurtic and platykurtic type, depending on the value of the magnetic field strength as compared with a scaling factor of the magnetization curve.

On the analysis of using 3-coil wireless power transfer system in retinal prosthesis.

PubMed

Bai, Shun; Skafidas, Stan

2014-01-01

Designing a wireless power transmission system(WPTS) using inductive coupling has been investigated extensively in the last decade. Depending on the different configurations of the coupling system, there have been various designing methods to optimise the power transmission efficiency based on the tuning circuitry, quality factor optimisation and geometrical configuration. Recently, a 3-coil WPTS was introduced in retinal prosthesis to overcome the low power transferring efficiency due to low coupling coefficient. Here we present a method to analyse this 3-coil WPTS using the S-parameters to directly obtain maximum achievable power transferring efficiency. Through electromagnetic simulation, we brought a question on the condition of improvement using 3-coil WPTS in powering retinal prosthesis.

CYTOCHROMES P450 (CYP) IN THE POECILIOPSIS LUCIDA HEPATOCELLULAR CARCINOMA CELL LINE (PLHC-1): DOSE- AND TIME-DEPENDENT GLUCOCORTICOID POTENTIATION OF CYP1A INDUCTION WITHOUT INDUCTION OF CYP3A. (R823889)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Distinct Single but Not Necessarily Repeated Tetanization Is Required to Induce Hippocampal Late-LTP in the Rat CA1

ERIC Educational Resources Information Center

Sajikumar, Sreedharan; Navakkode, Sheeja; Frey, Julietta U.

2008-01-01

The protein synthesis-dependent form of hippocampal long-term potentiation (late-LTP) is thought to underlie memory. Its induction requires a distinct stimulation strength, and the common opinion is that only repeated tetani result in late-LTP whereas as single tetanus only reveals a transient early-LTP. Properties of LTP induction were compared…

Methadone induction in primary care for opioid dependence: a pragmatic randomized trial (ANRS Methaville).

PubMed

Carrieri, Patrizia Maria; Michel, Laurent; Lions, Caroline; Cohen, Julien; Vray, Muriel; Mora, Marion; Marcellin, Fabienne; Spire, Bruno; Morel, Alain; Roux, Perrine

2014-01-01

Methadone coverage is poor in many countries due in part to methadone induction being possible only in specialized care (SC). This multicenter pragmatic trial compared the effectiveness of methadone treatment between two induction models: primary care (PC) and SC. In this study, registered at ClinicalTrials.Gov (NCT00657397), opioid-dependent individuals not on methadone treatment for at least one month or receiving buprenorphine but needing to switch were randomly assigned to start methadone in PC (N = 155) or in SC (N = 66) in 10 sites in France. Visits were scheduled at months M0, M3, M6 and M12. The primary outcome was self-reported abstinence from street-opioids at 12 months (M12) (with an underlying 15% non-inferiority hypothesis for PC). Secondary outcomes were abstinence during follow-up, engagement in treatment (i.e. completing the induction period), retention and satisfaction with the explanations provided by the physician. Primary analysis used intention to treat (ITT). Mixed models and the log-rank test were used to assess the arm effect (PC vs. SC) on the course of abstinence and retention, respectively. In the ITT analysis (n = 155 in PC, 66 in SC), which compared the proportions of street-opioid abstinent participants, 85/155 (55%) and 22/66 (33%) of the participants were classified as street-opioid abstinent at M12 in PC and SC, respectively. This ITT analysis showed the non-inferiority of PC (21.5 [7.7; 35.3]). Engagement in treatment and satisfaction with the explanations provided by the physician were significantly higher in PC than SC. Retention in methadone and abstinence during follow-up were comparable in both arms (p = 0.47, p = 0.39, respectively). Under appropriate conditions, methadone induction in primary care is feasible and acceptable to both physicians and patients. It is as effective as induction in specialized care in reducing street-opioid use and ensuring engagement and retention in treatment for opioid dependence. Number Eudract 2008-001338-28; ClinicalTrials.gov: NCT00657397; International Standard Randomized Controlled Trial Number Register ISRCTN31125511.

Hepatitis C virus controls interferon production through PKR activation.

PubMed

Arnaud, Noëlla; Dabo, Stéphanie; Maillard, Patrick; Budkowska, Agata; Kalliampakou, Katerina I; Mavromara, Penelope; Garcin, Dominique; Hugon, Jacques; Gatignol, Anne; Akazawa, Daisuke; Wakita, Takaji; Meurs, Eliane F

2010-05-11

Hepatitis C virus is a poor inducer of interferon (IFN), although its structured viral RNA can bind the RNA helicase RIG-I, and activate the IFN-induction pathway. Low IFN induction has been attributed to HCV NS3/4A protease-mediated cleavage of the mitochondria-adapter MAVS. Here, we have investigated the early events of IFN induction upon HCV infection, using the cell-cultured HCV JFH1 strain and the new HCV-permissive hepatoma-derived Huh7.25.CD81 cell subclone. These cells depend on ectopic expression of the RIG-I ubiquitinating enzyme TRIM25 to induce IFN through the RIG-I/MAVS pathway. We observed induction of IFN during the first 12 hrs of HCV infection, after which a decline occurred which was more abrupt at the protein than at the RNA level, revealing a novel HCV-mediated control of IFN induction at the level of translation. The cellular protein kinase PKR is an important regulator of translation, through the phosphorylation of its substrate the eIF2alpha initiation factor. A comparison of the expression of luciferase placed under the control of an eIF2alpha-dependent (IRES(EMCV)) or independent (IRES(HCV)) RNA showed a specific HCV-mediated inhibition of eIF2alpha-dependent translation. We demonstrated that HCV infection triggers the phosphorylation of both PKR and eIF2alpha at 12 and 15 hrs post-infection. PKR silencing, as well as treatment with PKR pharmacological inhibitors, restored IFN induction in JFH1-infected cells, at least until 18 hrs post-infection, at which time a decrease in IFN expression could be attributed to NS3/4A-mediated MAVS cleavage. Importantly, both PKR silencing and PKR inhibitors led to inhibition of HCV yields in cells that express functional RIG-I/MAVS. In conclusion, here we provide the first evidence that HCV uses PKR to restrain its ability to induce IFN through the RIG-I/MAVS pathway. This opens up new possibilities to assay PKR chemical inhibitors for their potential to boost innate immunity in HCV infection.

Hepatitis C Virus Controls Interferon Production through PKR Activation

PubMed Central

Arnaud, Noëlla; Dabo, Stéphanie; Maillard, Patrick; Budkowska, Agata; Kalliampakou, Katerina I.; Mavromara, Penelope; Garcin, Dominique; Hugon, Jacques; Gatignol, Anne; Akazawa, Daisuke; Wakita, Takaji; Meurs, Eliane F.

2010-01-01

Hepatitis C virus is a poor inducer of interferon (IFN), although its structured viral RNA can bind the RNA helicase RIG-I, and activate the IFN-induction pathway. Low IFN induction has been attributed to HCV NS3/4A protease-mediated cleavage of the mitochondria-adapter MAVS. Here, we have investigated the early events of IFN induction upon HCV infection, using the cell-cultured HCV JFH1 strain and the new HCV-permissive hepatoma-derived Huh7.25.CD81 cell subclone. These cells depend on ectopic expression of the RIG-I ubiquitinating enzyme TRIM25 to induce IFN through the RIG-I/MAVS pathway. We observed induction of IFN during the first 12 hrs of HCV infection, after which a decline occurred which was more abrupt at the protein than at the RNA level, revealing a novel HCV-mediated control of IFN induction at the level of translation. The cellular protein kinase PKR is an important regulator of translation, through the phosphorylation of its substrate the eIF2α initiation factor. A comparison of the expression of luciferase placed under the control of an eIF2α-dependent (IRESEMCV) or independent (IRESHCV) RNA showed a specific HCV-mediated inhibition of eIF2α-dependent translation. We demonstrated that HCV infection triggers the phosphorylation of both PKR and eIF2α at 12 and 15 hrs post-infection. PKR silencing, as well as treatment with PKR pharmacological inhibitors, restored IFN induction in JFH1-infected cells, at least until 18 hrs post-infection, at which time a decrease in IFN expression could be attributed to NS3/4A-mediated MAVS cleavage. Importantly, both PKR silencing and PKR inhibitors led to inhibition of HCV yields in cells that express functional RIG-I/MAVS. In conclusion, here we provide the first evidence that HCV uses PKR to restrain its ability to induce IFN through the RIG-I/MAVS pathway. This opens up new possibilities to assay PKR chemical inhibitors for their potential to boost innate immunity in HCV infection. PMID:20485506

Hepatitis C Virus Reveals a Novel Early Control in Acute Immune Response

PubMed Central

Arnaud, Noëlla; Dabo, Stéphanie; Akazawa, Daisuke; Fukasawa, Masayoshi; Shinkai-Ouchi, Fumiko; Hugon, Jacques; Wakita, Takaji; Meurs, Eliane F.

2011-01-01

Recognition of viral RNA structures by the intracytosolic RNA helicase RIG-I triggers induction of innate immunity. Efficient induction requires RIG-I ubiquitination by the E3 ligase TRIM25, its interaction with the mitochondria-bound MAVS protein, recruitment of TRAF3, IRF3- and NF-κB-kinases and transcription of Interferon (IFN). In addition, IRF3 alone induces some of the Interferon-Stimulated Genes (ISGs), referred to as early ISGs. Infection of hepatocytes with Hepatitis C virus (HCV) results in poor production of IFN despite recognition of the viral RNA by RIG-I but can lead to induction of early ISGs. HCV was shown to inhibit IFN production by cleaving MAVS through its NS3/4A protease and by controlling cellular translation through activation of PKR, an eIF2α-kinase containing dsRNA-binding domains (DRBD). Here, we have identified a third mode of control of IFN induction by HCV. Using HCVcc and the Huh7.25.CD81 cells, we found that HCV controls RIG-I ubiquitination through the di-ubiquitine-like protein ISG15, one of the early ISGs. A transcriptome analysis performed on Huh7.25.CD81 cells silenced or not for PKR and infected with JFH1 revealed that HCV infection leads to induction of 49 PKR-dependent genes, including ISG15 and several early ISGs. Silencing experiments revealed that this novel PKR-dependent pathway involves MAVS, TRAF3 and IRF3 but not RIG-I, and that it does not induce IFN. Use of PKR inhibitors showed that this pathway requires the DRBD but not the kinase activity of PKR. We then demonstrated that PKR interacts with HCV RNA and MAVS prior to RIG-I. In conclusion, HCV recruits PKR early in infection as a sensor to trigger induction of several IRF3-dependent genes. Among those, ISG15 acts to negatively control the RIG-I/MAVS pathway, at the level of RIG-I ubiquitination.These data give novel insights in the machinery involved in the early events of innate immune response. PMID:22022264

Magnetoacoustic Tomography with Magnetic Induction (MAT-MI) for Breast Tumor Imaging: Numerical Modeling and Simulation

PubMed Central

Zhou, Lian; Li, Xu; Zhu, Shanan; He, Bin

2011-01-01

Magnetoacoustic tomography with magnetic induction (MAT-MI) was recently introduced as a noninvasive electrical conductivity imaging approach with high spatial resolution close to ultrasound imaging. In the present study, we test the feasibility of the MAT-MI method for breast tumor imaging using numerical modeling and computer simulation. Using the finite element method, we have built three dimensional numerical breast models with varieties of embedded tumors for this simulation study. In order to obtain an accurate and stable forward solution that does not have numerical errors caused by singular MAT-MI acoustic sources at conductivity boundaries, we first derive an integral forward method for calculating MAT-MI acoustic sources over the entire imaging volume. An inverse algorithm for reconstructing the MAT-MI acoustic source is also derived with spherical measurement aperture, which simulates a practical setup for breast imaging. With the numerical breast models, we have conducted computer simulations under different imaging parameter setups and all the results suggest that breast tumors that have large conductivity contrast to its surrounding tissues as reported in literature may be readily detected in the reconstructed MAT-MI images. In addition, our simulations also suggest that the sensitivity of imaging breast tumors using the presented MAT-MI setup depends more on the tumor location and the conductivity contrast between the tumor and its surrounding tissues than on the tumor size. PMID:21364262

Analytical estimation on divergence and flutter vibrations of symmetrical three-phase induction stator via field-synchronous coordinates

NASA Astrophysics Data System (ADS)

Xia, Ying; Wang, Shiyu; Sun, Wenjia; Xiu, Jie

2017-01-01

The electromagnetically induced parametric vibration of the symmetrical three-phase induction stator is examined. While it can be analyzed by an approximate analytical or numerical method, more accurate and simple analytical method is desirable. This work proposes a new method based on the field-synchronous coordinates. A mechanical-electromagnetic coupling model is developed under this frame such that a time-invariant governing equation with gyroscopic term can be developed. With the general vibration theory, the eigenvalue is formulated; the transition curves between the stable and unstable regions, and response are all determined as closed-form expressions of basic mechanical-electromagnetic parameters. The dependence of these parameters on the instability behaviors is demonstrated. The results imply that the divergence and flutter instabilities can occur even for symmetrical motors with balanced, constant amplitude and sinusoidal voltage. To verify the analytical predictions, this work also builds up a time-variant model of the same system under the conventional inertial frame. The Floquét theory is employed to predict the parametric instability and the numerical integration is used to obtain the parametric response. The parametric instability and response are both well compared against those under the field-synchronous coordinates. The proposed field-synchronous coordinates allows a quick estimation on the electromagnetically induced vibration. The convenience offered by the body-fixed coordinates is discussed across various fields.

The activation of c-Jun NH2-terminal kinase is required for dihydroartemisinin-induced autophagy in pancreatic cancer cells

PubMed Central

2014-01-01

Background c-Jun NH2-terminal kinases (JNKs) are strongly activated by a stressful cellular environment, such as chemotherapy and oxidative stress. Autophagy is a protein-degradation system in which double-membrane vacuoles called autophagosomes are formed. The autophagy-related gene Beclin 1 plays a key role in this process. We previously found that autophagy was induced by dihydroartemisinin (DHA) in pancreatic cancer cells. However, little is known about the complex relationship between ROS, JNK activation, autophagy induction, and Beclin 1 expression. Methods Cell viability and CCK-8 assays were carried out to determine the cell proliferation; small interfering RNAs (siRNAs) were used to knockdown c-Jun NH2-terminal kinases (JNK1/2) genes; western blot was performed to detect the protein expression of LC3, JNK, Beclin 1, caspase 3 and β-actin; production of intracellular ROS was analyzed using FACS flow cytometry; autophagy induction was confirmed by electron microscopy. Results In the present study, we explored the role of DHA and Beclin 1 expression in autophagy. DHA-treated cells showed autophagy characteristics, and DHA also activated the JNK pathway and up-regulated the expression of Beclin 1. Conversely, blocking JNK signaling inhibited Beclin 1 up-regulation. JNK activation was found to primarily depend on reactive oxygen species (ROS) resulting from the DHA treatment. Moreover, JNK pathway inhibition and Beclin 1 silencing prevented the induction of DHA-induced autophagy. Conclusions These results suggest that the induction of autophagy by DHA is required for JNK-mediated Beclin 1 expression. PMID:24438216

Cocaine Promotes Coincidence Detection and Lowers Induction Threshold during Hebbian Associative Synaptic Potentiation in Prefrontal Cortex.

PubMed

Ruan, Hongyu; Yao, Wei-Dong

2017-01-25

Addictive drugs usurp neural plasticity mechanisms that normally serve reward-related learning and memory, primarily by evoking changes in glutamatergic synaptic strength in the mesocorticolimbic dopamine circuitry. Here, we show that repeated cocaine exposure in vivo does not alter synaptic strength in the mouse prefrontal cortex during an early period of withdrawal, but instead modifies a Hebbian quantitative synaptic learning rule by broadening the temporal window and lowers the induction threshold for spike-timing-dependent LTP (t-LTP). After repeated, but not single, daily cocaine injections, t-LTP in layer V pyramidal neurons is induced at +30 ms, a normally ineffective timing interval for t-LTP induction in saline-exposed mice. This cocaine-induced, extended-timing t-LTP lasts for ∼1 week after terminating cocaine and is accompanied by an increased susceptibility to potentiation by fewer pre-post spike pairs, indicating a reduced t-LTP induction threshold. Basal synaptic strength and the maximal attainable t-LTP magnitude remain unchanged after cocaine exposure. We further show that the cocaine facilitation of t-LTP induction is caused by sensitized D1-cAMP/protein kinase A dopamine signaling in pyramidal neurons, which then pathologically recruits voltage-gated l-type Ca 2+ channels that synergize with GluN2A-containing NMDA receptors to drive t-LTP at extended timing. Our results illustrate a mechanism by which cocaine, acting on a key neuromodulation pathway, modifies the coincidence detection window during Hebbian plasticity to facilitate associative synaptic potentiation in prefrontal excitatory circuits. By modifying rules that govern activity-dependent synaptic plasticity, addictive drugs can derail the experience-driven neural circuit remodeling process important for executive control of reward and addiction. It is believed that addictive drugs often render an addict's brain reward system hypersensitive, leaving the individual more susceptible to relapse. We found that repeated cocaine exposure alters a Hebbian associative synaptic learning rule that governs activity-dependent synaptic plasticity in the mouse prefrontal cortex, characterized by a broader temporal window and a lower threshold for spike-timing-dependent LTP (t-LTP), a cellular form of learning and memory. This rule change is caused by cocaine-exacerbated D1-cAMP/protein kinase A dopamine signaling in pyramidal neurons that in turn pathologically recruits l-type Ca 2+ channels to facilitate coincidence detection during t-LTP induction. Our study provides novel insights on how cocaine, even with only brief exposure, may prime neural circuits for subsequent experience-dependent remodeling that may underlie certain addictive behavior. Copyright © 2017 the authors 0270-6474/17/370986-12$15.00/0.

Steady-state inductive spheromak operation

DOEpatents

Janos, A.C.; Jardin, S.C.; Yamada, M.

1985-02-20

The inductively formed spheromak configuration (S-1) can be maintained in a highly stable and controlled fashion. The method described eliminates the restriction to pulsed spheromak plasmas or the use of electrodes for steady-state operation, and, therefore, is a reactor-relevant formation and sustainment method.

Improving materials and methods for installing inductive loop detectors : final report.

DOT National Transportation Integrated Search

1986-06-01

This report is the final report of this research project. It describes a compiling of materials utilized by various agencies for use in formation of inductive loop detectors. It further lists methods by which different agencies install materials in o...

Induction of labor in a contemporary obstetric cohort.

PubMed

Laughon, S Katherine; Zhang, Jun; Grewal, Jagteshwar; Sundaram, Rajeshwari; Beaver, Julie; Reddy, Uma M

2012-06-01

We sought to describe details of labor induction, including precursors and methods, and associated vaginal delivery rates. This was a retrospective cohort study of 208,695 electronic medical records from 19 hospitals across the United States, 2002 through 2008. Induction occurred in 42.9% of nulliparas and 31.8% of multiparas and elective or no recorded indication for induction at term occurred in 35.5% and 44.1%, respectively. Elective induction at term in multiparas was highly successful (vaginal delivery 97%) compared to nulliparas (76.2%). For all precursors, cesarean delivery was more common in nulliparas in the latent compared to active phase of labor. Regardless of method, vaginal delivery rates were higher with a ripe vs unripe cervix, particularly for multiparas (86.6-100%). Induction of labor was a common obstetric intervention. Selecting appropriate candidates and waiting longer for labor to progress into the active phase would make an impact on decreasing the national cesarean delivery rate. Published by Mosby, Inc.

Induction of Labor in a Contemporary Obstetric Cohort

PubMed Central

Laughon, S. Katherine; Zhang, Jun; Grewal, Jagteshwar; Sundaram, Rajeshwari; Beaver, Julie; Reddy, Uma M.

2012-01-01

Objective To describe details of labor induction, including precursors and methods, and associated vaginal delivery rates. Study Design A retrospective cohort study of 208,695 electronic medical records from 19 hospitals across the United States, 2002–2008. Results Induction occurred in 42.9% of nulliparas and 31.8% of multiparas and elective or no recorded indication for induction at term occurred in 35.5% and 44.1%, respectively. Elective induction at term in multiparas was highly successful (vaginal delivery 97%) compared to nulliparas (76.2%). For all precursors, cesarean delivery was more common in nulliparas in the latent compared to active phase of labor. Regardless of method, vaginal delivery rates were higher with a ripe versus unripe cervix, particularly for multiparas (86.6 – 100%). Conclusions Induction of labor was a common obstetric intervention. Selecting appropriate candidates and waiting longer for labor to progress into the active phase would make an impact on decreasing the national cesarean delivery rate. PMID:22520652

Flexible establishment of functional brain networks supports attentional modulation of unconscious cognition.

PubMed

Ulrich, Martin; Adams, Sarah C; Kiefer, Markus

2014-11-01

In classical theories of attention, unconscious automatic processes are thought to be independent of higher-level attentional influences. Here, we propose that unconscious processing depends on attentional enhancement of task-congruent processing pathways implemented by a dynamic modulation of the functional communication between brain regions. Using functional magnetic resonance imaging, we tested our model with a subliminally primed lexical decision task preceded by an induction task preparing either a semantic or a perceptual task set. Subliminal semantic priming was significantly greater after semantic compared to perceptual induction in ventral occipito-temporal (vOT) and inferior frontal cortex, brain areas known to be involved in semantic processing. The functional connectivity pattern of vOT varied depending on the induction task and successfully predicted the magnitude of behavioral and neural priming. Together, these findings support the proposal that dynamic establishment of functional networks by task sets is an important mechanism in the attentional control of unconscious processing. © 2014 Wiley Periodicals, Inc.

Aquatide Activation of SIRT1 Reduces Cellular Senescence through a SIRT1-FOXO1-Autophagy Axis.

PubMed

Lim, Chae Jin; Lee, Yong-Moon; Kang, Seung Goo; Lim, Hyung W; Shin, Kyong-Oh; Jeong, Se Kyoo; Huh, Yang Hoon; Choi, Suin; Kor, Myungho; Seo, Ho Seong; Park, Byeong Deog; Park, Keedon; Ahn, Jeong Keun; Uchida, Yoshikazu; Park, Kyungho

2017-09-01

Ultraviolet (UV) irradiation is a relevant environment factor to induce cellular senescence and photoaging. Both autophagy- and silent information regulator T1 (SIRT1)-dependent pathways are critical cellular processes of not only maintaining normal cellular functions, but also protecting cellular senescence in skin exposed to UV irradiation. In the present studies, we investigated whether modulation of autophagy induction using a novel synthetic SIRT1 activator, heptasodium hexacarboxymethyl dipeptide-12 (named as Aquatide), suppresses the UVB irradiation-induced skin aging. Treatment with Aquatide directly activates SIRT1 and stimulates autophagy induction in cultured human dermal fibroblasts. Next, we found that Aquatide-mediated activation of SIRT1 increases autophagy induction via deacetylation of forkhead box class O (FOXO) 1. Finally, UVB irradiation-induced cellular senescence measured by SA-β-gal staining was significantly decreased in cells treated with Aquatide in parallel to occurring SIRT1 activation-dependent autophagy. Together, Aquatide modulates autophagy through SIRT1 activation, contributing to suppression of skin aging caused by UV irradiation.

Cardiogenic programming of human pluripotent stem cells by dose-controlled activation of EOMES.

PubMed

Pfeiffer, Martin J; Quaranta, Roberto; Piccini, Ilaria; Fell, Jakob; Rao, Jyoti; Röpke, Albrecht; Seebohm, Guiscard; Greber, Boris

2018-01-30

Master cell fate determinants are thought to induce specific cell lineages in gastrulation by orchestrating entire gene programs. The T-box transcription factor EOMES (eomesodermin) is crucially required for the development of the heart-yet it is equally important for endoderm specification suggesting that it may act in a context-dependent manner. Here, we define an unrecognized interplay between EOMES and the WNT signaling pathway in controlling cardiac induction by using loss and gain-of-function approaches in human embryonic stem cells. Dose-dependent EOMES induction alone can fully replace a cocktail of signaling molecules otherwise essential for the specification of cardiogenic mesoderm. Highly efficient cardiomyocyte programming by EOMES mechanistically involves autocrine activation of canonical WNT signaling via the WNT3 ligand, which necessitates a shutdown of this axis at a subsequent stage. Our findings provide insights into human germ layer induction and bear biotechnological potential for the robust production of cardiomyocytes from engineered stem cells.

Minoxidil Induction of VEGF Is Mediated by Inhibition of HIF-Prolyl Hydroxylase

PubMed Central

Yum, Soohwan; Jeong, Seongkeun; Kim, Dohoon; Lee, Sunyoung; Kim, Wooseong; Yoo, Jin-Wook; Kwon, Oh Sang; Kim, Dae-Duk; Min, Do Sik; Jung, Yunjin

2017-01-01

The topical application of minoxidil may achieve millimolar concentrations in the skin. We investigated whether millimolar minoxidil could induce vascular endothelial growth factor (VEGF), a possible effector for minoxidil-mediated hair growth, and how it occurred at the molecular level. Cell-based experiments were performed to investigate a molecular mechanism underlying the millimolar minoxidil induction of VEGF. The inhibitory effect of minoxidil on hypoxia-inducible factor (HIF) prolyl hydroxylase-2 (PHD-2) was tested by an in vitro von Hippel–Lindau protein (VHL) binding assay. To examine the angiogenic potential of millimolar minoxidil, a chorioallantoic membrane (CAM) assay was used. In human keratinocytes and dermal papilla cells, millimolar minoxidil increased the secretion of VEGF, which was not attenuated by a specific adenosine receptor antagonist that inhibits the micromolar minoxidil induction of VEGF. Millimolar minoxidil induced hypoxia-inducible factor-1α (HIF-1α), and the induction of VEGF was dependent on HIF-1. Moreover, minoxidil applied to the dorsal area of mice increased HIF-1α and VEGF in the skin. In an in vitro VHL binding assay, minoxidil directly inhibited PHD-2, thus preventing the hydroxylation of cellular HIF-1α and VHL-dependent proteasome degradation and resulting in the stabilization of HIF-1α protein. Minoxidil inhibition of PHD-2 was reversed by ascorbate, a cofactor of PHD-2, and the minoxidil induction of cellular HIF-1α was abrogated by the cofactor. Millimolar minoxidil promoted angiogenesis in the CAM assay, an in vivo angiogenic test, and this was nullified by the specific inhibition of VEGF. Our data demonstrate that PHD may be the molecular target for millimolar minoxidil-mediated VEGF induction via HIF-1. PMID:29295567

Carprofen Induction of p75NTR Dependent Apoptosis via the p38 MAPK Pathway in Prostate Cancer Cells

PubMed Central

Khwaja, Fatima S.; Quann, Emily J.; Pattabiraman, Nagarajan; Wynne, Shehla; Djakiew, Daniel

2008-01-01

The p75NTR functions as a tumor suppressor in prostate epithelial cells, where its expression declines with progression to malignant cancer. Previously, we demonstrated that treatment with R-flurbiprofen or ibuprofen induced p75NTR expression in several prostate cancer cell lines leading to p75NTR mediated decreased survival. Utilizing the 2-phenyl propionic acid moiety of these profens as a pharmacophore, we screened an in silico data base of 30 million compounds and identified carprofen as having an order of magnitude greater activity for induction of p75NTR levels and inhibition of cell survival. Prostate (PC-3, DU-145) and bladder (T24) cancer cells were more sensitive to carprofen induction of p75NTR associated loss of survival than breast (MCF7) and fibroblast (3T3) cells. Transfection of prostate cell lines with a dominant negative form of p75NTR prior to carprofen treatment partially rescued cell survival demonstrating a cause and effect relationship between carprofen induction of p75NTR levels and inhibition of survival. Carprofen induced apoptotic nuclear fragmentation in prostate but not in MCF7 and 3T3 cells. Furthermore, siRNA knockdown of the p38 MAPK protein prevented induction of p75NTR by carprofen in both prostate cell lines. Carprofen treatment induced phosphorylation of p38 MAPK as early as within 1 minute. Expression of a dominant negative form of MK2, the kinase downstream of p38 MAPK frequently associated with signaling cascades leading to apoptosis, prevented carprofen induction of the p75NTR protein. Collectively, we identify carprofen as a highly potent profen capable of inducing p75NTR dependent apoptosis via the p38 MAPK pathway in prostate cancer cells. PMID:18974393

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

Wieneke, N.; Neuschaefer-Rube, F.; Bode, L.M.

Energy balance is maintained by controlling both energy intake and energy expenditure. Thyroid hormones play a crucial role in regulating energy expenditure. Their levels are adjusted by a tight feedback-controlled regulation of thyroid hormone production/incretion and by their hepatic metabolism. Thyroid hormone degradation has previously been shown to be enhanced by treatment with phenobarbital or other antiepileptic drugs due to a CAR-dependent induction of phase II enzymes of xenobiotic metabolism. We have recently shown, that PPAR{alpha} agonists synergize with phenobarbital to induce another prototypical CAR target gene, CYP2B1. Therefore, it was tested whether a PPAR{alpha} agonist could enhance the phenobarbital-dependentmore » acceleration of thyroid hormone elimination. In primary cultures of rat hepatocytes the apparent half-life of T3 was reduced after induction with a combination of phenobarbital and the PPAR{alpha} agonist WY14643 to a larger extent than after induction with either compound alone. The synergistic reduction of the half-life could be attributed to a synergistic induction of CAR and the CAR target genes that code for enzymes and transporters involved in the hepatic elimination of T3, such as OATP1A1, OATP1A3, UGT1A3 and UGT1A10. The PPAR{alpha}-dependent CAR induction and the subsequent induction of T3-eliminating enzymes might be of physiological significance for the fasting-induced reduction in energy expenditure by fatty acids as natural PPAR{alpha} ligands. The synergism of the PPAR{alpha} agonist WY14643 and phenobarbital in inducing thyroid hormone breakdown might serve as a paradigm for the synergistic disruption of endocrine control by other combinations of xenobiotics.« less

Mood state dependency of dysfunctional attitudes in bipolar affective disorder.

PubMed

Babakhani, Anet; Startup, Mike

2012-01-01

Studies of cognitive styles among euthymic people with bipolar affective disorder (BAD) without use of mood induction techniques to access those cognitive styles give misleading impressions of normality of those cognitions. The aim of this study was to assess dysfunctional attitudes of participants with BAD, and control participants with no previous psychiatric histories, after mood inductions. Sad and happy moods were induced within 49 BAD and 37 controls. Dysfunctional attitudes were measured following mood inductions using the Dysfunctional Attitude Scale-short form (DAS-24), which has three subscales of achievement, interpersonal, and goal attainment. It was hypothesised that within BAD the sad mood induction would help in accessing dysfunctional attitudes in all three domains relative to the happy mood induction. This was supported. It was also hypothesised that the mood inductions would not affect dysfunctional attitudes within controls. This was supported. When diagnosis was entered as a between group variable, achievement dysfunctional attitudes were significantly higher in BAD compared to controls after a happy induction. Both sad and happy moods provoked higher levels of dysfunctional attitudes within BAD. Euphoria may be related to elevated achievement dysfunctional attitudes, raising risk for mania.

Investigation of the Impact of the Upstream Induction Zone on LIDAR Measurement Accuracy for Wind Turbine Control Applications using Large-Eddy Simulation

NASA Astrophysics Data System (ADS)

Simley, Eric; Y Pao, Lucy; Gebraad, Pieter; Churchfield, Matthew

2014-06-01

Several sources of error exist in lidar measurements for feedforward control of wind turbines including the ability to detect only radial velocities, spatial averaging, and wind evolution. This paper investigates another potential source of error: the upstream induction zone. The induction zone can directly affect lidar measurements and presents an opportunity for further decorrelation between upstream wind and the wind that interacts with the rotor. The impact of the induction zone is investigated using the combined CFD and aeroelastic code SOWFA. Lidar measurements are simulated upstream of a 5 MW turbine rotor and the true wind disturbances are found using a wind speed estimator and turbine outputs. Lidar performance in the absence of an induction zone is determined by simulating lidar measurements and the turbine response using the aeroelastic code FAST with wind inputs taken far upstream of the original turbine location in the SOWFA wind field. Results indicate that while measurement quality strongly depends on the amount of wind evolution, the induction zone has little effect. However, the optimal lidar preview distance and circular scan radius change slightly due to the presence of the induction zone.

Prototype learning and dissociable categorization systems in Alzheimer's disease.

PubMed

Heindel, William C; Festa, Elena K; Ott, Brian R; Landy, Kelly M; Salmon, David P

2013-08-01

Recent neuroimaging studies suggest that prototype learning may be mediated by at least two dissociable memory systems depending on the mode of acquisition, with A/Not-A prototype learning dependent upon a perceptual representation system located within posterior visual cortex and A/B prototype learning dependent upon a declarative memory system associated with medial temporal and frontal regions. The degree to which patients with Alzheimer's disease (AD) can acquire new categorical information may therefore critically depend upon the mode of acquisition. The present study examined A/Not-A and A/B prototype learning in AD patients using procedures that allowed direct comparison of learning across tasks. Despite impaired explicit recall of category features in all tasks, patients showed differential patterns of category acquisition across tasks. First, AD patients demonstrated impaired prototype induction along with intact exemplar classification under incidental A/Not-A conditions, suggesting that the loss of functional connectivity within visual cortical areas disrupted the integration processes supporting prototype induction within the perceptual representation system. Second, AD patients demonstrated intact prototype induction but impaired exemplar classification during A/B learning under observational conditions, suggesting that this form of prototype learning is dependent on a declarative memory system that is disrupted in AD. Third, the surprisingly intact classification of both prototypes and exemplars during A/B learning under trial-and-error feedback conditions suggests that AD patients shifted control from their deficient declarative memory system to a feedback-dependent procedural memory system when training conditions allowed. Taken together, these findings serve to not only increase our understanding of category learning in AD, but to also provide new insights into the ways in which different memory systems interact to support the acquisition of categorical knowledge. Copyright © 2013 Elsevier Ltd. All rights reserved.

Prototype Learning and Dissociable Categorization Systems in Alzheimer’s Disease

PubMed Central

Heindel, William C.; Festa, Elena K.; Ott, Brian R.; Landy, Kelly M.; Salmon, David P.

2015-01-01

Recent neuroimaging studies suggest that prototype learning may be mediated by at least two dissociable memory systems depending on the mode of acquisition, with A/Not-A prototype learning dependent upon a perceptual representation system located within posterior visual cortex and A/B prototype learning dependent upon a declarative memory system associated with medial temporal and frontal regions. The degree to which patients with Alzheimer’s disease (AD) can acquire new categorical information may therefore critically depend upon the mode of acquisition. The present study examined A/Not-A and A/B prototype learning in AD patients using procedures that allowed direct comparison of learning across tasks. Despite impaired explicit recall of category features in all tasks, patients showed differential patterns of category acquisition across tasks. First, AD patients demonstrated impaired prototype induction along with intact exemplar classification under incidental A/Not-A conditions, suggesting that the loss of functional connectivity within visual cortical areas disrupted the integration processes supporting prototype induction within the perceptual representation system. Second, AD patients demonstrated intact prototype induction but impaired exemplar classification during A/B learning under observational conditions, suggesting that this form of prototype learning is dependent on a declarative memory system that is disrupted in AD. Third, the surprisingly intact classification of both prototypes and exemplars during A/B learning under trial-and-error feedback conditions suggests that AD patients shifted control from their deficient declarative memory system to a feedback-dependent procedural memory system when training conditions allowed. Taken together, these findings serve to not only increase our understanding of category learning in AD, but to also provide new insights into the ways in which different memory systems interact to support the acquisition of categorical knowledge. PMID:23751172

Ovulation induction in women with polycystic ovary syndrome.

PubMed

Perales-Puchalt, Alfredo; Legro, Richard S

2013-08-01

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility. There are multiple ways to induce ovulation in PCOS patients, which will eventually provide a successful live birth. Each of these treatments varies in aggressiveness and effectiveness. Ranging from lifestyle modifications, through insulin-sensitizing agents, selective estrogen receptor modulators, aromatase inhibitors, gonadotropins, to laparoscopic ovarian drilling and assisted reproductive techniques, each method achieves ovulation induction through different mechanisms of action. This review provides a description and specific characteristics of the different methods used for ovulation induction which can help to design a personalized approach to each PCOS patient, and a general stepwise approach to ovulation induction in these patients. Copyright © 2013 Elsevier Inc. All rights reserved.

Mechanical and Pharmacologic Methods of Labor Induction: A Randomized Controlled Trial

PubMed Central

Levine, Lisa D.; Downes, Katheryne L.; Elovitz, Michal A.; Parry, Samuel; Sammel, Mary D.; Srinivas, Sindhu K

2016-01-01

Objective To evaluate the effectiveness of four commonly used induction methods. Methods This randomized trial compared four induction methods: Misoprostol alone, Foley alone, Misoprostol–cervical Foley concurrently, and Foley–oxytocin concurrently,. Women undergoing labor induction with full term (≥37 weeks), singleton, vertex presenting gestations, with no contraindication to vaginal delivery, intact membranes, Bishop score ≤6, and cervical dilation ≤2cm were included. Women were enrolled only once during the study period. Our primary outcome was time to delivery. Neither patients nor providers were blinded to assigned treatment group since examinations are required for placement of all methods; however, research personnel were blinded during data abstraction. A sample size of 123 per group (N=492) was planned to compare the four groups pairwise (P≤.008), with a 4-hour reduction in delivery time considered clinically meaningful. Results From May 2013 through June 2015, 997 women were screened and 491 were randomized and analyzed. Demographic and clinical characteristics were similar among the four treatment groups. When comparing all induction method groups, combination methods achieved a faster median time to delivery than single-agent methods, (misoprostol–Foley: 13.1 hours, Foley–oxytocin: 14.5 hours, misoprostol: 17.6 hours, Foley: 17.7 hours, p<0.001). When censored for cesarean and adjusting for parity, women who received misoprostol–Foley delivered almost twice as likely to deliver before women who received misoprostol alone (hazard ratio (HR, 95% CI) 1.92 [1.42–2.59]) or Foley alone (HR, 95%CI: 1.87 [1.39–2.52]), whereas Foley–oxytocin was not statistically different from single-agent methods. Conclusion After censoring for cesarean and adjusting for parity, misoprostol–cervical Foley resulted in twice the chance of delivering before either single-agent method. PMID:27824758

Autophagy Enhances Memory Erasure through Synaptic Destabilization.

PubMed

Shehata, Mohammad; Abdou, Kareem; Choko, Kiriko; Matsuo, Mina; Nishizono, Hirofumi; Inokuchi, Kaoru

2018-04-11

There is substantial interest in memory reconsolidation as a target for the treatment of anxiety disorders, such as post-traumatic stress disorder. However, its applicability is restricted by reconsolidation-resistant boundary conditions that constrain the initial memory destabilization. In this study, we investigated whether the induction of synaptic protein degradation through autophagy modulation, a major protein degradation pathway, can enhance memory destabilization upon retrieval and whether it can be used to overcome these conditions. Here, using male mice in an auditory fear reconsolidation model, we showed that autophagy contributes to memory destabilization and its induction can be used to enhance erasure of a reconsolidation-resistant auditory fear memory that depended on AMPAR endocytosis. Using male mice in a contextual fear reconsolidation model, autophagy induction in the amygdala or in the hippocampus enhanced fear or contextual memory destabilization, respectively. The latter correlated with AMPAR degradation in the spines of the contextual memory-ensemble cells. Using male rats in an in vivo LTP reconsolidation model, autophagy induction enhanced synaptic destabilization in an NMDAR-dependent manner. These data indicate that induction of synaptic protein degradation can enhance both synaptic and memory destabilization upon reactivation and that autophagy inducers have the potential to be used as a therapeutic tool in the treatment of anxiety disorders. SIGNIFICANCE STATEMENT It has been reported that inhibiting synaptic protein degradation prevents memory destabilization. However, whether the reverse relation is true and whether it can be used to enhance memory destabilization are still unknown. Here we addressed this question on the behavioral, molecular, and synaptic levels, and showed that induction of autophagy, a major protein degradation pathway, can enhance memory and synaptic destabilization upon reactivation. We also show that autophagy induction can be used to overcome a reconsolidation-resistant memory, suggesting autophagy inducers as a potential therapeutic tool in the treatment of anxiety disorders. Copyright © 2018 the authors 0270-6474/18/383809-14$15.00/0.

Introducing the "TCDD-inducible AhR-Nrf2 gene battery".

PubMed

Yeager, Ronnie L; Reisman, Scott A; Aleksunes, Lauren M; Klaassen, Curtis D

2009-10-01

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces genes via the transcription factor aryl hydrocarbon receptor (AhR), including Cyp1a1, NAD(P)H:quinone oxidoreductase 1 (Nqo1), UDP-glucuronosyltransferase 1a6 (Ugt1a6), and glutathione S-transferase a1 (Gsta1). These genes are referred to as the "AhR gene battery." However, Nqo1 is also considered a prototypical target gene of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2). In mice, TCDD induction of Nrf2 and Nrf2 target, Nqo1, is dependent on AhR, and thus TCDD induction of drug-processing genes may be routed through an AhR-Nrf2 sequence. There has been speculation that Nrf2 may be involved in the TCDD induction of drug-processing genes; however, the data are not definitive. Therefore, to address whether TCDD induction of Nqo1, Ugts, and Gsts is dependent on Nrf2, we conducted the definitive experiment by administering TCDD (50 mug/kg, ip) to Nrf2-null and wild-type (WT) mice and collecting livers 24 h later to quantify the mRNA of drug-processing genes. TCDD induction of Cyp1a1 and Ugt1a1 was similar in WT and Nrf2-null mice, whereas TCDD induction of Ugt1a5 and 1a9 was blunted in Nrf2-null mice. TCDD induced Nqo1, Ugt1a6, 2b34, 2b35, 2b36, UDP-glucuronic acid-synthesizing gene UDP-glucose dehydrogenase, and Gsta1, m1, m2, m3, m6, p2, t2, and microsomal Gst1 in WT mice but not in Nrf2-null mice. Therefore, the present study demonstrates the novel finding that Nrf2 is required for TCDD induction of classical AhR battery genes Nqo1, Ugt1a6, and Gsta1, as well as most Ugt and Gst isoforms in livers of mice.

Systemic Induction of Photosynthesis via Illumination of the Shoot Apex Is Mediated Sequentially by Phytochrome B, Auxin and Hydrogen Peroxide in Tomato1[OPEN

PubMed Central

Guo, Zhixin; Ahammed, Golam Jalal; Wang, Mengmeng; Zhou, Jie; Xia, Xiaojian; Shi, Kai; Yin, Xueren; Chen, Kunsong; Yu, Jingquan; Zhou, Yanhong

2016-01-01

Systemic signaling of upper leaves promotes the induction of photosynthesis in lower leaves, allowing more efficient use of light flecks. However, the nature of the systemic signals has remained elusive. Here, we show that preillumination of the tomato (Solanum lycopersicum) shoot apex alone can accelerate photosynthetic induction in distal leaves and that this process is light quality dependent, where red light promotes and far-red light delays photosynthetic induction. Grafting the wild-type rootstock with a phytochome B (phyB) mutant scion compromised light-induced photosynthetic induction as well as auxin biosynthesis in the shoot apex, auxin signaling, and RESPIRATORY BURST OXIDASE HOMOLOG1 (RBOH1)-dependent hydrogen peroxide (H2O2) production in the systemic leaves. Light-induced systemic H2O2 production in the leaves of the rootstock also was absent in plants grafted with an auxin-resistant diageotropica (dgt) mutant scion. Cyclic electron flow around photosystem I and associated ATP production were increased in the systemic leaves by exposure of the apex to red light. This enhancement was compromised in the systemic leaves of the wild-type rootstock with phyB and dgt mutant scions and also in RBOH1-RNA interference leaves with the wild type as scion. Silencing of ORANGE RIPENING, which encodes NAD(P)H dehydrogenase, compromised the systemic induction of photosynthesis. Taken together, these results demonstrate that exposure to red light triggers phyB-mediated auxin synthesis in the apex, leading to H2O2 generation in systemic leaves. Enhanced H2O2 levels in turn activate cyclic electron flow and ATP production, leading to a faster induction of photosynthetic CO2 assimilation in the systemic leaves, allowing plants better adaptation to the changing light environment. PMID:27550998

Dissociation and serenity induction.

PubMed

Zoellner, Lori A; Sacks, Matthew B; Foa, Edna B

2007-09-01

Dissociation is a common experience during or immediately after a traumatic event; yet, most of the current knowledge regarding dissociation is retrospective in nature. The aim of the present study investigated a non-pharmacological method of dissociative induction with a clinical sample. Participants with PTSD and non-trauma exposed participants were randomly assigned to receive either a dissociative induction, or a serenity induction, based on modified Velten mood induction procedures. Participants receiving the dissociative induction reported higher state-dissociation than those receiving the serenity induction. The PTSD group reported greater state dissociation than the non-trauma exposed group, regardless of induction. State dissociation was related to trait dissociation, PTSD severity, and depression. The present results provide an initial demonstration of the viability for inducing state dissociation in the laboratory with a PTSD sample.

Differential regulation of p65 and c-Rel NF-kappaB transactivating activity by Cot, protein kinase C zeta and NIK protein kinases in CD3/CD28 activated T cells.

PubMed

Sánchez-Valdepeñas, Carmen; Punzón, Carmen; San-Antonio, Belén; Martin, Angel G; Fresno, Manuel

2007-03-01

It has been shown that phosphorylation of p65/RelA and c-Rel plays a role in the regulation of transcriptional activity of NF-kappaB independent on IkappaB degradation. In this study, we show that anti CD3/CD28 activation induces the transactivation activity of both p65/RelA and c-Rel in T cells using Gal4 dependent assays. Moreover, protein kinase C (PKC)zeta, Cot kinase and NF-kappaB-inducing kinase (NIK) seem to be involved in those processes in a different manner. Thus, transfection of dominant negative forms of Cot and PKCzeta inhibits CD3/CD28 induction of Gal4-p65 transactivation, whereas the kinase inactive versions of the 3 kinases inhibit induction of Gal4-c-Rel. Cot induction of Gal4-c-Rel transactivating activity seems to be mediated sequentially through PKCzeta and NIK activation, since dominant negative form of NIK blocks Cot and PKCzeta induction, whereas kinase inactive PKCzeta only blocks Cot activity. In contrast, the contribution of NIK to the transactivation function of p65/RelA seems to be negligible and more importantly NIK-KD did not inhibit induction by Cot and PKCzeta. Besides, the enhancing effect of Cot on Gal4-p65 was not decreased in mouse embryo fibroblasts from NIK deficient aly/aly mice in contrast with a greatest reduction on Gal4-c-Rel. By using Ser to Ala mutants in p65 and c-Rel transactivation domains, PKCzeta and NIK activities seem to be dependent of a restricted set of Ser in both proteins. In contrast, the enhancing effect of Cot seems to be less dependent of a particular set of Ser residues being partially abrogated by mutation of several Ser residues.

Loss of PINK1 attenuates HIF-1α induction by preventing 4E-BP1-dependent switch in protein translation under hypoxia.

PubMed

Lin, William; Wadlington, Natasha L; Chen, Linan; Zhuang, Xiaoxi; Brorson, James R; Kang, Un Jung

2014-02-19

Parkinson's disease (PD) has multiple proposed etiologies with implication of abnormalities in cellular homeostasis ranging from proteostasis to mitochondrial dynamics to energy metabolism. PINK1 mutations are associated with familial PD and here we discover a novel PINK1 mechanism in cellular stress response. Using hypoxia as a physiological trigger of oxidative stress and disruption in energy metabolism, we demonstrate that PINK1(-/-) mouse cells exhibited significantly reduced induction of HIF-1α protein, HIF-1α transcriptional activity, and hypoxia-responsive gene upregulation. Loss of PINK1 impairs both hypoxia-induced 4E-BP1 dephosphorylation and increase in the ratio of internal ribosomal entry site (IRES)-dependent to cap-dependent translation. These data suggest that PINK1 mediates adaptive responses by activating IRES-dependent translation, and the impairments in translation and the HIF-1α pathway may contribute to PINK1-associated PD pathogenesis that manifests under cellular stress.

The Vaccine Adjuvant Chitosan Promotes Cellular Immunity via DNA Sensor cGAS-STING-Dependent Induction of Type I Interferons.

PubMed

Carroll, Elizabeth C; Jin, Lei; Mori, Andres; Muñoz-Wolf, Natalia; Oleszycka, Ewa; Moran, Hannah B T; Mansouri, Samira; McEntee, Craig P; Lambe, Eimear; Agger, Else Marie; Andersen, Peter; Cunningham, Colm; Hertzog, Paul; Fitzgerald, Katherine A; Bowie, Andrew G; Lavelle, Ed C

2016-03-15

The cationic polysaccharide chitosan is an attractive candidate adjuvant capable of driving potent cell-mediated immunity, but the mechanism by which it acts is not clear. We show that chitosan promotes dendritic cell maturation by inducing type I interferons (IFNs) and enhances antigen-specific T helper 1 (Th1) responses in a type I IFN receptor-dependent manner. The induction of type I IFNs, IFN-stimulated genes and dendritic cell maturation by chitosan required the cytoplasmic DNA sensor cGAS and STING, implicating this pathway in dendritic cell activation. Additionally, this process was dependent on mitochondrial reactive oxygen species and the presence of cytoplasmic DNA. Chitosan-mediated enhancement of antigen specific Th1 and immunoglobulin G2c responses following vaccination was dependent on both cGAS and STING. These findings demonstrate that a cationic polymer can engage the STING-cGAS pathway to trigger innate and adaptive immune responses. Copyright © 2016 Elsevier Inc. All rights reserved.

Increased Incidence of Urolithiasis and Bacteremia During Proteus mirabilis and Providencia stuartii Coinfection Due to Synergistic Induction of Urease Activity

PubMed Central

Armbruster, Chelsie E.; Smith, Sara N.; Yep, Alejandra; Mobley, Harry L. T.

2014-01-01

Background. Catheter-associated urinary tract infections (CaUTIs) are the most common hospital-acquired infections worldwide and are frequently polymicrobial. The urease-positive species Proteus mirabilis and Providencia stuartii are two of the leading causes of CaUTIs and commonly co-colonize catheters. These species can also cause urolithiasis and bacteremia. However, the impact of coinfection on these complications has never been addressed experimentally. Methods. A mouse model of ascending UTI was utilized to determine the impact of coinfection on colonization, urolithiasis, and bacteremia. Mice were infected with P. mirabilis or a urease mutant, P. stuartii, or a combination of these organisms. In vitro experiments were conducted to assess growth dynamics and impact of co-culture on urease activity. Results. Coinfection resulted in a bacterial load similar to monospecies infection but with increased incidence of urolithiasis and bacteremia. These complications were urease-dependent as they were not observed during coinfection with a P. mirabilis urease mutant. Furthermore, total urease activity was increased during co-culture. Conclusions. We conclude that P. mirabilis and P. stuartii coinfection promotes urolithiasis and bacteremia in a urease-dependent manner, at least in part through synergistic induction of urease activity. These data provide a possible explanation for the high incidence of bacteremia resulting from polymicrobial CaUTI. PMID:24280366

Imaging Metals in Brain Tissue by Laser Ablation - Inductively Coupled Plasma - Mass Spectrometry (LA-ICP-MS)

PubMed Central

Hare, Dominic J.; Kysenius, Kai; Paul, Bence; Knauer, Beate; Hutchinson, Robert W.; O'Connor, Ciaran; Fryer, Fred; Hennessey, Tom P.; Bush, Ashley I.; Crouch, Peter J.; Doble, Philip A.

2017-01-01

Metals are found ubiquitously throughout an organism, with their biological role dictated by both their chemical reactivity and abundance within a specific anatomical region. Within the brain, metals have a highly compartmentalized distribution, depending on the primary function they play within the central nervous system. Imaging the spatial distribution of metals has provided unique insight into the biochemical architecture of the brain, allowing direct correlation between neuroanatomical regions and their known function with regard to metal-dependent processes. In addition, several age-related neurological disorders feature disrupted metal homeostasis, which is often confined to small regions of the brain that are otherwise difficult to analyze. Here, we describe a comprehensive method for quantitatively imaging metals in the mouse brain, using laser ablation - inductively coupled plasma - mass spectrometry (LA-ICP-MS) and specially designed image processing software. Focusing on iron, copper and zinc, which are three of the most abundant and disease-relevant metals within the brain, we describe the essential steps in sample preparation, analysis, quantitative measurements and image processing to produce maps of metal distribution within the low micrometer resolution range. This technique, applicable to any cut tissue section, is capable of demonstrating the highly variable distribution of metals within an organ or system, and can be used to identify changes in metal homeostasis and absolute levels within fine anatomical structures. PMID:28190025

INDUCTION AND SUPPRESSION OF CYTOCHROME P450 1A BY 3,3', 4,4', 5-PENTACHLOROBIPHENYL AND ITS RELATIONSHIP TO OXIDATIVE STRESS IN THE MARINE FISH SCUP (STENOTOMUS CHRYSOPS). (R827102)

EPA Science Inventory

Abstract

The planar polychlorinated biphenyl (PCB) 3,3',4,4'-tetrachlorobiphenyl (TCB) causes dose-dependent induction and post-transcriptional suppression of hepatic cytochrome P450 1A (CYP1A) in the marine teleost scup (Stenotomus chrysops). That suppr...

Critical induction a key quantity for the optimisation of transformer core operation

NASA Astrophysics Data System (ADS)

Ilo, A.; Pfützner, H.; Nakata, T.

2000-06-01

No-load losses P of transformers core have been considerably decreased through introduction of the so-called multi-step-lap designs. However, profound guidelines for the optimum step-number N do not exist. This study shows that the combination of both N and working induction B characterises the flux distribution. Transformer cores can operate in an over or an under-critical way depending on N and B.

Induction of apoptosis in human promyelocytic leukemia HL-60 cells by Ampelopsis cantoniensis crude extract.

PubMed

Tan, Tzu-Wei; Tsai, Huei-Yann; Chen, Yuh-Fung; Chung, Jing-Gung

2004-01-01

The crude extract of Ampelopsis cantoniensis induced apoptosis in human promyelocytic leukemia HL-60 cells and this induction was investigated by flow cytometric analysis, DNA gel electrophoresis and poly (ADP-ribose) fluorescence staining. The results demonstrated that this extract induced dose-dependent cytotoxicity and apoptosis. The level of active caspase-3 was increased after treatment with the crude extract for 24 hours.

The Relationship between Mathematical Induction, Proposition Functions, and Implication Functions

ERIC Educational Resources Information Center

Andrew, Lane

2010-01-01

In this study, I explored the relationship between mathematical induction ability and proposition and implication functions through a mixed methods approach. Students from three universities (N = 78) and 6 classrooms completed a written assessment testing their conceptual and procedural capabilities with induction and functions. In addition, I…

New-Teacher Induction 2.0

ERIC Educational Resources Information Center

Taranto, Greg

2011-01-01

The purpose of this program evaluation study was to design, implement, and evaluate the effectiveness of incorporating an online learning community as part of a comprehensive new-teacher induction program. The researcher, who serves as the middle school principal and new induction coordinator for the school district, used a mixed-method approach…

A randomized trial of misoprostol versus extra-amniotic sodium chloride infusion with oxytocin for induction of labor.

PubMed

Buccellato, C A; Stika, C S; Frederiksen, M C

2000-05-01

Our purpose was to compare the efficacy and safety of misoprostol and extra-amniotic sodium chloride infusion with oxytocin for induction of labor. This randomized trial compared two methods of labor induction in women requiring cervical ripening. One hundred twenty-three women undergoing labor induction with a Bishop score < or =5 were randomly selected to receive either misoprostol, 50 microg intravaginally every 4 hours, or extra-amniotic sodium chloride infusion. The primary outcome variable was the time interval from induction to vaginal delivery. Sixty-one women received extra-amniotic sodium chloride infusion and 62 women received misoprostol. The mean time interval from the start of induction to vaginal delivery was 15.0 +/- 5.0 hours and 16.5 +/- 7.2 hours for the extra-amniotic infusion and misoprostol groups, respectively (P, not significant). The cesarean delivery rate was not significantly different between the 2 groups (32.8% for the extra-amniotic infusion group; 19.4% for the misoprostol group). Maternal and neonatal outcomes were similar between the 2 groups. Both methods of induction are equally efficacious and result in similar maternal and neonatal outcomes.

A tightly coupled non-equilibrium model for inductively coupled radio-frequency plasmas

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

Munafò, A., E-mail: munafo@illinois.edu; Alfuhaid, S. A., E-mail: alfuhai2@illinois.edu; Panesi, M., E-mail: mpanesi@illinois.edu

2015-10-07

The objective of the present work is the development of a tightly coupled magneto-hydrodynamic model for inductively coupled radio-frequency plasmas. Non Local Thermodynamic Equilibrium (NLTE) effects are described based on a hybrid State-to-State approach. A multi-temperature formulation is used to account for thermal non-equilibrium between translation of heavy-particles and vibration of molecules. Excited electronic states of atoms are instead treated as separate pseudo-species, allowing for non-Boltzmann distributions of their populations. Free-electrons are assumed Maxwellian at their own temperature. The governing equations for the electro-magnetic field and the gas properties (e.g., chemical composition and temperatures) are written as a coupled systemmore » of time-dependent conservation laws. Steady-state solutions are obtained by means of an implicit Finite Volume method. The results obtained in both LTE and NLTE conditions over a broad spectrum of operating conditions demonstrate the robustness of the proposed coupled numerical method. The analysis of chemical composition and temperature distributions along the torch radius shows that: (i) the use of the LTE assumption may lead to an inaccurate prediction of the thermo-chemical state of the gas, and (ii) non-equilibrium phenomena play a significant role close the walls, due to the combined effects of Ohmic heating and macroscopic gradients.« less

Temperature-Dependent Characterization, Modeling, and Switching Speed-Limitation Analysis of Third-Generation 10-kV SiC MOSFET

DOE PAGES

Ji, Shiqi; Zheng, Sheng; Wang, Fei; ...

2017-07-06

The temperature-dependent characteristics of the third-generation 10-kV/20-A SiC MOSFET including the static characteristics and switching performance are carried out in this paper. The steady-state characteristics, including saturation current, output characteristics, antiparallel diode, and parasitic capacitance, are tested. Here, a double pulse test platform is constructed including a circuit breaker and gate drive with >10-kV insulation and also a hotplate under the device under test for temperature-dependent characterization during switching transients. The switching performance is tested under various load currents and gate resistances at a 7-kV dc-link voltage from 25 to 125 C and compared with previous 10-kV MOSFETs. A simplemore » behavioral model with its parameter extraction method is proposed to predict the temperature-dependent characteristics of the 10-kV SiC MOSFET. The switching speed limitations, including the reverse recovery of SiC MOSFET's body diode, overvoltage caused by stray inductance, crosstalk, heat sink, and electromagnetic interference to the control are discussed based on simulations and experimental results.« less

Temperature-Dependent Characterization, Modeling, and Switching Speed-Limitation Analysis of Third-Generation 10-kV SiC MOSFET

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

Ji, Shiqi; Zheng, Sheng; Wang, Fei

The temperature-dependent characteristics of the third-generation 10-kV/20-A SiC MOSFET including the static characteristics and switching performance are carried out in this paper. The steady-state characteristics, including saturation current, output characteristics, antiparallel diode, and parasitic capacitance, are tested. Here, a double pulse test platform is constructed including a circuit breaker and gate drive with >10-kV insulation and also a hotplate under the device under test for temperature-dependent characterization during switching transients. The switching performance is tested under various load currents and gate resistances at a 7-kV dc-link voltage from 25 to 125 C and compared with previous 10-kV MOSFETs. A simplemore » behavioral model with its parameter extraction method is proposed to predict the temperature-dependent characteristics of the 10-kV SiC MOSFET. The switching speed limitations, including the reverse recovery of SiC MOSFET's body diode, overvoltage caused by stray inductance, crosstalk, heat sink, and electromagnetic interference to the control are discussed based on simulations and experimental results.« less

Mutual Inductance Problem for a System Consisting of a Current Sheet and a Thin Metal Plate

NASA Technical Reports Server (NTRS)

Fulton, J. P.; Wincheski, B.; Nath, S.; Namkung, M.

1993-01-01

Rapid inspection of aircraft structures for flaws is of vital importance to the commercial and defense aircraft industry. In particular, inspecting thin aluminum structures for flaws is the focus of a large scale R&D effort in the nondestructive evaluation (NDE) community. Traditional eddy current methods used today are effective, but require long inspection times. New electromagnetic techniques which monitor the normal component of the magnetic field above a sample due to a sheet of current as the excitation, seem to be promising. This paper is an attempt to understand and analyze the magnetic field distribution due to a current sheet above an aluminum test sample. A simple theoretical model, coupled with a two dimensional finite element model (FEM) and experimental data will be presented in the next few sections. A current sheet above a conducting sample generates eddy currents in the material, while a sensor above the current sheet or in between the two plates monitors the normal component of the magnetic field. A rivet or a surface flaw near a rivet in an aircraft aluminum skin will disturb the magnetic field, which is imaged by the sensor. Initial results showed a strong dependence of the flaw induced normal magnetic field strength on the thickness and conductivity of the current-sheet that could not be accounted for by skin depth attenuation alone. It was believed that the eddy current imaging method explained the dependence of the thickness and conductivity of the flaw induced normal magnetic field. Further investigation, suggested the complexity associated with the mutual inductance of the system needed to be studied. The next section gives an analytical model to better understand the phenomenon.

Identification and validation of nebulized aerosol devices for sputum induction

PubMed Central

Davidson, Warren J; Dennis, John; The, Stephanie; Litoski, Belinda; Pieron, Cora; Leigh, Richard

2014-01-01

Induced sputum cell count measurement has proven reliability for evaluating airway inflammation in patients with asthma and other airway diseases. Although the use of nebulizer devices for sputum induction is commonplace, they are generally labelled as single-patient devices by the manufacturer and, therefore, cannot be used for multiple patients in large clinical sputum induction programs due to infect ion-control requirements. Accordingly, this study investigated the aerosol characteristics of alternative devices that could be used in such programs. BACKGROUND: Induced sputum cell counts are a noninvasive and reliable method for evaluating the presence, type and degree of airway inflammation in patients with asthma. Currently, standard nebulizer devices used for sputum induction in multiple patients are labelled as single-patient devices by the manufacturer, which conflicts with infection prevention and control requirements. As such, these devices cannot feasibly be used in a clinical sputum induction program. Therefore, there is a need to identify alternative nebulizer devices that are either disposable or labelled for multi-patient use. OBJECTIVE: To apply validated rigorous, scientific testing methods to identify and validate commercially available nebulizer devices appropriate for use in a clinical sputum induction program. METHODS: Measurement of nebulized aerosol output and size for the selected nebulizer designs followed robust International Organization for Standardization methods. Sputum induction using two of these nebulizers was successfully performed on 10 healthy adult subjects. The cytotechnologist performing sputum cell counts was blinded to the type of nebulizer used. RESULTS: The studied nebulizers had variable aerosol outputs. The AeroNeb Solo (Aerogen, Ireland), Omron NE-U17 (Omron, Japan) and EASYneb II (Flaem Nuova, Italy) systems were found to have similar measurements of aerosol size. There was no significant difference in induced sputum cell results between the AeroNeb Solo and EASYneb II devices. DISCUSSION: There is a need for rigorous, scientific evaluation of nebulizer devices for clinical applications, including sputum induction, for measurement of cell counts. CONCLUSION: The present study was the most comprehensive analysis of different nebulizer devices for sputum induction to measure cell counts, and provides a framework for appropriate evaluation of nebulizer devices for induced sputum testing. PMID:24288700

[Fast determination of induction period of motor gasoline using Fourier transform attenuated total reflection infrared spectroscopy].

PubMed

Liu, Ya-Fei; Yuan, Hong-Fu; Song, Chun-Feng; Xie, Jin-Chun; Li, Xiao-Yu; Yan, De-Lin

2014-11-01

A new method is proposed for the fast determination of the induction period of gasoline using Fourier transform attenuated total reflection infrared spectroscopy (ATR-FTIR). A dedicated analysis system with the function of spectral measurement, data processing, display and storage was designed and integrated using a Fourier transform infrared spectrometer module and chemometric software. The sample presentation accessory designed which has advantages of constant optical path, convenient sample injection and cleaning is composed of a nine times reflection attenuated total reflectance (ATR) crystal of zinc selenide (ZnSe) coated with a diamond film and a stainless steel lid with sealing device. The influence of spectral scanning number and repeated sample loading times on the spectral signal-to-noise ratio was studied. The optimum spectral scanning number is 15 times and the optimum sample loading number is 4 times. Sixty four different gasoline samples were collected from the Beijing-Tianjin area and the induction period values were determined as reference data by standard method GB/T 8018-87. The infrared spectra of these samples were collected in the operating condition mentioned above using the dedicated fast analysis system. Spectra were pretreated using mean centering and 1st derivative to reduce the influence of spectral noise and baseline shift A PLS calibration model for the induction period was established by correlating the known induction period values of the samples with their spectra. The correlation coefficient (R2), standard error of calibration (SEC) and standard error of prediction (SEP) of the model are 0.897, 68.3 and 91.9 minutes, respectively. The relative deviation of the model for gasoline induction period prediction is less than 5%, which meets the requirements of repeatability tolerance in GB method. The new method is simple and fast. It takes no more than 3 minutes to detect one sample. Therefore, the method is feasible for implementing fast determination of gasoline induction period, and of a positive meaning in the evaluation of fuel quality.

Intraspecific variation in a generalist herbivore accounts for differential induction and impact of host plant defences

PubMed Central

Kant, Merijn R; Sabelis, Maurice W; Haring, Michel A; Schuurink, Robert C

2007-01-01

Plants and herbivores are thought to be engaged in a coevolutionary arms race: rising frequencies of plants with anti-herbivore defences exert pressure on herbivores to resist or circumvent these defences and vice versa. Owing to its frequency-dependent character, the arms race hypothesis predicts that herbivores exhibit genetic variation for traits that determine how they deal with the defences of a given host plant phenotype. Here, we show the existence of distinct variation within a single herbivore species, the spider mite Tetranychus urticae, in traits that lead to resistance or susceptibility to jasmonate (JA)-dependent defences of a host plant but also in traits responsible for induction or repression of JA defences. We characterized three distinct lines of T. urticae that differentially induced JA-related defence genes and metabolites while feeding on tomato plants (Solanum lycopersicum). These lines were also differently affected by induced JA defences. The first line, which induced JA-dependent tomato defences, was susceptible to those defences; the second line also induced JA defences but was resistant to them; and the third, although susceptible to JA defences, repressed induction. We hypothesize that such intraspecific variation is common among herbivores living in environments with a diversity of plants that impose diverse selection pressure. PMID:18055390

Cyclin K dependent regulation of Aurora B affects apoptosis and proliferation by induction of mitotic catastrophe in prostate cancer.

PubMed

Schecher, Sabrina; Walter, Britta; Falkenstein, Michael; Macher-Goeppinger, Stephan; Stenzel, Philipp; Krümpelmann, Kristina; Hadaschik, Boris; Perner, Sven; Kristiansen, Glen; Duensing, Stefan; Roth, Wilfried; Tagscherer, Katrin E

2017-10-15

Cyclin K plays a critical role in transcriptional regulation as well as cell development. However, the role of Cyclin K in prostate cancer is unknown. Here, we describe the impact of Cyclin K on prostate cancer cells and examine the clinical relevance of Cyclin K as a biomarker for patients with prostate cancer. We show that Cyclin K depletion in prostate cancer cells induces apoptosis and inhibits proliferation accompanied by an accumulation of cells in the G2/M phase. Moreover, knockdown of Cyclin K causes mitotic catastrophe displayed by multinucleation and spindle multipolarity. Furthermore, we demonstrate a Cyclin K dependent regulation of the mitotic kinase Aurora B and provide evidence for an Aurora B dependent induction of mitotic catastrophe. In addition, we show that Cyclin K expression is associated with poor biochemical recurrence-free survival in patients with prostate cancer treated with an adjuvant therapy. In conclusion, targeting Cyclin K represents a novel, promising anti-cancer strategy to induce cell cycle arrest and apoptotic cell death through induction of mitotic catastrophe in prostate cancer cells. Moreover, our results indicate that Cyclin K is a putative predictive biomarker for clinical outcome and therapy response for patients with prostate cancer. © 2017 UICC.

TNF induction of jagged-1 in endothelial cells is NFκB-dependent

PubMed Central

Johnston, Douglas A.; Dong, Bamboo; Hughes, Christopher C.W.

2009-01-01

TNF-α is a potent proinflammatory cytokine that induces endothelial cell (EC) adhesion molecules. In addition, TNF promotes angiogenesis by inducing an EC tip cell phenotype and the expression of jagged-1, a ligand for the notch pathway. Notch signaling is critical for vascular patterning and helps to restrict the proliferation of tip cells. Here we demonstrate that TNF induction of jagged-1 in human EC is rapid and dependent upon signaling through TNFR1, but not TNFR2. A luciferase reporter construct carrying 3.7 kb of 5′ promoter sequence from the human gene was responsive to both TNF and overexpression of NFκB pathway components. TNF-induced promoter activation was blocked by treatment with an NFκB inhibitor or co-expression of dominant-negative IKKβ. Mutations in a putative NFκB-binding site at −3.0 kb, which is conserved across multiple species, resulted in a loss of responsiveness to TNF and NFκB. Electromobility shift and chromatin immunoprecipitation assays revealed binding of both p50 and p65 to the promoter in response to TNF treatment. Full promoter activity also depends on an AP-1 site at −2.0 kb. These results indicate that canonical NFκB signaling is required for TNF induction of the notch ligand jagged-1 in EC. PMID:19393188

CD59 signaling and membrane pores drive Syk-dependent erythrocyte necroptosis

PubMed Central

LaRocca, T J; Stivison, E A; Mal-Sarkar, T; Hooven, T A; Hod, E A; Spitalnik, S L; Ratner, A J

2015-01-01

Mature erythrocytes (red blood cells (RBCs)) undergo the programmed cell death (PCD) pathway of necroptosis in response to bacterial pore-forming toxins (PFTs) that target human CD59 (hCD59) but not hCD59-independent PFTs. Here, we investigate the biochemical mechanism of RBC necroptosis with a focus on the mechanism of induction and the minimal requirements for such RBC death. Binding or crosslinking of the hCD59 receptor led to Syk-dependent induction of vesiculated morphology (echinocytes) that was associated with phosphorylation of Band 3 and was required for Fas ligand (FasL) release. FasL-dependent phosphorylation of receptor-interacting protein kinase 1 (RIP1) in combination with plasma membrane pore formation was required for execution of RBC necroptosis. RIP1 phosphorylation led to the phosphorylation of RIP3, which was also critical for RBC necroptosis. Notably, RBC necroptosis was mediated by FasL and not by other candidate inducers, including tumor necrosis factor alpha (TNF-α) and TNF-related apoptosis-inducing ligand (TRAIL). Other types of RBC damage, such as eryptotic damage, failed to induce necroptosis when combined with hCD59 crosslinking. This work sheds light on the requirements for this recently discovered PCD in RBCs and provides a clear picture of the biochemical mechanism of induction of RBC necroptosis. PMID:26018734

CD59 signaling and membrane pores drive Syk-dependent erythrocyte necroptosis.

PubMed

LaRocca, T J; Stivison, E A; Mal-Sarkar, T; Hooven, T A; Hod, E A; Spitalnik, S L; Ratner, A J

2015-05-28

Mature erythrocytes (red blood cells (RBCs)) undergo the programmed cell death (PCD) pathway of necroptosis in response to bacterial pore-forming toxins (PFTs) that target human CD59 (hCD59) but not hCD59-independent PFTs. Here, we investigate the biochemical mechanism of RBC necroptosis with a focus on the mechanism of induction and the minimal requirements for such RBC death. Binding or crosslinking of the hCD59 receptor led to Syk-dependent induction of vesiculated morphology (echinocytes) that was associated with phosphorylation of Band 3 and was required for Fas ligand (FasL) release. FasL-dependent phosphorylation of receptor-interacting protein kinase 1 (RIP1) in combination with plasma membrane pore formation was required for execution of RBC necroptosis. RIP1 phosphorylation led to the phosphorylation of RIP3, which was also critical for RBC necroptosis. Notably, RBC necroptosis was mediated by FasL and not by other candidate inducers, including tumor necrosis factor alpha (TNF-α) and TNF-related apoptosis-inducing ligand (TRAIL). Other types of RBC damage, such as eryptotic damage, failed to induce necroptosis when combined with hCD59 crosslinking. This work sheds light on the requirements for this recently discovered PCD in RBCs and provides a clear picture of the biochemical mechanism of induction of RBC necroptosis.

Multi-walled carbon nanotubes (NM401) induce ROS-mediated HPRT mutations in Chinese hamster lung fibroblasts

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

Rubio, Laura; El Yamani, Naouale; Kazimirova, Alena

Although there is an important set of data showing potential genotoxic effects of nanomaterials (NMs) at the DNA (comet assay) and chromosome (micronucleus test) levels, few studies have been conducted to analyze their potential mutagenic effects at gene level. We have determined the ability of multi-walled carbon nanotubes (MWCNT, NM401), to induce mutations in the HPRT gene in Chinese hamster lung (V79) fibroblasts. NM401, characterized in the EU NanoGenotox project, were further studied within the EU Framework Programme Seven (FP7) project NANoREG. From the proliferation assay data we selected a dose-range of 0.12 to 12 µg/cm{sup 2} At these rangemore » we have been able to observe significant cellular uptake of MWCNT by using transmission electron microscopy (TEM), as well as a concentration-dependent induction of intracellular reactive oxygen species. In addition, a clear concentration-dependent increase in the induction of HPRT mutations was also observed. Data support a potential genotoxic/ carcinogenic risk associated with MWCNT exposure. - Highlights: • MWCNT were tested in V79 cells. • Cellular uptake of MWCNT was detected using TEM. • Intracellular ROS induction was observed after MWCNT exposure. • MWCNT induced a concentration-dependent increase of HPRT mutations.« less

The spread of Ras activity triggered by activation of a single dendritic spine.

PubMed

Harvey, Christopher D; Yasuda, Ryohei; Zhong, Haining; Svoboda, Karel

2008-07-04

In neurons, individual dendritic spines isolate N-methyl-d-aspartate (NMDA) receptor-mediated calcium ion (Ca2+) accumulations from the dendrite and other spines. However, the extent to which spines compartmentalize signaling events downstream of Ca2+ influx is not known. We combined two-photon fluorescence lifetime imaging with two-photon glutamate uncaging to image the activity of the small guanosine triphosphatase Ras after NMDA receptor activation at individual spines. Induction of long-term potentiation (LTP) triggered robust Ca2+-dependent Ras activation in single spines that decayed in approximately 5 minutes. Ras activity spread over approximately 10 micrometers of dendrite and invaded neighboring spines by diffusion. The spread of Ras-dependent signaling was necessary for the local regulation of the threshold for LTP induction. Thus, Ca2+-dependent synaptic signals can spread to couple multiple synapses on short stretches of dendrite.

Defect characterization by inductive heated thermography

NASA Astrophysics Data System (ADS)

Noethen, Matthias; Meyendorf, Norbert

2012-05-01

During inductive-thermographic inspection, an eddy current of high intensity is induced into the inspected material and the thermal response is detected by an infrared camera. Anomalies in the surface temperature during and after inductive heating correspond to inhomogeneities in the material. A finite element simulation of the surface crack detection process using active thermography with inductive heating has been developed. The simulation model is based on the finite element software ANSYS. The simulation tool was tested and used for investigations on steel components with different longitudinal orientated cracks, varying in shape, width and height. This paper focuses on surface connected longitudinal orientated cracks in austenitic steel. The results show that depending on the excitation frequency the temperature distribution of the material under test are different and a possible way to measure the depth of the crack will be discussed.

Automated identification of protein-ligand interaction features using Inductive Logic Programming: a hexose binding case study

PubMed Central

2012-01-01

Background There is a need for automated methods to learn general features of the interactions of a ligand class with its diverse set of protein receptors. An appropriate machine learning approach is Inductive Logic Programming (ILP), which automatically generates comprehensible rules in addition to prediction. The development of ILP systems which can learn rules of the complexity required for studies on protein structure remains a challenge. In this work we use a new ILP system, ProGolem, and demonstrate its performance on learning features of hexose-protein interactions. Results The rules induced by ProGolem detect interactions mediated by aromatics and by planar-polar residues, in addition to less common features such as the aromatic sandwich. The rules also reveal a previously unreported dependency for residues cys and leu. They also specify interactions involving aromatic and hydrogen bonding residues. This paper shows that Inductive Logic Programming implemented in ProGolem can derive rules giving structural features of protein/ligand interactions. Several of these rules are consistent with descriptions in the literature. Conclusions In addition to confirming literature results, ProGolem’s model has a 10-fold cross-validated predictive accuracy that is superior, at the 95% confidence level, to another ILP system previously used to study protein/hexose interactions and is comparable with state-of-the-art statistical learners. PMID:22783946

Clinical governance in the management of induction of labour.

PubMed

Zuberi, Nadeem Faiyaz; Siddiqui, Salva; Qureshi, Rahat Najam

2003-02-01

To determine whether dissemination of explicit guidelines, developed in consensus with stakeholders, for the processes of induction of labour (IOL), results in reduction of variability in clinical practice. A prospective behaviour modification interventional study. The study was conducted in the department of Obstetrics and Gynaecology at the Aga Khan University, Karachi, between January 1 and August 31, 2002. In a total of 142 conveniently sampled women, undergoing IOL, pre-identified quality assessment indicators were measured. After collection of data from initial 71-women (pre-intervention group) mutually agreed guidelines for clinical practice were disseminated, over a period of time, among consultants, residents and nurses. These indicators were again measured in subsequent 71 women (post-intervention group) to evaluate magnitude of residual non-conformities in these processes. Following behaviour modification interventions, nonconformities in consultants and residents-dependent processes like timely review of patients by consultants (72 vs 1.4%, p value <0.0001), documentation of indication for IOL (66.2 vs 16.9%, p value <0.0001), method of induction for IOL (56.3 vs 28.2%, p value 0.0001), and calculation of Bishop score before IOL (38.0 vs 4.2 %, p value <0.0001) were significantly reduced. Dissemination of explicit guidelines developed in consensus with stakeholders significantly reduces variability in clinical practice. Our model can be used for improving quality of care in other areas of obstetric health care.

Time-Dependent Effect of Encapsulating Alginate Hydrogel on Neurogenic Potential

PubMed Central

Razavi, Shahnaz; Khosravizadeh, Zahra; Bahramian, Hamid; Kazemi, Mohammad

2015-01-01

Objective Due to the restricted potential of neural stem cells for regeneration of central nervous system (CNS) after injury, providing an alternative source for neural stem cells is essential. Adipose derived stem cells (ADSCs) are multipotent cells with properties suitable for tissue engineering. In addition, alginate hydrogel is a biocompatible polysaccharide polymer that has been used to encapsulate many types of cells. The aim of this study was to assess the proliferation rate and level of expression of neural markers; NESTIN, glial fibrillary acidic protein (GFAP) and microtubule-associated protein 2 (MAP2) in encapsulated human ADSCs (hADSCs) 10 and14 days after neural induction. Materials and Methods In this experimental study, ADSCs isolated from human were cultured in neural induction media and seeded into alginate hydrogel. The rate of proliferation and differentiation of encapsulated cells were evaluated by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide (MTT) assay, immunocytoflourescent and realtime reverse transcriptase polymerase chain reaction (RT-PCR) analyzes 10 and 14 days after induction. Results The rate of proliferation of encapsulated cells was not significantly changed with time passage. The expression of NESTIN and GFAP significantly decreased on day 14 relative to day 10 (P<0.001) but MAP2 expression was increased. Conclusion Alginate hydrogel can promote the neural differentiation of encapsulated hADSCs with time passage. PMID:26199909

Metalloproteinase processing of HBEGF is a proximal event in the response of human aortic endothelial cells to oxidized phospholipids

PubMed Central

Lee, Sangderk; Springstead, James R.; Parks, Brian; Romanoski, Casey E.; Palvolgyi, Roland; Ho, Tiffany; Nguyen, Phuc; Lusis, Aldons J.; Berliner, Judith A.

2012-01-01

Objective Atherosclerosis is a chronic inflammatory disease initiated by monocyte recruitment and retention in the vessel wall. An important mediator of monocyte endothelial interaction is the chemokine IL-8. The oxidation products of phospholipids, including Ox-PAPC, accumulate in atherosclerotic lesions and strongly induce IL-8 in human aortic endothelial cells (HAECs). The goal of this study was to identify the proximal events leading to induction of IL-8 by Ox-PAPC in vascular endothelial cells. Methods and Results In a systems genetics analysis of HAECs isolated from 96 different human donors, we showed that HBEGF transcript levels are strongly correlated to IL-8 induction by Ox-PAPC. The silencing and overexpression of HBEGF in HAECs confirmed the role of HBEGF in regulating IL-8 expression. HBEGF has been shown to be stored in an inactive form and activation is dependent on processing by a dysintegrin and metalloproteinases (ADAM) to a form that can activate EGF receptor (EGFR). Ox-PAPC was shown to rapidly induce HBEGF processing and EGFR activation in HAECs. Using siRNA we identified three ADAMs that regulate IL-8 induction and directly demonstrated that Ox-PAPC increases ADAM activity in the cells by substrate cleavage assay. We provide evidence for one mechanism of Ox-PAPC activation of ADAM involving covalent binding of Ox-PAPC to cysteine on ADAM. Free thiol cysteine analogs showed inhibition of IL-8 induction by Ox-PAPC, and both a cysteine analog and a cell surface thiol blocker strongly inhibited ADAM activity induction by Ox-PAPC. Using microarray analyses, we determined that this ADAM pathway may regulate as much as 30% of genes induced by Ox-PAPC in HAECs. Conclusion This study is the first report demonstrating a role for the ADAM-HBEGF-EGFR axis in Ox-PAPC induction of IL-8 in HAECs. These studies highlight a role for specific ADAMs as initiators of Ox-PAPC action and provide evidence for a role of covalent interaction of Ox-PAPC in activation of ADAMs. PMID:22402363

Light-dependent quenching of chlorophyll fluorescence in pea chloroplasts induced by adenosine 5'-triphosphate.

PubMed

Horton, P; Black, M T

1981-03-12

Addition of ATP to chloroplasts causes a reversible 25-30% decrease in chlorophyll fluorescence. This quenching is light-dependent, uncoupler insensitive but inhibited by DCMU and electron acceptors and has a half-time of 3 minutes. Electron donors to Photosystem I can not overcome the inhibitory effect of DCMU, suggesting that light activation depends on the reduced state of plastoquinone. Fluorescence emission spectra recorded at -196 degrees C indicate that ATP treatment increases the amount of excitation energy transferred to Photosystem I. Examination of fluorescence induction curves indicate that ATP treatment decreases both the initial (F0) and variable (Fv) fluorescence such that the ratio of Fv to the maximum (Fm) yield is unchanged. The initial sigmoidal phase of induction is slowed down by ATP treatment and is quenched 3-fold more than the exponential slow phase, the rate of which is unchanged. A plot of Fv against area above the induction curve was identical plus or minus ATP. Thus ATP treatment can alter quantal distribution between Photosystems II and I without altering Photosystem II-Photosystem II interaction. The effect of ATP strongly resembles in its properties the phosphorylation of the light-harvesting complex by a light activated, ATP-dependent protein kinase found in chloroplast membranes and could be the basis of physiological mechanisms which contribute to slow fluorescence quenching in vivo and regulate excitation energy distribution between Photosystem I and II. It is suggested that the sensor for this regulation is the redox state of plastoquinone.

A prospective pilot study of Dilapan-S compared with Propess for induction of labour at 41+ weeks in nulliparous pregnancy.

PubMed

Crosby, David A; O'Reilly, Claire; McHale, Helen; McAuliffe, Fionnuala M; Mahony, Rhona

2017-12-21

The incidence of labour induction has risen worldwide over the past decade, and this may contribute to the rising caesarean delivery rate. The mechanisms for induction of labour are generally divided into two categories: mechanical and pharmacological. The objective of this study was to determine if mechanical induction with Dilapan-S is an acceptable, safe method of induction of labour in post-dates uncomplicated nulliparous pregnancy. This was a single-centre prospective observational pilot study trial. Fifty-two low-risk nulliparous women with an unfavourable cervix, scheduled for induction of labour for post-dates ≥ 41 weeks gestation, were offered induction of labour with Dilapan-S or Propess from May 2016 until November 2016. The primary outcomes measured were compliance to study protocol and maternal (infection, hyperstimulation) and neonatal outcomes (Apgar score at birth). The secondary outcome measures included change in Bishop's score and caesarean delivery rate. Compliance to study protocol was 25/26 (96%); it was possible to insert Dilapan-S in all but one woman. There were no differences in maternal and neonatal primary outcomes between the groups. There were no cases in either arm of hyperstimulation with either induction method. No difference between the groups was noted in the caesarean delivery rate nor in the mean change in Bishop's score. Dilapan-S is an acceptable, safe form of induction of labour in post-dates uncomplicated nulliparous pregnancy. No cases of hyperstimulation were found, and therefore, Dilapan-S may be a suitable option for outpatient induction of labour in low-risk post-dates nulliparas.

Characterization of titanium dioxide nanoparticles in food products: analytical methods to define nanoparticles.

PubMed

Peters, Ruud J B; van Bemmel, Greet; Herrera-Rivera, Zahira; Helsper, Hans P F G; Marvin, Hans J P; Weigel, Stefan; Tromp, Peter C; Oomen, Agnes G; Rietveld, Anton G; Bouwmeester, Hans

2014-07-09

Titanium dioxide (TiO2) is a common food additive used to enhance the white color, brightness, and sometimes flavor of a variety of food products. In this study 7 food grade TiO2 materials (E171), 24 food products, and 3 personal care products were investigated for their TiO2 content and the number-based size distribution of TiO2 particles present in these products. Three principally different methods have been used to determine the number-based size distribution of TiO2 particles: electron microscopy, asymmetric flow field-flow fractionation combined with inductively coupled mass spectrometry, and single-particle inductively coupled mass spectrometry. The results show that all E171 materials have similar size distributions with primary particle sizes in the range of 60-300 nm. Depending on the analytical method used, 10-15% of the particles in these materials had sizes below 100 nm. In 24 of the 27 foods and personal care products detectable amounts of titanium were found ranging from 0.02 to 9.0 mg TiO2/g product. The number-based size distributions for TiO2 particles in the food and personal care products showed that 5-10% of the particles in these products had sizes below 100 nm, comparable to that found in the E171 materials. Comparable size distributions were found using the three principally different analytical methods. Although the applied methods are considered state of the art, they showed practical size limits for TiO2 particles in the range of 20-50 nm, which may introduce a significant bias in the size distribution because particles <20 nm are excluded. This shows the inability of current state of the art methods to support the European Union recommendation for the definition of nanomaterials.

Formation of oral and pharyngeal dentition in teleosts depends on differential recruitment of retinoic acid signaling

PubMed Central

Gibert, Yann; Bernard, Laure; Debiais-Thibaud, Melanie; Bourrat, Franck; Joly, Jean-Stephane; Pottin, Karen; Meyer, Axel; Retaux, Sylvie; Stock, David W.; Jackman, William R.; Seritrakul, Pawat; Begemann, Gerrit; Laudet, Vincent

2010-01-01

One of the goals of evolutionary developmental biology is to link specific adaptations to changes in developmental pathways. The dentition of cypriniform fishes, which in contrast to many other teleost fish species possess pharyngeal teeth but lack oral teeth, provides a suitable model to study the development of feeding adaptations. Here, we have examined the involvement of retinoic acid (RA) in tooth development and show that RA is specifically required to induce the pharyngeal tooth developmental program in zebrafish. Perturbation of RA signaling at this stage abolished tooth induction without affecting the development of tooth-associated ceratobranchial bones. We show that this inductive event is dependent on RA synthesis from aldh1a2 in the ventral posterior pharynx. Fibroblast growth factor (FGF) signaling has been shown to be critical for tooth induction in zebrafish, and its loss has been associated with oral tooth loss in cypriniform fishes. Pharmacological treatments targeting the RA and FGF pathways revealed that both pathways act independently during tooth induction. In contrast, we find that in Mexican tetra and medaka, species that also possess oral teeth, both oral and pharyngeal teeth are induced independently of RA. Our analyses suggest an evolutionary scenario in which the gene network controlling tooth development obtained RA dependency in the lineage leading to the cypriniforms. The loss of pharyngeal teeth in this group was cancelled out through a shift in aldh1a2 expression, while oral teeth might have been lost ultimately due to deficient RA signaling in the oral cavity.—Gibert, Y., Bernard, L., Debiais-Thibaud, M., Bourrat, F., Joly, J.-S., Pottin, K., Meyer, A., Retaux, S., Stock, D. W., Jackman, W. R., Seritrakul, P., Begemann, G., Laudet, V. Formation of oral and pharyngeal dentition in teleosts depends on differential recruitment of retinoic acid signaling. PMID:20445074

Empirical Analysis and Refinement of Expert System Knowledge Bases

DTIC Science & Technology

1990-03-31

the number of hidden units and the error rates is listed in Figure 6. 3.3. Cancer Data A data qet for eva!ukting th.- Frognosis of breast cancer ...Alternative Rule Induction Methods A data set for evaluating the prognosis of breast cancer recurrence was analyzed by Michalski’s AQI5 rule induction program...AQ15 7 2 32% PVM 2 1 23% Figure 6-3: Comparative Summa-y for AQI5 and PVM on Breast Cancer Data 6.2.2. Alternative Decision Tree Induction Methods

Apparatus and method for characterizing conductivity of materials

DOEpatents

Doss, J.D.

1988-04-13

Apparatus and method for noncontact, radio-frequency shielding current characterization of materials. Self- or mutual inductance changes in one or more inductive elements, respectively, occur when materials capable of supporting shielding currents are placed in proximity thereto, or undergo change in resistivity while in place. Such changes can be observed by incorporating the inductor(s) in a resonant circuit and determining the frequency of oscillation or by measuring the voltage induced on a coupled inductive element. The present invention is useful for determining the critical temperature and superconducting transition width for superconducting samples. 8 figs.

The Impact of a Multilevel Intervention on Special Education Induction Teacher Retention Indicators

ERIC Educational Resources Information Center

Imel, Breck

2012-01-01

This mixed methods action research study explores the impact of a multilevel intervention on retention indicators of special education induction teachers and the leadership capacities of the special education induction coaches and coordinator. The purpose of this investigation was to understand the impact of developing and implementing an action…

Beginning Teachers' Perception of Their Induction into the Teaching Profession

ERIC Educational Resources Information Center

Kidd, Lynda; Brown, Natalie; Fitzallen, Noleine

2015-01-01

Beginning teachers' induction into the teaching profession needs to be personally and professionally fulfilling, which is often not the case. The main objective of this mixed method study was to gain a deeper understanding of beginning teachers' experiences and the perceptions of their induction into the teaching profession and the support they…

Examining the Effects of New Teacher Induction

ERIC Educational Resources Information Center

Wechsler, Marjorie E.; Caspary, Kyra; Humphrey, Daniel C.; Matsko, Kavita Kapadia

2012-01-01

The objective of this research is to explore comprehensively the effect of induction on new teachers. Through a mixed-method design, the authors examine both the inputs of induction (i.e., the types of support provided for new teachers, its content, and frequency) and a variety of outcomes (i.e., teacher efficacy, teacher-reported growth, teacher…

Teaching Mathematical Induction: An Alternative Approach.

ERIC Educational Resources Information Center

Allen, Lucas G.

2001-01-01

Describes experience using a new approach to teaching induction that was developed by the Mathematical Methods in High School Project. The basic idea behind the new approach is to use induction to prove that two formulas, one in recursive form and the other in a closed or explicit form, will always agree for whole numbers. (KHR)

Learning predictive models that use pattern discovery--a bootstrap evaluative approach applied in organ functioning sequences.

PubMed

Toma, Tudor; Bosman, Robert-Jan; Siebes, Arno; Peek, Niels; Abu-Hanna, Ameen

2010-08-01

An important problem in the Intensive Care is how to predict on a given day of stay the eventual hospital mortality for a specific patient. A recent approach to solve this problem suggested the use of frequent temporal sequences (FTSs) as predictors. Methods following this approach were evaluated in the past by inducing a model from a training set and validating the prognostic performance on an independent test set. Although this evaluative approach addresses the validity of the specific models induced in an experiment, it falls short of evaluating the inductive method itself. To achieve this, one must account for the inherent sources of variation in the experimental design. The main aim of this work is to demonstrate a procedure based on bootstrapping, specifically the .632 bootstrap procedure, for evaluating inductive methods that discover patterns, such as FTSs. A second aim is to apply this approach to find out whether a recently suggested inductive method that discovers FTSs of organ functioning status is superior over a traditional method that does not use temporal sequences when compared on each successive day of stay at the Intensive Care Unit. The use of bootstrapping with logistic regression using pre-specified covariates is known in the statistical literature. Using inductive methods of prognostic models based on temporal sequence discovery within the bootstrap procedure is however novel at least in predictive models in the Intensive Care. Our results of applying the bootstrap-based evaluative procedure demonstrate the superiority of the FTS-based inductive method over the traditional method in terms of discrimination as well as accuracy. In addition we illustrate the insights gained by the analyst into the discovered FTSs from the bootstrap samples. Copyright 2010 Elsevier Inc. All rights reserved.

Theoretical and Experimental Estimations of Volumetric Inductive Phase Shift in Breast Cancer Tissue

NASA Astrophysics Data System (ADS)

González, C. A.; Lozano, L. M.; Uscanga, M. C.; Silva, J. G.; Polo, S. M.

2013-04-01

Impedance measurements based on magnetic induction for breast cancer detection has been proposed in some studies. This study evaluates theoretical and experimentally the use of a non-invasive technique based on magnetic induction for detection of patho-physiological conditions in breast cancer tissue associated to its volumetric electrical conductivity changes through inductive phase shift measurements. An induction coils-breast 3D pixel model was designed and tested. The model involves two circular coils coaxially centered and a human breast volume centrally placed with respect to the coils. A time-harmonic numerical simulation study addressed the effects of frequency-dependent electrical properties of tumoral tissue on the volumetric inductive phase shift of the breast model measured with the circular coils as inductor and sensor elements. Experimentally; five female volunteer patients with infiltrating ductal carcinoma previously diagnosed by the radiology and oncology departments of the Specialty Clinic for Women of the Mexican Army were measured by an experimental inductive spectrometer and the use of an ergonomic inductor-sensor coil designed to estimate the volumetric inductive phase shift in human breast tissue. Theoretical and experimental inductive phase shift estimations were developed at four frequencies: 0.01, 0.1, 1 and 10 MHz. The theoretical estimations were qualitatively in agreement with the experimental findings. Important increments in volumetric inductive phase shift measurements were evident at 0.01MHz in theoretical and experimental observations. The results suggest that the tested technique has the potential to detect pathological conditions in breast tissue associated to cancer by non-invasive monitoring. Further complementary studies are warranted to confirm the observations.

Functional recombinant protein is present in the pre-induction phases of Pichia pastoris cultures when grown in bioreactors, but not shake-flasks.

PubMed

Bawa, Zharain; Routledge, Sarah J; Jamshad, Mohammed; Clare, Michelle; Sarkar, Debasmita; Dickerson, Ian; Ganzlin, Markus; Poyner, David R; Bill, Roslyn M

2014-09-04

Pichia pastoris is a widely-used host for recombinant protein production; expression is typically driven by methanol-inducible alcohol oxidase (AOX) promoters. Recently this system has become an important source of recombinant G protein-coupled receptors (GPCRs) for structural biology and drug discovery. The influence of diverse culture parameters (such as pH, dissolved oxygen concentration, medium composition, antifoam concentration and culture temperature) on productivity has been investigated for a wide range of recombinant proteins in P. pastoris. In contrast, the impact of the pre-induction phases on yield has not been as closely studied. In this study, we examined the pre-induction phases of P. pastoris bioreactor cultivations producing three different recombinant proteins: the GPCR, human A(2a) adenosine receptor (hA(2a)R), green fluorescent protein (GFP) and human calcitonin gene-related peptide receptor component protein (as a GFP fusion protein; hCGRP-RCP-GFP). Functional hA(2a)R was detected in the pre-induction phases of a 1 L bioreactor cultivation of glycerol-grown P. pastoris. In a separate experiment, a glycerol-grown P. pastoris strain secreted soluble GFP prior to methanol addition. When glucose, which has been shown to repress AOX expression, was the pre-induction carbon source, hA(2a)R and GFP were still produced in the pre-induction phases. Both hA(2a)R and GFP were also produced in methanol-free cultivations; functional protein yields were maintained or increased after depletion of the carbon source. Analysis of the pre-induction phases of 10 L pilot scale cultivations also demonstrated that pre-induction yields were at least maintained after methanol induction, even in the presence of cytotoxic concentrations of methanol. Additional bioreactor data for hCGRP-RCP-GFP and shake-flask data for GFP, horseradish peroxidase (HRP), the human tetraspanins hCD81 and CD82, and the tight-junction protein human claudin-1, demonstrated that bioreactor but not shake-flask cultivations exhibit recombinant protein production in the pre-induction phases of P. pastoris cultures. The production of recombinant hA(2a)R, GFP and hCGRP-RCP-GFP can be detected in bioreactor cultivations prior to methanol induction, while this is not the case for shake-flask cultivations of GFP, HRP, hCD81, hCD82 and human claudin-1. This confirms earlier suggestions of leaky expression from AOX promoters, which we report here for both glycerol- and glucose-grown cells in bioreactor cultivations. These findings suggest that the productivity of AOX-dependent bioprocesses is not solely dependent on induction by methanol. We conclude that in order to maximize total yields, pre-induction phase cultivation conditions should be optimized, and that increased specific productivity may result in decreased biomass yields.

Assessment of the Role of MAP Kinase in Mediating Activity-Dependent Transcriptional Activation of the Immediate Early Gene "Arc/Arg3.1" in the Dentate Gyrus in Vivo

ERIC Educational Resources Information Center

Chotiner, Jennifer K.; Nielson, Jessica; Farris, Shannon; Lewandowski, Gail; Huang, Fen; Banos, Karla; de Leon, Ray; Steward, Oswald

2010-01-01

Different physiological and behavioral events activate transcription of "Arc/Arg3.1" in neurons in vivo, but the signal transduction pathways that mediate induction in particular situations remain to be defined. Here, we explore the relationships between induction of "Arc/Arg3.1" transcription in dentate granule cells in vivo and activation of…

Comparative evaluation of power factor impovement techniques for squirrel cage induction motors

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

Spee, R.; Wallace, A.K.

1992-04-01

This paper describes the results obtained from a series of tests of relatively simple methods of improving the power factor of squirrel-cage induction motors. The methods, which are evaluated under controlled laboratory conditions for a 10-hp, high-efficiency motor, include terminal voltage reduction; terminal static capacitors; and a floating'' winding with static capacitors. The test results are compared with equivalent circuit model predictions that are then used to identify optimum conditions for each of the power factor improvement techniques compared with the basic induction motor. Finally, the relative economic value, and the implications of component failures, of the three methods aremore » discussed.« less

Method for reducing peak phase current and decreasing staring time for an internal combustion engine having an induction machine

DOEpatents

Amey, David L.; Degner, Michael W.

2002-01-01

A method for reducing the starting time and reducing the peak phase currents for an internal combustion engine that is started using an induction machine starter/alternator. The starting time is reduced by pre-fluxing the induction machine and the peak phase currents are reduced by reducing the flux current command after a predetermined period of time has elapsed and concurrent to the application of the torque current command. The method of the present invention also provides a strategy for anticipating the start command for an internal combustion engine and determines a start strategy based on the start command and the operating state of the internal combustion engine.

Inter- and Intra-Dimensional Dependencies in Implicit Phonotactic Learning

ERIC Educational Resources Information Center

Moreton, Elliott

2012-01-01

Is phonological learning subject to the same inductive biases as learning in other domains? Previous studies of non-linguistic learning found that intra-dimensional dependencies (between two instances of the same feature) were learned more easily than inter-dimensional ones. This study compares implicit learning of intra- and inter-dimensional…

A Global Genomic Screening Strategy Reveals Diverse Activators of Constitutive Activated Receptor (CAR)

EPA Science Inventory

A comprehensive survey of conditions that activate CAR in the mouse liver has not been carried out but would be useful in understanding their impact on CAR-dependent liver tumor induction. A gene signature dependent on CAR activation was identified by comparing the transcript pr...

The Determination of Vitamin D-Dependent Calcium Binding Protein in Chick Intesting: An Undergraduate Biochemistry Laboratory Experiment.

ERIC Educational Resources Information Center

Lessard, George M.

1980-01-01

Described is an experiment used in an undergraduate biochemistry laboratory involving inducing rickets in chicks and correlating the disease to a reduction in vitamin D-dependent calcium binding protein. Techniques involved are hormone induction, protein isolation, and radioisotope methodology. (Author/DS)

Redefining the magic square on numerical characters

NASA Astrophysics Data System (ADS)

Nasution, M. K. M.; Sawaluddin

2018-02-01

As a number system, the magic square is different from the others. Characteristic depends not only on size but also depends on numerical character in computation. This paper has redefined the term of magic square formally, by exposing the inductive general characteristics of cases to numerical ordering of numbers.

The Exclusive Induction of Extinction Is Gated by BDNF

ERIC Educational Resources Information Center

Kirtley, Anne; Thomas, Kerrie L.

2010-01-01

We have previously reported that the reconsolidation and extinction of hippocampal-dependent contextual fear memory can be initiated by a single context conditioned stimulus (CS) presentation of either short or long duration, and that both processes require protein synthesis in this brain region. Furthermore, reconsolidation depends on Zif268…

Investigating the procedural variables that determine whether rats will display negative anticipatory contrast or positive induction.

PubMed

Weatherly, Jeffrey N; Nurnberger, Jeri T; Hanson, Brent C

2005-08-31

Previous studies have demonstrated that consumption of a low-valued food substance may decrease if access to a high-valued substance will soon be available (negative anticipatory contrast). Research has also demonstrated that responding for a low-valued reinforcer may increase if responding for a high-valued reinforcer will soon be possible (positive induction). The present experiment employed rats to respond in a procedure similar to that typically used to produce negative anticipatory contrast. The goal was to determine what factors contribute to when a contrast or an induction effect will occur. Based on previous research, the influence of auditory cues, temporal delays, food deprivation, and location of substance delivery were investigated. Auditory cues and temporal delays did little to influence whether subjects increased or decreased their consumption of 1% sucrose when access to 32% sucrose was upcoming. The appearance of contrast or induction was related to level of deprivation, with deprivation promoting induction. Which effect occurred also depended on whether subjects consumed the two substances from one spout in one location (induction) or from two different spouts in two different locations (contrast). The present results help identify the procedural link(s) between these two effects. They also provide insight to why positive induction may occur (i.e., higher-order place conditioning).

Induction as Knowledge Integration

NASA Technical Reports Server (NTRS)

Smith, Benjamin D.; Rosenbloom, Paul S.

1996-01-01

Two key issues for induction algorithms are the accuracy of the learned hypothesis and the computational resources consumed in inducing that hypothesis. One of the most promising ways to improve performance along both dimensions is to make use of additional knowledge. Multi-strategy learning algorithms tackle this problem by employing several strategies for handling different kinds of knowledge in different ways. However, integrating knowledge into an induction algorithm can be difficult when the new knowledge differs significantly from the knowledge the algorithm already uses. In many cases the algorithm must be rewritten. This paper presents Knowledge Integration framework for Induction (KII), a KII, that provides a uniform mechanism for integrating knowledge into induction. In theory, arbitrary knowledge can be integrated with this mechanism, but in practice the knowledge representation language determines both the knowledge that can be integrated, and the costs of integration and induction. By instantiating KII with various set representations, algorithms can be generated at different trade-off points along these dimensions. One instantiation of KII, called RS-KII, is presented that can implement hybrid induction algorithms, depending on which knowledge it utilizes. RS-KII is demonstrated to implement AQ-11, as well as a hybrid algorithm that utilizes a domain theory and noisy examples. Other algorithms are also possible.

Antimicrobial peptide gene induction, involvement of Toll and IMD pathways and defense against bacteria in the red flour beetle, Tribolium castaneum.

PubMed

Yokoi, Kakeru; Koyama, Hiroaki; Minakuchi, Chieka; Tanaka, Toshiharu; Miura, Ken

2012-01-01

Using Tribolium castaneum, we quantitatively investigated the induction of nine antimicrobial peptide (AMP) genes by live gram-negative bacteria (Escherichia coli and Enterobacter cloacae), gram-positive bacteria (Micrococcus luteus and Bacillus subtilis) and the budding yeast (Saccharomyces cerevisiae). Then, five representative AMP genes were selected, and the involvement of the Toll and IMD pathways in their induction by E. coli, M. luteus and S. cerevisiae was examined by utilizing RNA interference of either MyD88 or IMD. Results indicated: Robust and acute induction of three genes by the two bacterial species was mediated mainly by the IMD pathway; slow and sustained induction of one gene by the two bacteria was mediated mainly by the Toll pathway; induction of the remaining one gene by the two bacteria was mediated by both pathways; induction of the five genes by the yeast was mediated by the Toll and/or IMD pathways depending on respective genes. These results suggest that more promiscuous activation and usage of the two pathways may occur in T. castaneum than in Drosophila melanogaster. In addition, the IMD pathway was revealed to dominantly contribute to defense against two bacterial species, gram-negative E. cloacae and gram-positive B. subtilis that possesses DAP-type peptidoglycan.

p21 induction plays a dual role in anti-cancer activity of ursolic acid

PubMed Central

Zhang, Xudong; Song, Xinhua; Yin, Shutao; Zhao, Chong; Fan, Lihong

2015-01-01

Previous studies have shown that induction of G1 arrest and apoptosis by ursolic acid is associated with up-regulation of cyclin-dependent kinase inhibitor (CDKI) protein p21 in multiple types of cancer cells. However, the functional role of p21 induction in G1 cell cycle arrest and apoptosis, and the mechanisms of p21 induction by ursolic acid have not been critically addressed. In the current study, we demonstrated that p21 played a mediator role in G1 cell cycle arrest by ursolic acid, whereas p21-mediated up-regulation of Mcl-1 compromised apoptotic effect of ursolic acid. These results suggest that p21 induction plays a dual role in the anti-cancer activity of ursolic acid in terms of cell cycle and apoptosis regulation. p21 induction by ursolic acid was attributed to p53 transcriptional activation. Moreover, we found that ursolic acid was able to inhibit murine double minute-2 protein (MDM2) and T-LAK cell-originated protein kinase (TOPK), the two negative regulator of p53, which in turn contributed to ursolic acid-induced p53 activation. Our findings provided novel insights into understanding of the mechanisms involved in cell cycle arrest and apoptosis induction in response to ursolic acid exposure. PMID:26582056

STING-Dependent Interferon-λ1 Induction in HT29 Cells, a Human Colorectal Cancer Cell Line, After Gamma-Radiation.

PubMed

Chen, Jianzhou; Markelc, Bostjan; Kaeppler, Jakob; Ogundipe, Vivian M L; Cao, Yunhong; McKenna, W Gillies; Muschel, Ruth J

2018-05-01

To investigate the induction of type III interferons (IFNs) in human cancer cells by gamma-rays. Type III IFN expression in human cancer cell lines after gamma-ray irradiation in vitro was assessed by reverse transcription-quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. Signaling pathways mediating type III IFN induction were examined by a variety of means, including immunoblotting, flow cytometry, confocal imaging, and reverse transcription-quantitative polymerase chain reaction. Key mediators in these pathways were further explored and validated using gene CRISPR knockout or short hairpin RNA knockdown. Exposure to gamma-rays directly induced type III IFNs (mainly IFNL1) in human cancer cell lines in dose- and time-dependent fashions. The induction of IFNL1 was primarily mediated by the cytosolic DNA sensors-STING-TBK1-IRF1 signaling axis, with a lesser contribution from the nuclear factor kappa b signaling in HT29 cells. In addition, type III IFN signaling through its receptors serves as a positive feedback loop, further enhancing IFN expression via up-regulation of the kinases in the STING-TBK1 signaling axis. Our results suggest that IFNL1 can be up-regulated in human cancer cell lines after gamma-ray treatment. In HT29 cells this induction occurs via the STING pathway, adding another layer of complexity to the understanding of radiation-induced antitumor immunity, and may provide novel insights into IFN-based cancer treatment. Copyright © 2018 Elsevier Inc. All rights reserved.

Autophagy induced by AXL receptor tyrosine kinase alleviates acute liver injury via inhibition of NLRP3 inflammasome activation in mice.

PubMed

Han, Jihye; Bae, Joonbeom; Choi, Chang-Yong; Choi, Sang-Pil; Kang, Hyung-Sik; Jo, Eun-Kyeong; Park, Jongsun; Lee, Young Sik; Moon, Hyun-Seuk; Park, Chung-Gyu; Lee, Myung-Shik; Chun, Taehoon

2016-12-01

Severe hepatic inflammation is a common cause of acute or chronic liver disease. Macrophages are one of the key mediators which regulate the progress of hepatic inflammation. Increasing evidence shows that the TAM (TYRO3, AXL and MERTK) family of RTKs (receptor tyrosine kinases), which is expressed in macrophages, alleviates inflammatory responses through a negative feedback loop. However, the functional contribution of each TAM family member to the progression of hepatic inflammation remains elusive. In this study, we explore the role of individual TAM family proteins during autophagy induction and evaluate their contribution to hepatic inflammation. Among the TAM family of RTKs, AXL (AXL receptor tyrosine kinase) only induces autophagy in macrophages after interaction with its ligand, GAS6 (growth arrest specific 6). Based on our results, autophosphorylation of 2 tyrosine residues (Tyr815 and Tyr860) in the cytoplasmic domain of AXL in mice is required for autophagy induction and AXL-mediated autophagy induction is dependent on MAPK (mitogen-activated protein kinase)14 activity. Furthermore, induction of AXL-mediated autophagy prevents CASP1 (caspase 1)-dependent IL1B (interleukin 1, β) and IL18 (interleukin 18) maturation by inhibiting NLRP3 (NLR family, pyrin domain containing 3) inflammasome activation. In agreement with these observations, axl -/- mice show more severe symptoms than do wild-type (Axl +/+ ) mice following acute hepatic injury induced by administration of lipopolysaccharide (LPS) or carbon tetrachloride (CCl 4 ). Hence, GAS6-AXL signaling-mediated autophagy induction in murine macrophages ameliorates hepatic inflammatory responses by inhibiting NLRP3 inflammasome activation.

The Enhancement of Phototropin-Induced Phototropic Curvature in Arabidopsis Occurs via a Photoreversible Phytochrome A-Dependent Modulation of Auxin Responsiveness1

PubMed Central

Stowe-Evans, Emily L.; Luesse, Darron R.; Liscum, Emmanuel

2001-01-01

The induction of phototropism in etiolated (dark-grown) seedlings exposed to an unidirectional pulse or extended irradiation with low fluence rate blue light (BL) requires the action of the phototropin (nph1) BL receptor. Although cryptochromes and phytochromes are not required for phototropic induction, these photoreceptors do modulate the magnitude of curvature resulting from phototropin activation. Modulatory increases in the magnitude of phototropic curvature have been termed “enhancement.” Here, we show that phototropic enhancement is primarily a phytochrome A (phyA)-dependent red/far-red-reversible low fluence response. This phyA-dependent response is genetically separable from the basal phototropin-dependent response, as demonstrated by its retention under extended irradiation conditions in the nph4 mutant background, which normally lacks the basal BL-induced response. It is interesting that the nph4 mutants fail to exhibit the basal phototropin-dependent and phyA-dependent enhancement responses under limiting light conditions. Given that NPH4 encodes a transcriptional activator, auxin response factor 7 (ARF7), we hypothesize that the ultimate target(s) of phyA action during the phototropic enhancement response is a rate-limiting ARF-containing transcriptional complex in which the constituent ARFs can vary in identity or activity depending upon the irradiation condition. PMID:11402210

Effects of Physical Models and Simulations to Understand Daily Life Applications of Electromagnetic Induction

ERIC Educational Resources Information Center

Tural, Güner; Tarakçi, Demet

2017-01-01

Background: One of the topics students have difficulties in understanding is electromagnetic induction. Active learning methods instead of traditional learning method may be able to help facilitate students' understanding such topics more effectively. Purpose: The study investigated the effectiveness of physical models and simulations on students'…

Particle-in-cell simulations of electron beam control using an inductive current divider

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

Swanekamp, S. B.; Angus, J. R.; Cooperstein, G.

2015-11-15

Kinetic, time-dependent, electromagnetic, particle-in-cell simulations of the inductive current divider are presented. The inductive current divider is a passive method for controlling the trajectory of an intense, hollow electron beam using a vacuum structure that inductively splits the beam's return current. The current divider concept was proposed and studied theoretically in a previous publication [Swanekamp et al., Phys. Plasmas 22, 023107 (2015)]. A central post carries a portion of the return current (I{sub 1}), while the outer conductor carries the remainder (I{sub 2}) with the injected beam current given by I{sub b} = I{sub 1} + I{sub 2}. The simulations are in agreement withmore » the theory which predicts that the total force on the beam trajectory is proportional to (I{sub 2}−I{sub 1}) and the force on the beam envelope is proportional to I{sub b}. Independent control over both the current density and the beam angle at the target is possible by choosing the appropriate current-divider geometry. The root-mean-square (RMS) beam emittance (ε{sub RMS}) varies as the beam propagates through the current divider to the target. For applications where control of the beam trajectory is desired and the current density at the target is similar to the current density at the entrance foil, there is a modest 20% increase in ε{sub RMS} at the target. For other applications where the beam is pinched to a current density ∼5 times larger at the target, ε{sub RMS} is 2–3 times larger at the target.« less

Effect of Different Agrobacterium rhizogenes Strains on Hairy Root Induction and Phenylpropanoid Biosynthesis in Tartary Buckwheat (Fagopyrum tataricum Gaertn)

PubMed Central

Thwe, Aye; Valan Arasu, Mariadhas; Li, Xiaohua; Park, Chang Ha; Kim, Sun Ju; Al-Dhabi, Naif Abdullah; Park, Sang Un

2016-01-01

The development of an efficient protocol for successful hairy root induction by Agrobacterium rhizogenes is the key step toward an in vitro culturing method for the mass production of secondary metabolites. The selection of an effective Agrobacterium strain for the production of hairy roots is highly plant species dependent and must be determined empirically. Therefore, our goal was to investigate the transformation efficiency of different A. rhizogenes strains for the induction of transgenic hairy roots in Fagopyrum tataricum ‘Hokkai T10’ cultivar; to determine the expression levels of the polypropanoid biosynthetic pathway genes, such as ftpAL, FtC4H, Ft4CL, FrCHS, FrCH1, FrF3H, FtFLS1, FtFLS2, FtF3, H1, FtF3′H2, FtANS, and FtDFR; and to quantify the in vitro synthesis of phenolic compounds and anthocyanins. Among different strains, R1000 was the most promising candidate for hairy root stimulation because it induced the highest growth rate, root number, root length, transformation efficiency, and total anthocyanin and rutin content. The R1000, 15834, and A4 strains provided higher transcript levels for most metabolic pathway genes for the synthesis of rutin (22.31, 15.48, and 13.04 μg/mg DW, respectively), cyanidin 3-O-glucoside (800, 750, and 650 μg/g DW, respectively), and cyanidin 3-O-rutinoside (2410, 1530, and 1170 μg/g DW, respectively). A suitable A. rhizogenes strain could play a vital role in the fast growth of the bulk amount of hairy roots and secondary metabolites. Overall, R1000 was the most promising strain for hairy root induction in buckwheat. PMID:27014239

Induction of an adaptive response in human blood lymphocytes exposed to radiofrequency fields: influence of the universal mobile telecommunication system (UMTS) signal and the specific absorption rate.

PubMed

Zeni, Olga; Sannino, Anna; Romeo, Stefania; Massa, Rita; Sarti, Maurizio; Reddy, Abishek B; Prihoda, Thomas J; Vijayalaxmi; Scarfì, Maria Rosaria

2012-08-30

The induction of an adaptive response (AR) was examined in human peripheral blood lymphocytes exposed to non-ionizing radiofrequency fields (RF). Cells from nine healthy human volunteers were stimulated for 24h with phytohaemagglutinin and then exposed for 20h to an adaptive dose (AD) of a 1950MHz RF UMTS (universal mobile telecommunication system) signal used for mobile communications, at different specific absorption rates (SAR) of 1.25, 0.6, 0.3, and 0.15W/kg. This was followed by treatment of the cells at 48h with a challenge dose (CD) of 100ng/ml mitomycin C (MMC). Lymphocytes were collected at the end of the 72h total culture period. The cytokinesis-block method was used to record the frequency of micronuclei (MN) as genotoxicity end-point. When lymphocytes from six donors were pre-exposed to RF at 0.3W/kg SAR and then treated with MMC, these cells showed a significant reduction in the frequency of MN, compared with the cells treated with MMC alone; this result is indicative of induction of AR. The results from our earlier study indicated that lymphocytes that were stimulated for 24h, exposed for 20h to a 900MHz RF GSM (global system for mobile communication) signal at 1.25W/kg SAR and then treated with 100ng/ml MMC, also exhibited AR. These overall data suggest that the induction of AR depends on RF frequency, type of the signal and SAR. Further characterization of RF-induced AR is in progress. Copyright © 2012 Elsevier B.V. All rights reserved.

Citrus nobiletin suppresses inducible nitric oxide synthase gene expression in interleukin-1β-treated hepatocytes

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

Yoshigai, Emi; Ritsumeikan Global Innovation Research Organization; Machida, Toru

Highlights: •Nobiletin is a polymethoxylated flavone that is abundant in citrus peels. •Nobiletin is a major constituent of the Citrus unshiu peel extract. •Nobiletin suppresses induction of NO and reduces iNOS expression in hepatocytes. •Nobiletin reduces the iNOS promoter activity and the DNA-binding activity of NF-κB. -- Abstract: Background: Nobiletin is a polymethoxylated flavone that is abundant in the peels of citrus fruits, such as Citrus unshiu (Satsuma mandarin) and Citrus sinensis. The dried peels of C. unshiu (chinpi) have been included in several formulae of Japanese Kampo medicines. Nobiletin may suppress the induction of inducible nitric oxide synthase (iNOS),more » which synthesizes the inflammatory mediator nitric oxide (NO) in hepatocytes. Methods: A C. unshiu peel (CUP) extract was prepared. Primary cultured rat hepatocytes were treated with the CUP extract or nobiletin in the presence of interleukin 1β (IL-1β), which induces iNOS expression. NO production and iNOS gene expression were analyzed. Results: High-performance liquid chromatography analyses revealed that the nobiletin content in the CUP extract was 0.14%. Nobiletin dose-dependently reduced the NO levels and decreased iNOS expression at the protein, mRNA and antisense transcript levels. Flavone, which does not contain any methoxy groups, also suppressed iNOS induction. Nobiletin reduced the transcriptional activity of iNOS promoter-luciferase constructs and the DNA-binding activity of nuclear factor κB (NF-κB) in the nuclei. Conclusions: The suppression of iNOS induction by nobiletin suggests that nobiletin may be responsible for the anti-inflammatory effects of citrus peels and have a therapeutic potential for liver diseases.« less

Kinetics of the melting front movement in process of centrifugal induction surfacing of powder material with nanoscale modificaters

NASA Astrophysics Data System (ADS)

Sasnouski, I.; Kurylionak, A.

2018-03-01

For solving the problem of improving the powder coatings modified by nanostructure components obtained by induction surfacing method tribological characteristics it is necessary to study the kinetics of the powdered layer melting and define the minimum time of melting. For powdered layer predetermined temperature maintenance at sintering mode stage it is required to determine the temperature difference through blank thickness of the for one hundred-day of the define the warm-up swing on of the stocking up by solving the thermal conductivity stationary problem for quill (hollow) cylinder with internal heat source. Herewith, since in practice thickness of the cylinder wall is much less then its diameter and the temperature difference is comparatively small, the thermal conductivity dependence upon the temperature can be treated as negligible. As it was shown by our previous studies, in the induction heating process under powdered material centrifugal surfacing (i.e. before achieving the melting temperature) the temperature distribution in powdered layer thickness may be considered even. Hereinafter, considering the blank part induction heating process quasi-stationarity under Fo big values, it is possible to consider its internal surface heating as developing with constant velocity. As a result of development the melting front movement mathematical model in a powdered material with nanostructure modifiers the minimum surfacing time is defined. It allows to minimize negative impact of thermal influence on formation of applied coating structure, to raise productivity of the process, to lower power inputs and to ensure saving of nonferrous and high alloys by reducing the allowance for machining. The difference of developed mathematical model of melting front movement from previously known is that the surface temperature from which the heat transfer occures is a variable and varies with a time after the linear law.

Sensitization of interferon-γ induced apoptosis in human osteosarcoma cells by extracellular S100A4

PubMed Central

Pedersen, Kjetil Boye; Andersen, Kristin; Fodstad, Øystein; Mælandsmo, Gunhild Mari

2004-01-01

Background S100A4 is a small Ca2+-binding protein of the S100 family with metastasis-promoting properties. Recently, secreted S100A4 protein has been shown to possess a number of functions, including induction of angiogenesis, stimulation of cell motility and neurite extension. Methods Cell cultures from two human osteosarcoma cell lines, OHS and its anti-S100A4 ribozyme transfected counterpart II-11b, was treated with IFN-γ and recombinant S100A4 in order to study the sensitizing effects of extracellular S100A4 on IFN-γ mediated apoptosis. Induction of apoptosis was demonstrated by DNA fragmentation, cleavage of poly (ADP-ribose) polymerase and Lamin B. Results In the present work, we found that the S100A4-expressing human osteosarcoma cell line OHS was more sensitive to IFN-γ-mediated apoptosis than the II-11b cells. S100A4 protein was detected in conditioned medium from OHS cells, but not from II-11b cells, and addition of recombinant S100A4 to the cell medium sensitized II-11b cells to apoptosis induced by IFN-γ. The S100A4/IFN-γ-mediated induction of apoptosis was shown to be independent of caspase activation, but dependent on the formation of reactive oxygen species. Furthermore, addition of extracellular S100A4 was demonstrated to activate nuclear factor-κB (NF-κB). Conclusion In conclusion, we have shown that S100A4 sensitizes osteosarcoma cells to IFN-γ-mediated induction of apoptosis. Additionally, extracellular S100A4 activates NF-κB, but whether these events are causally related remains unknown. PMID:15318945

Parturition Events and Risk of Urinary Incontinence in Later Life

PubMed Central

Thom, David H.; Brown, Jeanette S.; Schembri, Michael; Ragins, Arona I.; Creasman, Jennifer M.; Van Den Eeden, Stephen K.

2011-01-01

Aims To examine the association between specific events during vaginal deliveries and urinary incontinence later in life. Methods A retrospective cohort study of 1521 middle-aged and older women with at least 1 vaginal delivery who were long-term members of an integrated health delivery system. Age, race/ethnicity, current incontinence status, medical, surgical history, pregnancy and parturition history, menopausal status, hormone replacement, health habits, and general health were obtained by questionnaire. Labor and delivery records, archived since 1948, were abstracted by professional medical record abstractors to obtain parturition events including induction, length of labor stages, type of anesthesia, episiotomy, instrumental delivery, and birth weight. The primary dependent variable was current weekly urinary incontinence (once per week or more often) vs urinary incontinence less than monthly (including no incontinence) in past 12 months. Associations of parturition events and later incontinence were assessed in multivariate analysis with logistic regression. Results The mean age of participants was 56 years. After adjustment for multiple risk factors, weekly urinary incontinence significantly associated with age at first birth (p=.036), greatest birth weight (p=.005), and ever having been induced for labor (OR=1.51; 95% CI=1.06–2.16, p=.02). Risk of incontinence increased from OR=1.35 (95% CI=0.92–1.97, p=0.12) for women with one induction to OR=2.67 (95% CI= 1.25–5.71, p=.01) for women with 2 or more inductions (p=0.01 for trend). No other parturition factors were associated with incontinence. Conclusions Younger age at first birth, greatest birth weight, and induction of labor were associated with an increased risk of incontinence in later life. PMID:21780171

Vertical spatial sensitivity and exploration depth of low-induction-number electromagnetic-induction instruments

USGS Publications Warehouse

Callegary, J.B.; Ferré, T.P.A.; Groom, R.W.

2007-01-01

Vertical spatial sensitivity and effective depth of exploration (d e) of low-induction-number (LIN) instruments over a layered soil were evaluated using a complete numerical solution to Maxwell's equations. Previous studies using approximate mathematical solutions predicted a vertical spatial sensitivity for instruments operating under LIN conditions that, for a given transmitter-receiver coil separation (s), coil orientation, and transmitter frequency, should depend solely on depth below the land surface. When not operating under LIN conditions, vertical spatial sensitivity and de also depend on apparent soil electrical conductivity (??a) and therefore the induction number (??). In this new evaluation, we determined the range of ??a and ?? values for which the LIN conditions hold and how de changes when they do not. Two-layer soil models were simulated with both horizontal (HCP) and vertical (VCP) coplanar coil orientations. Soil layers were given electrical conductivity values ranging from 0.1 to 200 mS m-1. As expected, de decreased as ??a increased. Only the least electrically conductive soil produced the de expected when operating under LIN conditions. For the VCP orientation, this was 1.6s, decreasing to 0.8s in the most electrically conductive soil. For the HCP orientation, de decreased from 0.76s to 0.51s. Differences between this and previous studies are attributed to inadequate representation of skin-depth effect and scattering at interfaces between layers. When using LIN instruments to identify depth to water tables, interfaces between soil layers, and variations in salt or moisture content, it is important to consider the dependence of de on ??a. ?? Soil Science Society of America.

Caco-2 cells - expression, regulation and function of drug transporters compared with human jejunal tissue.

PubMed

Brück, S; Strohmeier, J; Busch, D; Drozdzik, M; Oswald, S

2017-03-01

Induction or inhibition of drug transporting proteins by concomitantly administered drugs can cause serious drug-drug interactions (DDIs). However, in vitro assays currently available are mostly for studying the inhibitory potential of drugs on intestinal transporter proteins, rather than induction. Therefore, this study investigated the suitability of the frequently used intestinal Caco-2 cell line to predict transporter-mediated DDIs as caused by induction via activation of nuclear receptors. TaqMan® low density arrays and LC-MS/MS based targeted proteomics were used to evaluate transporter expression in Caco-2 cells in comparison with jejunal tissue, in culture-time dependence studies and after incubation with different known inducers of drug metabolism and transport. Additionally, studies on ABCB1 function were performed using Transwell® assays with [ 3 H]-digoxin and [ 3 H]-talinolol as substrates after incubation with the prototypical inducers rifampicin, St John's wort, carbamazepine and efavirenz. The gene and protein expression pattern of drug transporters in Caco-2 cells and jejunal tissue differed considerably. For some transporters culture-time dependent differences in mRNA expression and/or protein abundance could be determined. Finally, none of the studied prototypical inducers showed an effect either on mRNA expression and protein abundance or on the function of ABCB1. Differences in transporter expression in Caco-2 cells compared with jejunal tissue, as well as expression dependence on culture time must be considered in in vitro studies to avoid under- or overestimation of certain transporters. The Caco-2 cell model is not suitable for the evaluation of DDIs caused by transporter induction. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Hypoxia-inducible factor-1 (HIF-1) promotes its degradation by induction of HIF-α-prolyl-4-hydroxylases

PubMed Central

2004-01-01

An important regulator involved in oxygen-dependent gene expression is the transcription factor HIF (hypoxia-inducible factor), which is composed of an oxygen-sensitive α-subunit (HIF-1α or HIF-2α) and a constitutively expressed β-subunit. In normoxia, HIF-1α is destabilized by post-translational hydroxylation of Pro-564 and Pro-402 by a family of oxygen-sensitive dioxygenases. The three HIF-modifying human enzymes have been termed prolyl hydroxylase domain containing proteins (PHD1, PHD2 and PHD3). Prolyl hydroxylation leads to pVHL (von-Hippel-Lindau protein)-dependent ubiquitination and rapid proteasomal degradation of HIF-1α. In the present study, we report that human PHD2 and PHD3 are induced by hypoxia in primary and transformed cell lines. In the human osteosarcoma cell line, U2OS, selective suppression of HIF-1α expression by RNA interference resulted in a complete loss of hypoxic induction of PHD2 and PHD3. Induction of PHD2 by hypoxia was lost in pVHL-deficient RCC4 cells. These results suggest that hypoxic induction of PHD2 and PHD3 is critically dependent on HIF-α. Using a VHL capture assay, we demonstrate that HIF-α prolyl-4-hydroxylase capacity of cytoplasmic and nuclear protein extracts was enhanced by prolonged exposure to hypoxia. Degradation of HIF-1α after reoxygenation was accelerated, which demonstrates functional relevance of the present results. We propose a direct, negative regulatory mechanism, which limits accumulation of HIF-1α in hypoxia and leads to accelerated degradation on reoxygenation after long-term hypoxia. PMID:15104534

Plasma membrane Toll-like receptor activation increases bacterial uptake but abrogates endosomal Lactobacillus acidophilus induction of interferon-β.

PubMed

Boye, Louise; Welsby, Iain; Lund, Lisbeth Drozd; Goriely, Stanislas; Frøkiaer, Hanne

2016-11-01

Lactobacillus acidophilus induces a potent interferon-β (IFN-β) response in dendritic cells (DCs) by a Toll-like receptor 2 (TLR2) -dependent mechanism, in turn leading to strong interleukin-12 (IL-12) production. In the present study, we investigated the involvement of different types of endocytosis in the L. acidophilus-induced IFN-β and IL-12 responses and how TLR2 or TLR4 ligation by lipopolysaccharide and Pam3/4CSK4 influenced endocytosis of L. acidophilus and the induced IFN-β and IL-12 production. Lactobacillus acidophilus was endocytosed by constitutive macropinocytosis taking place in the immature cells as well as by spleen tyrosine kinase (Syk) -dependent phagocytosis but without involvement of plasma membrane TLR2. Stimulation with TLR2 or TLR4 ligands increased macropinocytosis in a Syk-independent manner. As a consequence, incubation of DCs with TLR ligands before incubation with L. acidophilus enhanced the uptake of the bacteria. However, in these experimental conditions, induction of IFN-β and IL-12 was strongly inhibited. As L. acidophilus-induced IFN-β depends on endocytosis and endosomal degradation before signalling and as TLR stimulation from the plasma membrane leading to increased macropinocytosis abrogates IFN-β induction we conclude that plasma membrane TLR stimulation leading to increased macropinocytosis decreases endosomal induction of IFN-β and speculate that this is due to competition between compartments for molecules involved in the signal pathways. In summary, endosomal signalling by L. acidophilus that leads to IFN-β and IL-12 production is inhibited by TLR stimulation from the plasma membrane. © 2016 John Wiley & Sons Ltd.

Glycans coated silver nanoparticles induces autophagy and necrosis in HeLa cells

NASA Astrophysics Data System (ADS)

Panzarini, Elisa; Mariano, Stefania; Dini, Luciana

2015-06-01

This study reports the induction of autophagy by two concentrations (2×103 or 2×104 NPs/cell) of 30 nm sized β-D-Glucose- and β-D-Glucose/Sucrose-coated silver NanoParticles (AgNPs-G and AgNPs-GS respectively) in HeLa cells treated for 6, 12, 24 and 48 hrs. Cell viability was assessed by Neutral Red (NR) test and morphological evaluation. In addition ROS generation (NBT test) and induction of apoptosis/necrosis (Annexin V/Propidium Iodide-Annexin V/PI staining) and autophagy (Monodansylcadaverine-MDC staining) were evaluated. Cytotoxicity, ROS generation and morphology changes depend on NPs type and amount, and incubation time. As a general result, AgNPs-G are more toxic than AgNPs-GS. Moreover, the lowest AgNPs-GS concentration is ineffective on cell viability and ROS generation. Only 10% and 25% of viable HeLa cells were found at the end of incubation time in the presence of higher amount of AgNPs - G and AgNPs-GS respectively and in parallel ROS generation is induced. To elucidate the type of cell death, Annexin V/PI and MDC staining was performed. Interestingly, irrespective of coating type and NPs amount the percentage of apoptotic cells (Annexin V+/PI-) is similar to viable HeLa cells. At contrary, we observed a NPs amount dependent autophagy and necrosis induction. In fact, the lower amount of NPs induces autophagy (MDC+/PI- cells) whereas the higher one induces necrosis (Annexin V+/PI+ cells). Our findings suggest that AgNPs-induced cytotoxicity depends on AgNPs amount and type and provide preliminary evidence of induction of autophagy in HeLa cells cultured in the presence of AgNPs.

Estimation of the radiation-induced DNA double-strand breaks number by considering cell cycle and absorbed dose per cell nucleus

PubMed Central

Mori, Ryosuke; Matsuya, Yusuke; Yoshii, Yuji; Date, Hiroyuki

2018-01-01

Abstract DNA double-strand breaks (DSBs) are thought to be the main cause of cell death after irradiation. In this study, we estimated the probability distribution of the number of DSBs per cell nucleus by considering the DNA amount in a cell nucleus (which depends on the cell cycle) and the statistical variation in the energy imparted to the cell nucleus by X-ray irradiation. The probability estimation of DSB induction was made following these procedures: (i) making use of the Chinese Hamster Ovary (CHO)-K1 cell line as the target example, the amounts of DNA per nucleus in the logarithmic and the plateau phases of the growth curve were measured by flow cytometry with propidium iodide (PI) dyeing; (ii) the probability distribution of the DSB number per cell nucleus for each phase after irradiation with 1.0 Gy of 200 kVp X-rays was measured by means of γ-H2AX immunofluorescent staining; (iii) the distribution of the cell-specific energy deposition via secondary electrons produced by the incident X-rays was calculated by WLTrack (in-house Monte Carlo code); (iv) according to a mathematical model for estimating the DSB number per nucleus, we deduced the induction probability density of DSBs based on the measured DNA amount (depending on the cell cycle) and the calculated dose per nucleus. The model exhibited DSB induction probabilities in good agreement with the experimental results for the two phases, suggesting that the DNA amount (depending on the cell cycle) and the statistical variation in the local energy deposition are essential for estimating the DSB induction probability after X-ray exposure. PMID:29800455

Estimation of the radiation-induced DNA double-strand breaks number by considering cell cycle and absorbed dose per cell nucleus.

PubMed

Mori, Ryosuke; Matsuya, Yusuke; Yoshii, Yuji; Date, Hiroyuki

2018-05-01

DNA double-strand breaks (DSBs) are thought to be the main cause of cell death after irradiation. In this study, we estimated the probability distribution of the number of DSBs per cell nucleus by considering the DNA amount in a cell nucleus (which depends on the cell cycle) and the statistical variation in the energy imparted to the cell nucleus by X-ray irradiation. The probability estimation of DSB induction was made following these procedures: (i) making use of the Chinese Hamster Ovary (CHO)-K1 cell line as the target example, the amounts of DNA per nucleus in the logarithmic and the plateau phases of the growth curve were measured by flow cytometry with propidium iodide (PI) dyeing; (ii) the probability distribution of the DSB number per cell nucleus for each phase after irradiation with 1.0 Gy of 200 kVp X-rays was measured by means of γ-H2AX immunofluorescent staining; (iii) the distribution of the cell-specific energy deposition via secondary electrons produced by the incident X-rays was calculated by WLTrack (in-house Monte Carlo code); (iv) according to a mathematical model for estimating the DSB number per nucleus, we deduced the induction probability density of DSBs based on the measured DNA amount (depending on the cell cycle) and the calculated dose per nucleus. The model exhibited DSB induction probabilities in good agreement with the experimental results for the two phases, suggesting that the DNA amount (depending on the cell cycle) and the statistical variation in the local energy deposition are essential for estimating the DSB induction probability after X-ray exposure.

Control of B-cell responses by Toll-like receptors

NASA Astrophysics Data System (ADS)

Pasare, Chandrashekhar; Medzhitov, Ruslan

2005-11-01

Toll-like receptors (TLRs) detect microbial infection and have an essential role in the induction of immune responses. TLRs can directly induce innate host defence responses, but the mechanisms of TLR-mediated control of adaptive immunity are not fully understood. Although TLR-induced dendritic cell maturation is required for activation of T-helper (TH) cells, the role of TLRs in B-cell activation and antibody production in vivo is not yet known. Here we show that activation and differentiation of TH cells is not sufficient for the induction of T-dependent B-cell responses. We find that, in addition to CD4+ T-cell help, generation of T-dependent antigen-specific antibody responses requires activation of TLRs in B cells.

Measurement of the target current by inductive probe during laser interaction on terawatt laser system PALS.

PubMed

Cikhardt, J; Krása, J; De Marco, M; Pfeifer, M; Velyhan, A; Krouský, E; Cikhardtová, B; Klír, D; Rezáč, K; Ullschmied, J; Skála, J; Kubeš, P; Kravárik, J

2014-10-01

Measurements of the return-current flowing through a solid target irradiated with the sub-nanosecond kJ-class Prague Asterix Laser System is reported. A new inductive target probe was developed which allows us measuring the target current derivative in a kA/ns range. The dependences of the target current on the laser pulse energy for cooper, graphite, and polyethylene targets are reported. The experiment shows that the target current is proportional to the deposited laser energy and is strongly affected by the shot-to-shot fluctuations. The corresponding maximum target charge exceeded a value of 10 μC. A return-current dependence of the electromagnetic pulse produced by the laser-target interaction is presented.

Ultra-low field nuclear magnetic resonance and magnetic resonance imaging to discriminate and identify materials

DOEpatents

Matlashov, Andrei Nikolaevich; Urbaitis, Algis V.; Savukov, Igor Mykhaylovich; Espy, Michelle A.; Volegov, Petr Lvovich; Kraus, Jr., Robert Henry

2013-03-05

Method comprising obtaining an NMR measurement from a sample wherein an ultra-low field NMR system probes the sample and produces the NMR measurement and wherein a sampling temperature, prepolarizing field, and measurement field are known; detecting the NMR measurement by means of inductive coils; analyzing the NMR measurement to obtain at least one measurement feature wherein the measurement feature comprises T1, T2, T1.rho., or the frequency dependence thereof; and, searching for the at least one measurement feature within a database comprising NMR reference data for at least one material to determine if the sample comprises a material of interest.

Modified Bloch equations and spectral hole burning in solids

NASA Astrophysics Data System (ADS)

Asadullina, N. Ya; Asadullin, T. Ya; Asadullin, Ya Ya

2001-06-01

On the grounds of Bloch equations modified by taking into account the power dependence of the dispersion and damping parameters, we give general expressions for hole shapes burnt in the absorption and polarization spectra of the two-level systems. The general expressions are used for detailed numerical calculations of the hole shapes and hole widths in a concrete paramagnetic system (quartz with [AlO4]0 centres). This system earlier was studied experimentally and theoretically through the transient nutation and free induction decay methods. The results on the hole width in our modified-Bloch-equations model are in good qualitative agreement with the FID data.

Hypoxia triggers a proangiogenic pathway involving cancer cell microvesicles and PAR-2–mediated heparin-binding EGF signaling in endothelial cells

PubMed Central

Svensson, Katrin J.; Kucharzewska, Paulina; Christianson, Helena C.; Sköld, Stefan; Löfstedt, Tobias; Johansson, Maria C.; Mörgelin, Matthias; Bengzon, Johan; Ruf, Wolfram; Belting, Mattias

2011-01-01

Highly malignant tumors, such as glioblastomas, are characterized by hypoxia, endothelial cell (EC) hyperplasia, and hypercoagulation. However, how these phenomena of the tumor microenvironment may be linked at the molecular level during tumor development remains ill-defined. Here, we provide evidence that hypoxia up-regulates protease-activated receptor 2 (PAR-2), i.e., a G-protein–coupled receptor of coagulation-dependent signaling, in ECs. Hypoxic induction of PAR-2 was found to elicit an angiogenic EC phenotype and to specifically up-regulate heparin-binding EGF-like growth factor (HB-EGF). Inhibition of HB-EGF by antibody neutralization or heparin treatment efficiently counteracted PAR-2–mediated activation of hypoxic ECs. We show that PAR-2–dependent HB-EGF induction was associated with increased phosphorylation of ERK1/2, and inhibition of ERK1/2 phosphorylation attenuated PAR-2–dependent HB-EGF induction as well as EC activation. Tissue factor (TF), i.e., the major initiator of coagulation-dependent PAR signaling, was substantially induced by hypoxia in several types of cancer cells, including glioblastoma; however, TF was undetectable in ECs even at prolonged hypoxia, which precludes cell-autonomous PAR-2 activation through TF. Interestingly, hypoxic cancer cells were shown to release substantial amounts of TF that was mainly associated with secreted microvesicles with exosome-like characteristics. Vesicles derived from glioblastoma cells were found to trigger TF/VIIa–dependent activation of hypoxic ECs in a paracrine manner. We provide evidence of a hypoxia-induced signaling axis that links coagulation activation in cancer cells to PAR-2–mediated activation of ECs. The identified pathway may constitute an interesting target for the development of additional strategies to treat aggressive brain tumors. PMID:21788507

Hypoxia triggers a proangiogenic pathway involving cancer cell microvesicles and PAR-2-mediated heparin-binding EGF signaling in endothelial cells.

PubMed

Svensson, Katrin J; Kucharzewska, Paulina; Christianson, Helena C; Sköld, Stefan; Löfstedt, Tobias; Johansson, Maria C; Mörgelin, Matthias; Bengzon, Johan; Ruf, Wolfram; Belting, Mattias

2011-08-09

Highly malignant tumors, such as glioblastomas, are characterized by hypoxia, endothelial cell (EC) hyperplasia, and hypercoagulation. However, how these phenomena of the tumor microenvironment may be linked at the molecular level during tumor development remains ill-defined. Here, we provide evidence that hypoxia up-regulates protease-activated receptor 2 (PAR-2), i.e., a G-protein-coupled receptor of coagulation-dependent signaling, in ECs. Hypoxic induction of PAR-2 was found to elicit an angiogenic EC phenotype and to specifically up-regulate heparin-binding EGF-like growth factor (HB-EGF). Inhibition of HB-EGF by antibody neutralization or heparin treatment efficiently counteracted PAR-2-mediated activation of hypoxic ECs. We show that PAR-2-dependent HB-EGF induction was associated with increased phosphorylation of ERK1/2, and inhibition of ERK1/2 phosphorylation attenuated PAR-2-dependent HB-EGF induction as well as EC activation. Tissue factor (TF), i.e., the major initiator of coagulation-dependent PAR signaling, was substantially induced by hypoxia in several types of cancer cells, including glioblastoma; however, TF was undetectable in ECs even at prolonged hypoxia, which precludes cell-autonomous PAR-2 activation through TF. Interestingly, hypoxic cancer cells were shown to release substantial amounts of TF that was mainly associated with secreted microvesicles with exosome-like characteristics. Vesicles derived from glioblastoma cells were found to trigger TF/VIIa-dependent activation of hypoxic ECs in a paracrine manner. We provide evidence of a hypoxia-induced signaling axis that links coagulation activation in cancer cells to PAR-2-mediated activation of ECs. The identified pathway may constitute an interesting target for the development of additional strategies to treat aggressive brain tumors.

Taxifolin synergizes Andrographolide-induced cell death by attenuation of autophagy and augmentation of caspase dependent and independent cell death in HeLa cells

PubMed Central

Alzaharna, Mazen; Alqouqa, Iyad; Cheung, Hon-Yeung

2017-01-01

Andrographolide (Andro) has emerged recently as a potential and effective anticancer agent with induction of apoptosis in some cancer cell lines while induction of G2/M arrest with weak apoptosis in others. Few studies have proved that Andro is also effective in combination therapy. The flavonoid Taxifolin (Taxi) has showed anti-oxidant and antiproliferative effects against different cancer cells. Therefore, the present study investigated the cytotoxic effects of Andro alone or in combination with Taxi on HeLa cells. The combination of Andro with Taxi was synergistic at all tested concentrations and combination ratios. Andro alone induced caspase-dependent apoptosis which was enhanced by the combination with Taxi and attenuated partly by using Z-Vad-Fmk. Andro induced a protective reactive oxygen species (ROS)-dependent autophagy which was attenuated by Taxi. The activation of p53 was involved in Andro-induced autophagy where the use of Taxi or pifithrin-α (PFT-α) decreased it while the activation of JNK was involved in the cell death of HeLa cells but not in the induction of autophagy. The mitochondrial outer-membrane permeabilization (MOMP) plays an important role in Andro-induced cell death in HeLa cells. Andro alone increased the MOMP which was further increased in the case of combination. This led to the increase in AIF and cytochrome c release from mitochondria which consequently increased caspase-dependent and independent cell death. In conclusion, Andro induced a protective autophagy in HeLa cells which was reduced by Taxi and the cell death was increased by increasing the MOMP and subsequently the caspase-dependent and independent cell death. PMID:28182713

Combinatorial programming of human neuronal progenitors using magnetically-guided stoichiometric mRNA delivery.

PubMed

Azimi, Sayyed M; Sheridan, Steven D; Ghannad-Rezaie, Mostafa; Eimon, Peter M; Yanik, Mehmet Fatih

2018-05-01

Identification of optimal transcription-factor expression patterns to direct cellular differentiation along a desired pathway presents significant challenges. We demonstrate massively combinatorial screening of temporally-varying mRNA transcription factors to direct differentiation of neural progenitor cells using a dynamically-reconfigurable magnetically-guided spotting technology for localizing mRNA, enabling experiments on millimetre size spots. In addition, we present a time-interleaved delivery method that dramatically reduces fluctuations in the delivered transcription-factor copy-numbers per cell. We screened combinatorial and temporal delivery of a pool of midbrain-specific transcription factors to augment the generation of dopaminergic neurons. We show that the combinatorial delivery of LMX1A, FOXA2 and PITX3 is highly effective in generating dopaminergic neurons from midbrain progenitors. We show that LMX1A significantly increases TH -expression levels when delivered to neural progenitor cells either during proliferation or after induction of neural differentiation, while FOXA2 and PITX3 increase expression only when delivered prior to induction, demonstrating temporal dependence of factor addition. © 2018, Azimi et al.

Effects of Casting Conditions on the Structure and Magnetic Properties of the Co-19 at.%Al-6 at. %W Alloy

NASA Astrophysics Data System (ADS)

Kazantseva, N. V.; Stepanova, N. N.; Rigmant, M. B.; Davidov, D. I.; Shishkin, D. A.; Romanov, E. P.

The Co-19 at.%Al-6 at.%W alloy was prepared by two methods of casting. We used arc melting under an argon atmosphere with casting into a copper water-cooled casting mold and induction melting furnace with casting into a ceramic Al2O3 mold. According to the X-ray and SEM analyses, phase compositions depend on the cooling rate of the ingot after melting. After arc melting, the cast alloy has a three-phase structure, consisting of γ cobalt (FCC), intermetallic phases CoAl (B2) type, and Co3W (DO19) type. After the induction melting, the alloy has a three-phase structure, consisting of γ cobalt (FCC), intermetallic phases CoAl (B2) type, and Co7W6 (µ) type. All phases in the investigated ternary alloy at the room temperature are ferromagnetic. Curie temperatures of all obtained phases were defined. It is shown that the magnetic properties of the studied alloy are typical for soft magnetic materials.

Ultra-Sensitive Elemental Analysis Using Plasmas 4.Application of Inductively Coupled Plasma Mass Spectrometry to the Study of Environmental Radioactivity

NASA Astrophysics Data System (ADS)

Yoshida, Satoshi

Applications of inductively coupled plasma mass spectrometry (ICP-MS) to the determination of long-lived radionuclides in environmental samples were summarized. In order to predict the long-term behavior of the radionuclides, related stable elements were also determined. Compared with radioactivity measurements, the ICP-MS method has advantages in terms of its simple analytical procedures, prompt measurement time, and capability of determining the isotope ratio such as240Pu/239Pu, which can not be separated by radiation. Concentration of U and Th in Japanese surface soils were determined in order to determine the background level of the natural radionuclides. The 235U/238U ratio was successfully used to detect the release of enriched U from reconversion facilities to the environment and to understand the source term. The 240Pu/239Pu ratios in environmental samples varied widely depending on the Pu sources. Applications of ICP-MS to the measurement of I and Tc isotopes were also described. The ratio between radiocesium and stable Cs is useful for judging the equilibrium of deposited radiocesium in a forest ecosystem.

Induction of CYP3A4 by efavirenz in primary human hepatocytes: comparison with rifampin and phenobarbital.

PubMed

Hariparsad, Niresh; Nallani, Srikanth C; Sane, Rucha S; Buckley, Donna J; Buckley, Arthur R; Desai, Pankaj B

2004-11-01

The antiretroviral agent efavirenz enhances the systemic clearance of coadministered drugs that are cytochrome P450 (CYP) 3A4 substrates. The mechanism of the apparent increase in CYP3A4 activity by efavirenz and the magnitude of change relative to other known inducers are not known. The authors tested the hypothesis that increased enzymatic activity by efavirenz entails CYP3A4 induction and activation of the human pregnane X receptor (hPXR), a key transcriptional regulator of CYP3A4. Employing primary cultures of human hepatocytes, they compared the CYP3A4 inductive effects of efavirenz (1-10 microM) to rifampin (10 microM) and phenobarbital (2 mM). A cell-based reporter assay was employed to assess hPXR activation. The authors observed that efavirenz caused a concentration-dependent CYP3A4 induction and hPXR activation. Based on the CYP3A4 activity assay, the average magnitude of induction by efavirenz (5-10 microM) was approximately 3- to 4-fold. In comparison, phenobarbital (2 mM) and rifampin (10 microM) caused a 5- and 6-fold induction, respectively.

Tissue Plasminogen Activator Induction in Purkinje Neurons After Cerebellar Motor Learning

NASA Astrophysics Data System (ADS)

Seeds, Nicholas W.; Williams, Brian L.; Bickford, Paula C.

1995-12-01

The cerebellar cortex is implicated in the learning of complex motor skills. This learning may require synaptic remodeling of Purkinje cell inputs. An extracellular serine protease, tissue plasminogen activator (tPA), is involved in remodeling various nonneural tissues and is associated with developing and regenerating neurons. In situ hybridization showed that expression of tPA messenger RNA was increased in the Purkinje neurons of rats within an hour of their being trained for a complex motor task. Antibody to tPA also showed the induction of tPA protein associated with cerebellar Purkinje cells. Thus, the induction of tPA during motor learning may play a role in activity-dependent synaptic plasticity.

High density growth of T7 expression strains with auto-induction option

DOEpatents

Studier, F. William

2010-07-20

A bacterial growth medium for promoting auto-induction of transcription of cloned DNA in cultures of bacterial cells grown batchwise is disclosed. The transcription is under the control of a lac repressor. Also disclosed is a bacterial growth medium for improving the production of a selenomethionine-containing protein or polypeptide in a bacterial cell, the protein or polypeptide being produced by recombinant DNA techniques from a lac or T7lac promoter, the bacterial cell encoding a vitamin B12-dependent homocysteine methylase. Finally, disclosed is a bacterial growth medium for suppressing auto-induction of expression in cultures of bacterial cells grown batchwise, said transcription being under the control of lac repressor.

The Exploration of Role Induction as a Potential Method for Improving Men's Perceptions of Career Counseling

ERIC Educational Resources Information Center

Kantamneni, Neeta; Christianson, Heidi Fowell; Smothers, Melissa Kraemer; Wester, Stephen R.

2011-01-01

The authors explored the influence of role induction on men's perceptions of career counseling and attitudes toward seeking professional help. Two separate role inductions were presented to 268 male college students; the first discussed holistic career counseling, and the second integrated a discussion of male gender role socialization. Results…

40 CFR Appendix A to Subpart C of... - Alternative Testing Methods Approved for Analyses Under the Safe Drinking Water Act

Code of Federal Regulations, 2010 CFR

2010-07-01

... Absorption D 3697-07 Atomic Absorption; Furnace 3113 B Axially viewed inductively coupled plasma-atomic... C Hydride Atomic Absorption 3114 B D 2972-08 B Axially viewed inductively coupled plasma-atomic emission spectrometry (AVICP-AES) 200.5, Revision 4.2. Barium Inductively Coupled Plasma 3120 B Atomic...

High magnetic field ohmically decoupled non-contact technology

DOEpatents

Wilgen, John [Oak Ridge, TN; Kisner, Roger [Knoxville, TN; Ludtka, Gerard [Oak Ridge, TN; Ludtka, Gail [Oak Ridge, TN; Jaramillo, Roger [Knoxville, TN

2009-05-19

Methods and apparatus are described for high magnetic field ohmically decoupled non-contact treatment of conductive materials in a high magnetic field. A method includes applying a high magnetic field to at least a portion of a conductive material; and applying an inductive magnetic field to at least a fraction of the conductive material to induce a surface current within the fraction of the conductive material, the surface current generating a substantially bi-directional force that defines a vibration. The high magnetic field and the inductive magnetic field are substantially confocal, the fraction of the conductive material is located within the portion of the conductive material and ohmic heating from the surface current is ohmically decoupled from the vibration. An apparatus includes a high magnetic field coil defining an applied high magnetic field; an inductive magnetic field coil coupled to the high magnetic field coil, the inductive magnetic field coil defining an applied inductive magnetic field; and a processing zone located within both the applied high magnetic field and the applied inductive magnetic field. The high magnetic field and the inductive magnetic field are substantially confocal, and ohmic heating of a conductive material located in the processing zone is ohmically decoupled from a vibration of the conductive material.

Differential DNases are selectively used in neuronal apoptosis depending on the differentiation state.

PubMed

Shiokawa, D; Tanuma, S

2004-10-01

In this study, we investigate the roles of two apoptotic endonucleases, CAD and DNase gamma, in neuronal apoptosis. High expression of CAD, but not DNase gamma, is detected in proliferating N1E-115 neuroblastoma cells, and apoptotic DNA fragmentation induced by staurosporine under proliferating conditions is abolished by the expression of a caspase-resistant form of ICAD. After the induction of neuronal differentiation, CAD disappearance and the induction of DNase gamma occur simultaneously in N1E-115 cells. Apoptotic DNA fragmentation that occurs under differentiating conditions is suppressed by the downregulation of DNase gamma caused by its antisense RNA. The induction of DNase gamma is also observed during neuronal differentiation of PC12 cells, and apoptotic DNA fragmentation induced by NGF deprivation is inhibited by the antisense-mediated downregulation of DNase gamma. These observations suggest that DNA fragmentation in neuronal apoptosis is catalyzed by either CAD or DNase gamma depending on the differentiation state. Furthermore, DNase gamma is suggested to be involved in naturally occurring apoptosis in developing nervous systems.

Transgenic HFE-dependent induction of hepcidin in mice does not require transferrin receptor-2.

PubMed

Schmidt, Paul J; Fleming, Mark D

2012-06-01

Hereditary hemochomatosis (HH) is caused by mutations in several genes, including HFE and transferrin receptor-2 (TFR2). Loss of either protein decreases expression of the iron regulatory hormone hepcidin by the liver, leading to inappropriately high iron uptake from the diet, and resulting in systemic iron overload. In tissue culture, overexpressed HFE and TFR2 physically interact. Hepatocellular overexpression of Hfe in vivo increases hepcidin expression, despite an associated decrease in Tfr2. On this basis, we hypothesized that Tfr2 would not be required for Hfe-dependent up-regulation of hepcidin. We show that hepatocellular overexpression of Hfe in Tfr2(Y245X/Y245X) mice leads to hepcidin induction eventuating in iron deficiency and a hypochromic, microcytic anemia. Furthermore, coimmunoprecipitation studies using liver lysates did not provide evidence for physical interaction between Hfe and Tfr2 in vivo. In conclusion, we demonstrate that Tfr2 is not essential for Hfe-mediated induction of hepcidin expression, supporting the possibility that TFR2 may regulate iron metabolism in an HFE-independent manner. Copyright © 2012 Wiley Periodicals, Inc.

Transgenic HFE-dependent induction of hepcidin in mice does not require transferrin receptor-2

PubMed Central

Schmidt, Paul J.; Fleming, Mark D.

2012-01-01

Hereditary hemochomatosis (HH) is caused by mutations in several genes, including HFE and transferrin receptor-2 (TFR2). Loss of either protein decreases expression of the iron regulatory hormone hepcidin by the liver, leading to inappropriately high iron uptake from the diet, and resulting in systemic iron overload. In tissue culture, overexpressed HFE and TFR2 physically interact. Hepatocellular overexpression of Hfe in vivo increases hepcidin expression, despite an associated decrease in Tfr2. On this basis, we hypothesized that Tfr2 would not be required for Hfe-dependent up-regulation of hepcidin. We show that hepatocellular overexpression of Hfe in Tfr2Y245X/Y245X mice leads to hepcidin induction eventuating in iron deficiency and a hypochromic, microcytic anemia. Furthermore, co-immunoprecipitation studies using liver lysates did not provide evidence for physical interaction between Hfe and Tfr2 in vivo. In conclusion, we demonstrate that Tfr2 is not essential for Hfe-mediated induction of hepcidin expression, supporting the possibility that TFR2 may regulate iron metabolism in an HFE-independent manner. PMID:22460705

Hyperosmolarity leads to an increase in derepressed system A activity in the renal epithelial cell line NBL-1.

PubMed Central

Soler, C; Felipe, A; Casado, F J; McGivan, J D; Pastor-Anglada, M

1993-01-01

Hyperosmolarity induced an increase in Na(+)-dependent L-alanine uptake in confluent monolayers of the established renal epithelial cell line NBL-1. This induction was attributable to system A and was only seen when the cells had been previously deprived of amino acids in the culture medium to derepress system A activity. It was additive to the adaptive regulation induction, and both were inhibited by cycloheximide. However, the hyperosmolarity effect was inhibited by colcemid (an inhibitor of microtubular function), but adaptive regulation was not. Otherwise, when cell monolayers were incubated in a control medium, basal Na(+)-dependent L-alanine uptake mediated by system B0 decreased. The results of this study show that: (i) system A activity was not induced by cell shrinkage and subsequent swelling due to extracellular hyperosmolarity when cells were incubated in control medium; (ii) previous expression of system A activity induced by amino acid starvation seems to be a prerequisite for further induction due to hyperosmolarity; and (iii) the effects of adaptive regulation and hyperosmotic stress are mediated by different mechanisms. PMID:8435065

Quantification and Compensation of Eddy-Current-Induced Magnetic Field Gradients

PubMed Central

Spees, William M.; Buhl, Niels; Sun, Peng; Ackerman, Joseph J.H.; Neil, Jeffrey J.; Garbow, Joel R.

2011-01-01

Two robust techniques for quantification and compensation of eddy-current-induced magnetic-field gradients and static magnetic-field shifts (ΔB0) in MRI systems are described. Purpose-built 1-D or 6-point phantoms are employed. Both procedures involve measuring the effects of a prior magnetic-field-gradient test pulse on the phantom’s free induction decay (FID). Phantom-specific analysis of the resulting FID data produces estimates of the time-dependent, eddy-current-induced magnetic field gradient(s) and ΔB0 shift. Using Bayesian methods, the time dependencies of the eddy-current-induced decays are modeled as sums of exponentially decaying components, each defined by an amplitude and time constant. These amplitudes and time constants are employed to adjust the scanner’s gradient pre-emphasis unit and eliminate undesirable eddy-current effects. Measurement with the six-point sample phantom allows for simultaneous, direct estimation of both on-axis and cross-term eddy-current-induced gradients. The two methods are demonstrated and validated on several MRI systems with actively-shielded gradient coil sets. PMID:21764614

Quantification and compensation of eddy-current-induced magnetic-field gradients.

PubMed

Spees, William M; Buhl, Niels; Sun, Peng; Ackerman, Joseph J H; Neil, Jeffrey J; Garbow, Joel R

2011-09-01

Two robust techniques for quantification and compensation of eddy-current-induced magnetic-field gradients and static magnetic-field shifts (ΔB0) in MRI systems are described. Purpose-built 1-D or six-point phantoms are employed. Both procedures involve measuring the effects of a prior magnetic-field-gradient test pulse on the phantom's free induction decay (FID). Phantom-specific analysis of the resulting FID data produces estimates of the time-dependent, eddy-current-induced magnetic field gradient(s) and ΔB0 shift. Using Bayesian methods, the time dependencies of the eddy-current-induced decays are modeled as sums of exponentially decaying components, each defined by an amplitude and time constant. These amplitudes and time constants are employed to adjust the scanner's gradient pre-emphasis unit and eliminate undesirable eddy-current effects. Measurement with the six-point sample phantom allows for simultaneous, direct estimation of both on-axis and cross-term eddy-current-induced gradients. The two methods are demonstrated and validated on several MRI systems with actively-shielded gradient coil sets. Copyright © 2011 Elsevier Inc. All rights reserved.

Mineralization by mesenchymal stromal cells is variously modulated depending on commercial platelet lysate preparations.

PubMed

Boraldi, Federica; Burns, Jorge S; Bartolomeo, Angelica; Dominici, Massimo; Quaglino, Daniela

2018-03-01

Numerous cellular models have been developed to investigate calcification for regenerative medicine applications and for the identification of therapeutic targets in various complications associated with age-related diseases. However, results have often been contradictory due to specific culture conditions, cell type ontogeny and aging status. Human platelet lysate (hPL) has been recently investigated as valuable alternative to fetal bovine serum (FBS) in cell culture and bone regeneration. A parallel comparison of how all these multiple factors may converge to influence mineralization has yet to be reported. To compare mineralization of human mesenchymal cell types known to differ in extracellular matrix calcification potency, bone marrow-derived mesenchymal stromal cells and dermal fibroblasts from neonatal and adult donors, at both low and high passages, were investigated in an ex vivo experimental model by supplementing the osteogenic induction medium with FBS or with hPL. Four commercial hPL preparations were profiled by liquid chromatography/electrospray ionization quadrupole time-of-flight spectrometry, and mineralization was visualized by von Kossa staining and quantified by morphometric evaluations after 9, 14 and 21 days of culture. Data demonstrate that (i) commercial hPL preparations differ according to mass spectra profiles, (ii) hPL variously influences mineral deposition depending on cell line and possibly on platelet product preparation methods, (iii) donor age modifies mineral deposition in the presence of the same hPL and (iv) reduced in vitro proliferative capacity affects osteogenic induction and response to hPL. Despite the standardized procedures applied to obtain commercial hPL, this study highlights the divergent effects of different preparations and emphasizes the importance of cellular ontology, donor age and cell proliferative capacity to optimize the osteogenic induction capabilities of mesenchymal stromal cells and design more effective cell-based therapeutic protocols. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Induction and repair of DNA double-strand breaks in rat cerebellar cortex exposed to 60Co γ-rays

NASA Astrophysics Data System (ADS)

Bulanova, T. S.; Zadneprianetc, M. G.; Ježková, L.; Kruglyakova, E. A.; Smirnova, E. V.; Boreyko, A. V.

2018-01-01

The induction and repair of DNA double-strand breaks are studied using the immunohistochemical staining procedure of paraffin-embedded rat cerebellum tissues after exposure to γ-rays of 60Co. The dose dependence of radiation-induced colocalized γH2AX/53BP1 foci is studied and its linear character is established. It is shown that these foci are efficiently eliminated 24 h after irradiation.

Protein Kinase M[Zeta] Is Essential for the Induction and Maintenance of Dopamine-Induced Long-Term Potentiation in Apical CA1 Dendrites

ERIC Educational Resources Information Center

Navakkode, Sheeja; Sajikumar, Sreedharan; Sacktor, Todd Charlton; Frey, Julietta U.

2010-01-01

Dopaminergic D1/D5-receptor-mediated processes are important for certain forms of memory as well as for a cellular model of memory, hippocampal long-term potentiation (LTP) in the CA1 region of the hippocampus. D1/D5-receptor function is required for the induction of the protein synthesis-dependent maintenance of CA1-LTP (L-LTP) through activation…

Giant magneto-impedance and magneto-inductive effects in amorphous alloys

NASA Astrophysics Data System (ADS)

Panina, L. V.; Mohri, K.; Bushida, K.; Noda, M.

1994-11-01

Recent experiments have discovered giant and sensitive magneto-impedance and magneto-inductive effects in FeCoSiB amorphous wires. These effects include a sensitive change in an ac wire voltage with the application of a small dc longitudinal magnetic field. At low frequencies (1-10 kHz) the inductive voltage drops by 50% for a field of 2 Oe (25%/Oe) reflecting a strong field dependence of the circumferential permeability. At higher frequencies (0.1-10 MHz) when the skin effect is essential, the amplitude of the total wire voltage decreases by 40%-60% for fields of 3-10 Oe (about 10%/Oe). These effects exhibit no hysteresis for the variation of an applied field and can be obtained even in wires of 1 mm length and a few micrometer diameter. These characteristics are very useful to constitute a highly sensitive microsensor head to detect local fields of the order of 10(exp -5) Oe. In this paper, we review recently obtained experimental results on magneto-inductive and magneto-impedance effects and present a detailed discussion for their mechanism, developing a general approach in terms of ac complex impedance in a magnetic conductor. In the case of a strong skin effect the total wire impedance depends on the circumferential permeability through the penetration depth, resulting in the giant magneto-impedance effect.

Role of tumor necrosis factor-α and interleukin-1β in anorexia induction following oral exposure to the trichothecene deoxynivalenol (vomitoxin) in the mouse.

PubMed

Wu, Wenda; Zhang, Haibin

2014-01-01

The trichothecene deoxynivalenol (DON), a foodborne mycotoxin found in grain-based foods, has been associated with human and animal food poisoning. Although induction of anorexia has been described as a hallmark of DON-induced toxicity in many animal species, the mechanistic basis for this adverse effect is not fully understood. The purpose of this research was to determine the role of two proinflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in DON-induced anorexia. In a nocturnal mouse food consumption model, DON-induced anorectic response occurred at 1 hr and lasted up to 6 hr. Similar anorectic effects were observed following acute administration of exogenous TNF-α and IL-1β. Oral exposure to DON at 5 mg/kg bw stimulated splenic and hepatic mRNA and plasma protein elevations of TNF-α and IL-1β that corresponded to anorexia induction. Pretreatment with the TNF-α receptor (TNFR) antagonist R-7050 dose-dependently attenuated both TNF-α- and DON-induced anorexia. While, the type 1 IL-1 receptor (IL-1R1) antagonist IL-1RA dose-dependently attenuated both IL-1β- and DON-induced anorexia. Taken together, the results suggest that both TNF-α and IL-1β play contributory role in anorexia induction following oral exposure to DON.

15-Deoxy-{delta}{sup 12,14}-prostaglandin J{sub 2}-induced down-regulation of endothelial nitric oxide synthase in association with HSP70 induction

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

Hwang, Jinah; Lee, Hyun-Il; Chang, Young-Sun

2007-05-25

A natural ligand of peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}), 15-deoxy-{delta}{sup 12,14}-prostaglandin J{sub 2} (15d-PGJ{sub 2}), decreases endothelial nitric oxide synthase (eNOS) expression by an unknown mechanism. Here we found that 15d-PGJ{sub 2}-induced eNOS reduction is inversely associated with heat shock protein 70 (HSP70) induction in endothelial cells. Treatment of cells with 15d-PGJ{sub 2} decreased eNOS protein expression in a concentration- and time-dependent manner, but independently of PPAR{gamma} with no effect on mRNA levels. Although 15d-PGJ{sub 2} elicited endothelial apoptosis, inhibition of both pan-caspases and cathepsins failed to reverse reduction of eNOS protein. Interestingly, we observed that 15d-PGJ{sub 2} induced HSP70more » in a dose-dependent manner. Immunoprecipitation and heat shock treatment demonstrated that eNOS reduction was strongly related to HSP70 induction. Cellular fractionation revealed that treatment with 15d-PGJ{sub 2} increased eNOS distribution 2.5-fold from soluble to insoluble fractions. These findings provide new insights into mechanisms whereby eNOS regulation by 15d-PGJ{sub 2} is related to HSP70 induction.« less

Method and graphs for the evaluation of air-induction systems

NASA Technical Reports Server (NTRS)

Brajnikoff, George B

1953-01-01

Graphs have been developed for rapid evaluation of air-induction systems from considerations of their aerodynamic-performance parameters in combination with power-plant characteristics. The graphs cover the range of supersonic Mach numbers to 3.0. Examples are presented for an air-induction system and engine combination of two Mach numbers and two altitudes in order to illustrate the method and application of the graphs. The examples show that jet-engine characteristics impose restrictions on the use of fixed inlets if the maximum net thrusts are to be realized at all flight conditions. (author)

ACOG Committee Opinion no. 597: Committee on Obstetric Practice: Labor induction or augmentation and autism.

PubMed

2014-05-01

Functional oxytocin deficiency and a faulty oxytocin signaling pathway have been observed in conjunction with autism spectrum disorder (ASD). Because exogenous synthetic oxytocin commonly is administered for labor induction and augmentation, some have hypothesized that synthetic oxytocin used for these purposes may alter fetal oxytocin receptors and predispose exposed offspring to ASD. However, current evidence does not identify a causal relationship between labor induction or augmentation in general, or oxytocin labor induction specifically, and autism or ASD. Recognizing the limitations of available study design, conflicting data, and the potential consequences of limiting labor induction and augmentation, the Committee on Obstetric Practice recommends against a change in current guidance regarding counseling and indications for and methods of labor induction and augmentation.

The effect of preoperative suggestions on perioperative dreams and dream recalls after administration of different general anesthetic combinations: a randomized trial in maxillofacial surgery.

PubMed

Gyulaházi, Judit; Varga, Katalin; Iglói, Endre; Redl, Pál; Kormos, János; Fülesdi, Béla

2015-01-01

Images evoked immediately before the induction of anesthesia with the help of suggestions may influence dreaming during anesthesia.The aim of the study was to assess the incidence of evoked dreams and dream recalls by employing suggestions before induction of anesthesia while administering different general anesthetic combinations. This is a single center, prospective randomized including 270 adult patients scheduled for maxillofacial surgical interventions. Patients were assigned to control, suggestion and dreamfilm groups according to the psychological method used. According to the anesthetic protocol there were also three subgroups: etomidate & sevoflurane, propofol & sevoflurane, propofol & propofol groups. Primary outcome measure was the incidence of postoperative dreams in the non-intervention group and in the three groups receiving different psychological interventions. Secondary endpoint was to test the effect of perioperative suggestions and dreamfilm-formation training on the occurrance of dreams and recallable dreams in different general anesthesiological techniques. Dream incidence rates measured in the control group did not differ significantly (etomidate & sevoflurane: 40%, propofol & sevoflurane: 26%, propofol & propofol: 39%). A significant increase could be observed in the incidence rate of dreams between the control and suggestion groups in the propofol & sevoflurane (26%-52%) group (p = 0.023). There was a significant difference in the incidence of dreams between the control and dreamfilm subgroup in the propofol & sevoflurane (26% vs. 57%), and in the propofol & propofol group (39% vs.70%) (p = 0.010, and p = 0.009, respectively). Similar to this, there was a significant difference in dream incidence between the dreamfilm and the suggestion subgroups (44% vs. 70%) in the propofol & propofol group (p = 0.019). Propofol as an induction agent contributed most to dream formation and recalls (χ2-test p value: 0.005). The content of images and dreams evoked using suggestions showed great agreement using all three anesthetic protocols. The psychological method influenced dreaming during anesthesia. The increase of the incidence rate of dreams was dependent on the anesthetic agent used, especially the induction agent. The study was registered in ClinicalTrials.gov. Identifier: NCT01839201.

Application of high performance liquid chromatography with inductively coupled plasma mass spectrometry (HPLC-ICP-MS) for determination of chromium compounds in the air at the workplace.

PubMed

Stanislawska, Magdalena; Janasik, Beata; Wasowicz, Wojciech

2013-12-15

The toxicity and bioavailability of chromium species are highly dependable on the form or species, therefore determination of total chromium is insufficient for a complete toxicological evaluation and risk assessment. An analytical method for determination of soluble and insoluble Cr (III) and Cr (VI) compounds in welding fume at workplace air has been developed. The total chromium (Cr) was determined by using quadruple inductively coupled plasma mass spectrometry (ICP-MS) equipped with a dynamic reaction cell (DRC(®)). Soluble trivalent and hexavalent chromium compounds were determined by high performance liquid chromatography with inductively coupled plasma mass spectrometry (HPLC-ICP-MS). A high-speed, reversed-phase CR C8 column (PerkinElmer, Inc., Shelton, CT, USA) was used for the speciation of soluble Cr (III) and soluble Cr (VI). The separation was accomplished by interaction of the chromium species with the different components of the mobile phase. Cr (III) formed a complex with EDTA, i.e. retained on the column, while Cr (VI) existed in the solutions as dichromate. Alkaline extraction (2% KOH and 3% Na2CO3) and anion exchange column (PRP-X100, PEEK, Hamilton) were used for the separation of the total Cr (VI). The results of the determination of Cr (VI) were confirmed by the analysis of the certified reference material BCR CRM 545 (Cr (VI) in welding dust). The results obtained for the certified material (40.2±0.6 g kg(-1)) and the values recorded in the examined samples (40.7±0.6 g kg(-1)) were highly consistent. This analytical method was applied for the determination of chromium in the samples in the workplace air collected onto glass (Whatman, Ø 37 mm) and membrane filters (Sartorius, 0.8 μm, Ø 37 mm). High performance liquid chromatography with inductively coupled plasma mass spectrometry is a remarkably powerful and versatile technique for determination of chromium species in welding fume at workplace air. Crown Copyright © 2013 Published by Elsevier B.V. All rights reserved.

Planarian D-amino acid oxidase is involved in ovarian development during sexual induction.

PubMed

Maezawa, Takanobu; Tanaka, Hiroyuki; Nakagawa, Haruka; Ono, Mizuki; Aoki, Manabu; Matsumoto, Midori; Ishida, Tetsuo; Horiike, Kihachiro; Kobayashi, Kazuya

2014-05-01

To elucidate the molecular mechanisms underlying switching from asexual to sexual reproduction, namely sexual induction, we developed an assay system for sexual induction in the hermaphroditic planarian species Dugesia ryukyuensis. Ovarian development is the initial and essential step in sexual induction, and it is followed by the formation of other reproductive organs, including the testes. Here, we report a function of a planarian D-amino acid oxidase, Dr-DAO, in the control of ovarian development in planarians. Asexual worms showed significantly more widespread expression of Dr-DAO in the parenchymal space than did sexual worms. Inhibition of Dr-DAO by RNAi caused the formation of immature ovaries. In addition, we found that feeding asexual worms 5 specific D-amino acids could induce the formation of immature ovaries that are similar to those observed in Dr-DAO knockdown worms, suggesting that Dr-DAO inhibits the formation of immature ovaries by degrading these D-amino acids. Following sexual induction, Dr-DAO expression was observed in the ovaries. The knockdown of Dr-DAO during sexual induction delayed the maturation of the other reproductive organs, as well as ovary. These findings suggest that Dr-DAO acts to promote ovarian maturation and that complete sexual induction depends on the production of mature ovaries. We propose that Dr-DAO produced in somatic cells prevents the onset of sexual induction in the asexual state, and then after sexual induction, the female germ cells specifically produce Dr-DAO to induce full maturation. Therefore, Dr-DAO produced in somatic and female germline cells may play different roles in sexual induction. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Women's experiences of outpatient induction of labour with remote continuous monitoring.

PubMed

O'Brien, Ediri; Rauf, Zubair; Alfirevic, Zarko; Lavender, Tina

2013-04-01

to gain insight into women's experiences and preferences for induction in the home as part of a trial investigating the feasibility and acceptability of outpatient induction of labour with remote monitoring. a qualitative study using semi-structured individual interviews. Interview transcripts were subjected to thematic analysis to identify the dominant themes regarding women's experiences of outpatient induction. a large maternity hospital in the North West of England. fifteen women who participated in the main trial of outpatient induction of labour with remote continuous monitoring. three main themes were identified; the need for women to 'labour within their comfort zone'; their desire to achieve 'the next best thing to a normal labour' and the importance of a 'virtual presence' to offer remote reassurance. women's preference for the outpatient setting of induction of labour is dominated by their need to labour within their comfort zone. Outpatient induction offered women the familiarity and freedom of the home environment, and the resulting physical and emotional comforts helped women cope better with their labour and improved their birth experiences. While remote monitoring offered some reassurance, women still depended on effective communication from hospital staff to provide the virtual presence of a health professional in the home. the combination of slow-release prostaglandin and a remote monitoring device may provide low risk women with an improved induction and labour experience. While ongoing studies continue to explore further the safety of interventions at home, this study has importantly considered women's views and confirmed that induction at home is not only acceptable to women but also that the outpatient experience is preferable to long inpatient inductions. Copyright © 2012 Elsevier Ltd. All rights reserved.

Synaptic Synthesis, Dephosphorylation, and Degradation

PubMed Central

La Montanara, Paolo; Rusconi, Laura; Locarno, Albina; Forti, Lia; Barbiero, Isabella; Tramarin, Marco; Chandola, Chetan; Kilstrup-Nielsen, Charlotte; Landsberger, Nicoletta

2015-01-01

Mutations in the X-linked CDKL5 (cyclin-dependent kinase-like 5) gene have been associated with several forms of neurodevelopmental disorders, including atypical Rett syndrome, autism spectrum disorders, and early infantile epileptic encephalopathy. Accordingly, loss of CDKL5 in mice results in autistic-like features and impaired neuronal communication. Although the biological functions of CDKL5 remain largely unknown, recent pieces of evidence suggest that CDKL5 is involved in neuronal plasticity. Herein, we show that, at all stages of development, neuronal depolarization induces a rapid increase in CDKL5 levels, mostly mediated by extrasomatic synthesis. In young neurons, this induction is prolonged, whereas in more mature neurons, NMDA receptor stimulation induces a protein phosphatase 1-dependent dephosphorylation of CDKL5 that is mandatory for its proteasome-dependent degradation. As a corollary, neuronal activity leads to a prolonged induction of CDKL5 levels in immature neurons but to a short lasting increase of the kinase in mature neurons. Recent results demonstrate that many genes associated with autism spectrum disorders are crucial components of the activity-dependent signaling networks regulating the composition, shape, and strength of the synapse. Thus, we speculate that CDKL5 deficiency disrupts activity-dependent signaling and the consequent synapse development, maturation, and refinement. PMID:25555910

Induction of calcium-dependent nitric oxide synthases by sex hormones.

PubMed

Weiner, C P; Lizasoain, I; Baylis, S A; Knowles, R G; Charles, I G; Moncada, S

1994-05-24

We have examined the effects of pregnancy and sex hormones on calcium-dependent and calcium-independent nitric oxide synthases (NOSs) in the guinea pig. Pregnancy (near term) caused a > 4-fold increase in the activity of calcium-dependent NOS in the uterine artery and at least a doubling in the heart, kidney, skeletal muscle, esophagus, and cerebellum. The increase in NOS activity in the cerebellum during pregnancy was inhibited by the estrogen-receptor antagonist tamoxifen. Treatment with estradiol (but not progesterone) also increased calcium-dependent NOS activity in the tissues examined from both females and males. Testosterone increased calcium-dependent NOS only in the cerebellum. No significant change in calcium-independent NOS activity was observed either during pregnancy or after the administration of any sex hormone. Both pregnancy and estradiol treatment increased the amount of mRNAs for NOS isozymes eNOS and nNOS in skeletal muscle, suggesting that the increases in NOS activity result from enzyme induction. Thus both eNOS and nNOS are subject to regulation by estrogen, an action that could explain some of the changes that occur during pregnancy and some gender differences in physiology and pathophysiology.

STING-Dependent Cytosolic DNA Sensing Promotes Radiation-Induced Type I Interferon-Dependent Antitumor Immunity in Immunogenic Tumors.

PubMed

Deng, Liufu; Liang, Hua; Xu, Meng; Yang, Xuanming; Burnette, Byron; Arina, Ainhoa; Li, Xiao-Dong; Mauceri, Helena; Beckett, Michael; Darga, Thomas; Huang, Xiaona; Gajewski, Thomas F; Chen, Zhijian J; Fu, Yang-Xin; Weichselbaum, Ralph R

2014-11-20

Ionizing radiation-mediated tumor regression depends on type I interferon (IFN) and the adaptive immune response, but several pathways control I IFN induction. Here, we demonstrate that adaptor protein STING, but not MyD88, is required for type I IFN-dependent antitumor effects of radiation. In dendritic cells (DCs), STING was required for IFN-? induction in response to irradiated-tumor cells. The cytosolic DNA sensor cyclic GMP-AMP (cGAMP) synthase (cGAS) mediated sensing of irradiated-tumor cells in DCs. Moreover, STING was essential for radiation-induced adaptive immune responses, which relied on type I IFN signaling on DCs. Exogenous IFN-? treatment rescued the cross-priming by cGAS or STING-deficient DCs. Accordingly, activation of STING by a second messenger cGAMP administration enhanced antitumor immunity induced by radiation. Thus radiation-mediated antitumor immunity in immunogenic tumors requires a functional cytosolic DNA-sensing pathway and suggests that cGAMP treatment might provide a new strategy to improve radiotherapy. Copyright © 2014 Elsevier Inc. All rights reserved.

Glucocorticoid receptor activation inhibits p53-induced apoptosis of MCF10Amyc cells via induction of protein kinase Cε.

PubMed

Aziz, Moammir H; Shen, Hong; Maki, Carl G

2012-08-24

Glucocorticoid receptor (GR) is a ligand-dependent transcription factor that can promote apoptosis or survival in a cell-specific manner. Activated GR has been reported to inhibit apoptosis in mammary epithelial cells and breast cancer cells by increasing pro-survival gene expression. In this study, activated GR inhibited p53-dependent apoptosis in MCF10A cells and human mammary epithelial cells that overexpress the MYC oncogene. Specifically, GR agonists hydrocortisone or dexamethasone inhibited p53-dependent apoptosis induced by cisplatin, ionizing radiation, or the MDM2 antagonist Nutlin-3. In contrast, the GR antagonist RU486 sensitized the cells to apoptosis by these agents. Apoptosis inhibition was associated with maintenance of mitochondrial membrane potential, diminished caspase-3 and -7 activation, and increased expression at both the mRNA and protein level of the anti-apoptotic PKC family member PKCε. Knockdown of PKCε via siRNA targeting reversed the protective effect of dexamethasone and restored apoptosis sensitivity. These data provide evidence that activated GR can inhibit p53-dependent apoptosis through induction of the anti-apoptotic factor PKCε.

Dengue Virus Modulates the Unfolded Protein Response in a Time-dependent Manner*

PubMed Central

Peña, José; Harris, Eva

2011-01-01

Flaviviruses, such as dengue virus (DENV), depend on the host endoplasmic reticulum for translation, replication, and packaging of their genomes. Here we report that DENV-2 infection modulates the unfolded protein response in a time-dependent manner. We show that early DENV-2 infection triggers and then suppresses PERK-mediated eIF2α phosphorylation and that in mid and late DENV-2 infection, the IRE1-XBP1 and ATF6 pathways are activated, respectively. Activation of IRE1-XBP1 correlated with induction of downstream targets GRP78, CHOP, and GADD34. Furthermore, induction of CHOP did not induce apoptotic markers, such as suppression of anti-apoptotic protein Bcl-2, activation of caspase-9 or caspase-3, and cleavage of poly(ADP-ribose) polymerase. Finally, we show that DENV-2 replication is affected in PERK−/− and IRE1−/− mouse embryo fibroblasts when compared with wild-type mouse embryo fibroblasts. These results demonstrate that time-dependent activation of the unfolded protein response by DENV-2 can override inhibition of translation, prevent apoptosis, and prolong the viral life cycle. PMID:21385877

Lipid-induced insulin resistance mediated by the proinflammatory receptor TLR4 requires saturated fatty acid-induced ceramide biosynthesis in mice.

PubMed

Holland, William L; Bikman, Benjamin T; Wang, Li-Ping; Yuguang, Guan; Sargent, Katherine M; Bulchand, Sarada; Knotts, Trina A; Shui, Guanghou; Clegg, Deborah J; Wenk, Markus R; Pagliassotti, Michael J; Scherer, Philipp E; Summers, Scott A

2011-05-01

Obesity is associated with an enhanced inflammatory response that exacerbates insulin resistance and contributes to diabetes, atherosclerosis, and cardiovascular disease. One mechanism accounting for the increased inflammation associated with obesity is activation of the innate immune signaling pathway triggered by TLR4 recognition of saturated fatty acids, an event that is essential for lipid-induced insulin resistance. Using in vitro and in vivo systems to model lipid induction of TLR4-dependent inflammatory events in rodents, we show here that TLR4 is an upstream signaling component required for saturated fatty acid-induced ceramide biosynthesis. This increase in ceramide production was associated with the upregulation of genes driving ceramide biosynthesis, an event dependent of the activity of the proinflammatory kinase IKKβ. Importantly, increased ceramide production was not required for TLR4-dependent induction of inflammatory cytokines, but it was essential for TLR4-dependent insulin resistance. These findings suggest that sphingolipids such as ceramide might be key components of the signaling networks that link lipid-induced inflammatory pathways to the antagonism of insulin action that contributes to diabetes.

Temperature dependence of protein solubility-determination, application to crystallization, and growth kinetics studies

NASA Technical Reports Server (NTRS)

Rosenberger, Franz

1993-01-01

A scintillation method was developed for determinations of the temperature dependence of the solubility, and of nucleation induction times of proteins, in 50-100 mu(l) volumes of solution. Solubility data for lysozyme and horse serum albumin were obtained for various combinations of pH and precipitant concentrations. These data and the nucleation induction information were used for dynamic crystallization control, that is, for the controlled separation of nucleation and growth stages. Individual lysozyme and horse serum albumin crystals were grown in 15-20 mu(l) solution volumes contained in x-ray capillaries. The morphology and kinetics of the growth and dissolution of lysozyme in aqueous solutions with 2.5 percent NaCl and at pH = 4.5 was studied in situ with a depth resolution of 300 A (4 unit cells) by high resolution optical microscopy and digital image processing. The bulk super- or under saturation, sigma, of the solution inside a closed growth cell was controlled by temperature. The growth habit was bound by (110) and (101) faces that grew through layer spreading, although with different growth rate dependencies on supersaturation/temperature. At sigma less than 10 (obtained at higher temperatures) growth was purely kinetic ally controlled, with impurity effects (macrostep formation and kinetic hindrance) becoming significant for sigma less than 2. At sigma greater than 10 (lower temperatures), anisotropies in the interfacial kinetics were more pronounced, with interfacial kinetics and bulk transport becoming equally important to the growth morphology. Growth rates were growth history dependent. The formation of striations (layers of irregularly incorporated solution) was unambiguously correlated with growth temperature variations. Etching exposed dislocations and various high-index faces whose growth morphologies were studied during return to the steady state growth form. Growth steps were observed to originate from two-dimensional nuclei or from outcrops of growth striations, and from dislocations that preferentially formed in growth sector boundaries.

CpG-B Oligodeoxynucleotides Inhibit TLR-Dependent and -Independent Induction of Type I IFN in Dendritic Cells

PubMed Central

Liu, Yi C.; Gray, Reginald C.; Hardy, Gareth A. D.; Kuchtey, John; Abbott, Derek W.; Emancipator, Steven N.; Harding, Clifford V.

2010-01-01

CpG oligodeoxynucleotides (ODNs) signal through TLR9 to induce type I IFN (IFN-αβ) in dendritic cells (DCs). CpG-A ODNs are more efficacious than CpG-B ODNs for induction of IFN-αβ. Because IFN-αβ may contribute to autoimmunity, it is important to identify mechanisms to inhibit induction of IFN-αβ. In our studies, CpG-B ODN inhibited induction of IFN-αβ by CpG-A ODN, whereas induction of TNF-α and IL-12p40 by CpG-A ODN was not affected. CpG-B inhibition of IFN-αβ was observed in FLT3 ligand-induced murine DCs, purified murine myeloid DCs, plasmacytoid DCs, and human PBMCs. CpG-B ODN inhibited induction of IFN-αβ by agonists of multiple receptors, including MyD88-dependent TLRs (CpG-AODN signaling via TLR9, or R837 or Sendai virus signaling via TLR7) and MyD88-independent receptors (polyinosinic:polycytidylic acid signaling via TLR3 or ds break-DNA signaling via a cytosolic pathway). CpG-B ODN did not inhibit the IFN-αβ positive feedback loop second-wave IFN-αβ, because IFN-αβ–induced expression of IFN-αβ was unaffected, and CpG-B inhibition of IFN-αβ was manifested in IFN-αβR−/− DCs, which lack the positive feedback mechanism. Rather, CpG-B ODN inhibited early TLR-induced first wave IFN-α4 and IFN-β. Chromatin immunoprecipitation revealed that association of IFN regulatory factor 1 with the IFN-α4 and IFN-β promoters was induced by CpG-A ODN but not CpG-B ODN. Moreover, CpG-A–induced association of IFN regulatory factor 1 with these promoters was inhibited by CpG-B ODN. Our studies demonstrate a novel mechanism of transcriptional regulation of first-wave IFN-αβ that selectively inhibits induction of IFN-αβ downstream of multiple receptors and may provide targets for future therapeutic inhibition of IFN-αβ expression in vivo. PMID:20181884

Carprofen induction of p75NTR-dependent apoptosis via the p38 mitogen-activated protein kinase pathway in prostate cancer cells.

PubMed

Khwaja, Fatima S; Quann, Emily J; Pattabiraman, Nagarajan; Wynne, Shehla; Djakiew, Daniel

2008-11-01

The p75 neurotrophin receptor (p75(NTR)) functions as a tumor suppressor in prostate epithelial cells, where its expression declines with progression to malignant cancer. Previously, we showed that treatment with R-flurbiprofen or ibuprofen induced p75(NTR) expression in several prostate cancer cell lines leading to p75(NTR)-mediated decreased survival. Using the 2-phenyl propionic acid moiety of these profens as a pharmacophore, we screened an in silico database of 30 million compounds and identified carprofen as having an order of magnitude greater activity for induction of p75(NTR) levels and inhibition of cell survival. Prostate (PC-3 and DU-145) and bladder (T24) cancer cells were more sensitive to carprofen induction of p75(NTR)-associated loss of survival than breast (MCF-7) and fibroblast (3T3) cells. Transfection of prostate cell lines with a dominant-negative form of p75(NTR) before carprofen treatment partially rescued cell survival, showing a cause-and-effect relationship between carprofen induction of p75(NTR) levels and inhibition of survival. Carprofen induced apoptotic nuclear fragmentation in prostate but not in MCF-7 and 3T3 cells. Furthermore, small interfering RNA knockdown of the p38 mitogen-activated protein kinase (MAPK) protein prevented induction of p75(NTR) by carprofen in both prostate cell lines. Carprofen treatment induced phosphorylation of p38 MAPK as early as within 1 min. Expression of a dominant-negative form of MK2, the kinase downstream of p38 MAPK frequently associated with signaling cascades leading to apoptosis, prevented carprofen induction of the p75(NTR) protein. Collectively, we identify carprofen as a highly potent profen capable of inducing p75(NTR)-dependent apoptosis via the p38 MAPK pathway in prostate cancer cells.

Assessment of the Practicum by Students from the Perspective of the Induction Process

ERIC Educational Resources Information Center

Pacios, Ana R.

2013-01-01

This article shows the assessments made by students from the Carlos III University of Madrid of the induction period in the practicum they performed during their courses of study, and their perceptions of and attitudes towards it. The method used was a survey comprising 6 questions about the induction process, which was carried out among 359…

How Induction Programs Affect the Decision of Alternate Route Urban Teachers to Remain Teaching

ERIC Educational Resources Information Center

LoCascio, Steven J.; Smeaton, Patricia S.; Waters, Faith H.

2016-01-01

This mixed-methods study analyzes the induction programs for alternate route beginning teachers in low socioeconomic, urban schools. The researcher surveyed 53 teachers at the end of their first year and conducted six in-depth follow-up interviews. The study found that half the teachers did not receive an induction program congruent with state…

Supporting First Year Alternatively Certified Urban and Rural Intern Teachers through a Multicomponent Distance Induction Program

ERIC Educational Resources Information Center

Gresko, Jennifer A.

2013-01-01

The pathway for entering the K-12 classroom as a teacher varies compared to what was once the traditional model of teacher preparation. In this mixed-methods action research study, I explore supporting first year alternatively certified urban and rural intern teachers through a multicomponent distance induction program. The induction model in this…

A Drive Method for Small Inductance PM Motor Under No-Load Condition

NASA Astrophysics Data System (ADS)

Tanaka, Daisuke; Ohishi, Kiyoshi

The harmonic wave of the exciting current of the motor is generated by the pulsewidth modulated voltage of the inverter. The motors that have low inpedance genetate more harmonics and make larger iron loss. This paper describes an implementation of drive control for a small inductance permanent-magnet motor drive. A comparative experiment has been carried out with conventional methods and the utility of the proposed method has been verified.

Temporal aspects of tumorigenic response to individual and mixed carcinogens. Comprehensive progress report, June 1, 1975--May 31, 1978. [Mouse skin, rats, hamsters

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

Albert, R.E.; Burns, F.J.; Altshuler, B.

1978-02-01

The research proposed here is designed to obtain a better understanding of the temporal kinetics of tumor induction when one or more carcinogens are present simultaneously or sequentially for prolonged periods of time. Studies done to date under this contract have shown that carcinogenesis in mouse skin by polycyclic aromatic hydrocarbon carcinogens is consistent with the induction of dependent and autonomous cell transformations by the carcinogen followed by the conversion of autonomous tumor cells into malignancies at a rate which is determined by the level of carcinogen exposure. Dependent cell transformations remain latent in the skin unless expressed by amore » promoting agent. Dependent neoplasia appears to follow one-hit kinetics while malignancy is a multihit endpoint. Dose-related and time-related aspects of tumor induction are separable in the initiation-promotion system of mouse skin which along with rat skin and hamster lung is being used as a model for testing hypotheses. Results to date provide the basis for a new interpretation of the linear non-threshold extrapolation model. The broad aim of the study is to provide a basis or rationale for estimating risks associated with prolonged exposures to carcinogens found in the environment and to predict how different tissues and species respond to the same carcinogens.« less

The response of Hordeum spontaneum desert ecotype to drought and excessive light intensity is characterized by induction of O2 dependent photochemical activity and anthocyanin accumulation.

PubMed

Eppel, Amir; Keren, Nir; Salomon, Eitan; Volis, Sergei; Rachmilevitch, Shimon

2013-03-01

The goal of the current research was to study the role of anthocyanin accumulation, O(2)-related photochemical processes and non-photochemical quenching (NPQ) in the response of desert and Mediterranean plants to drought and excessive light. Plants of Hordeum spontaneum were collected from Mediterranean and desert environments and were subjected to terminal drought for 25 days and then measured for PSII yield at 2 and 21% O(2), NPQ, net carbon assimilation, stomatal conductance, leaf relative water content (LRWC), anthocyanin concentration and leaf absorbance. Under terminal drought, LRWC, carbon assimilation and stomatal conductance decreased similarly and significantly in both the Mediterranean and the desert ecotypes. Anthocyanin accumulated more in the desert ecotype than in the Mediterranean ecotype. NPQ increased more in the Mediterranean ecotype as compared with the desert ecotype. PSII yield decreased significantly in the Mediterranean ecotype under drought and was much lower than in the desert ecotype under drought. The relatively high PSII yield under drought in the desert ecotype was O(2) dependent. The response of the H. spontaneum ecotype from a desert environment to drought stress was characterized by anthocyanin accumulation and induction of O(2) dependent photochemical activity, while the response of the Mediterranean ecotype was based on a higher induction of NPQ. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Regulated overexpression of interleukin 11 in the lung. Use to dissociate development-dependent and -independent phenotypes.

PubMed Central

Ray, P; Tang, W; Wang, P; Homer, R; Kuhn, C; Flavell, R A; Elias, J A

1997-01-01

Standard overexpression transgenic approaches are limited in their ability to model waxing and waning diseases and frequently superimpose development-dependent and -independent phenotypic manifestations. We used the clara cell 10-kD protein (CC10) promoter and the reverse tetracycline transactivator (rtTA) to create a lung-specific, externally regulatable, overexpression transgenic system and used this system to express human interleukin 11 (IL-11) in respiratory structures. Gene induction could be achieved in utero, in neonates and in adult animals. Moreover, gene expression could be turned off by removal of the inducing stimulus. When gene activation was initiated in utero and continued into adulthood, subepithelial airway fibrosis, peribronchiolar mononuclear nodules, and alveolar enlargement (emphysema) were noted. Induction in the mature lung caused airway remodeling and peribronchiolar nodules, but alveolar enlargement was not appreciated. In contrast, induction in utero and during the first 14 d of life caused alveolar enlargement without airway remodeling or peribronchiolar nodules. Thus, IL-11 overexpression causes abnormalities that are dependent (large alveoli) and independent (airway remodeling, peribronchiolar nodules) of lung growth and development, and the CC10-rtTA system can be used to differentiate among these effector functions. The CC10-rtTA transgenic system can be used to model waxing and waning, childhood and growth and development-related biologic processes with enhanced fidelity. PMID:9366564

Drug Craving Terminology among Opiate Dependents; A Mixed Method Study

PubMed Central

Maarefvand, Masoomeh; Ghiasvand, Hamid Reza

2013-01-01

Objective Drug craving is defined as an urge to continue substance abuse. Drug dependents use different terms to express their subjective feeling of craving. This study was an attempt to generate an understanding of craving terminology among different groups of Persian speaking Iranian opiate dependents. Method Terms used for the meaning of drug craving were listed by 36 ex-opiate dependents in focus group discussion meetings in the first phase of the study. These terms were composed from Craving Terms Questionnaire. In the second phase, 120 subjects in 3 groups of opiate dependents and a group of Current Opiate Abusers rated usage frequency of each term in the questionnaire under a Twelve-Step Program, Methadone Maintenance, and Other Abstinence-based Programs. Results Eighty nine terms were categorized in stimulation and triggering, attention bias and obsession, decision making difficulty, information processing impairment, withdrawal induction, drug euphoric experience, mental urge, motor control problem, negative valancing and stigmatizing. Terms for the three categories of mental urge, attention bias and obsession and motor control problem were used more than others. Patients in Methadone Maintenance Treatment (MMT) group used different categories of craving terms in comparison to other groups. Abstinent cases reported higher total score for craving terms in comparison to other groups in Twelve-Step Program and other abstinence-based programs. Conclusion Each craving-related term is associated with some aspects of the multidimensional concept of craving. A drug-craving thesaurus could provide a better understanding of craving nature from a drug dependent point of view. There are differences among abstinence vs. maintenance based treated opiate dependents in using craving terms. Addiction therapists will benefit from accessing drug dependents’ lexicon to assess and create therapeutic alliance with their clients. PMID:24130609

Pure non-dioxin-like PCB congeners suppress induction of AhR-dependent endpoints in rat liver cells.

PubMed

Brenerová, Petra; Hamers, Timo; Kamstra, Jorke H; Vondráček, Jan; Strapáčová, Simona; Andersson, Patrik L; Machala, Miroslav

2016-02-01

The relative potencies of non-ortho-substituted coplanar polychlorinated biphenyl (PCB) congeners to activate the aryl hydrocarbon receptor (AhR) and to cause the AhR-dependent toxic events are essential for their risk assessment. Since some studies suggested that abundant non-dioxin-like PCB congeners (NDL-PCBs) may alter the AhR activation by PCB mixtures and possibly cause non-additive effects, we evaluated potential suppressive effects of NDL-PCBs on AhR activation, using a series of 24 highly purified NDL-PCBs. We investigated their impact on the model AhR agonist-induced luciferase reporter gene expression in rat hepatoma cells and on induction of CYP1A1/1B1 mRNAs and deregulation of AhR-dependent cell proliferation in rat liver epithelial cells. PCBs 128, 138, and 170 significantly suppressed AhR activation (with IC50 values from 1.4 to 5.6 μM), followed by PCBs 28, 47, 52, and 180; additionally, PCBs 122, 153, and 168 showed low but still significant potency to reduce luciferase activity. Detection of CYP1A1 mRNA levels in liver epithelial cells largely confirmed these results for the most abundant NDL-PCBs, whereas the other AhR-dependent events (CYP1B1 mRNA expression, induction of cell proliferation in confluent cells) were less sensitive to NDL-PCBs, thus indicating a more complex regulation of these endpoints. The present data suggest that some NDL-PCBs could modulate overall dioxin-like effects in complex mixtures.

The difference in LET and ion species dependence for induction of initially measured and non-rejoined chromatin breaks in normal human fibroblasts.

PubMed

Tsuruoka, Chizuru; Suzuki, Masao; Hande, M Prakash; Furusawa, Yoshiya; Anzai, Kazunori; Okayasu, Ryuichi

2008-08-01

We studied the LET and ion species dependence of the induction of chromatin breaks measured immediately after irradiation as initially measured breaks and after 24 h postirradiation incubation (37 degrees C) as non-rejoined breaks in normal human fibroblasts with different heavy ions, such as carbon, neon, silicon and iron, generated by the Heavy Ion Medical Accelerator in Chiba (HIMAC) at the National Institute of Radiological Science (NIRS). Chromatin breaks were measured as an excess number of fragments of prematurely condensed chromosomes using premature chromosome condensation (PCC). The results showed that the number of excess fragments per cell per Gy for initially measured chromatin breaks was dependent on LET in the range from 13.3 to 113.1 keV/mum but was not dependent on ion species. On the other hand, the number of non-rejoined chromatin breaks detected after 24 h postirradiation incubation was clearly dependent on both LET and ion species. No significant difference was observed in the cross section for initially measured breaks, but a statistically significant difference was observed in the cross section for non-rejoined breaks among carbon, neon, silicon and iron ions. This suggests that the LET-dependent structure in the biological effects is reflected in biological consequences of repair processes.

Biotransformation and induction: implications for toxicity, bioaccumulation and monitoring of environmental xenobiotics in fish.

PubMed Central

Kleinow, K M; Melancon, M J; Lech, J J

1987-01-01

Biotransformation of xenobiotics in fish occurs by many of the same reactions as in mammals. These reactions have been shown to affect the bioaccumulation, persistence, residue dynamics, and toxicity of select chemicals in fish. P-450-dependent monooxygenase activity of fish can be induced by polycyclic aromatic hydrocarbons, but phenobarbital-type agents induce poorly, if at all. Fish monooxygenase activity exhibits ideal temperature compensation and sex-related variation. Induction of monooxygenase activity by polycyclic aromatic hydrocarbons can result in qualitative as well as quantitative changes in the metabolic profile of a chemical. Induction can also alter toxicity. In addition, multiple P-450 isozymes have been described for several fish species. The biotransformation products of certain chemicals have been related to specific P-450 isozymes, and the formation of these products can be influenced by induction. Exposure of fish to low levels of certain environmental contaminants has resulted in induction of specific monooxygenase activities and monitoring of such activities has been suggested as a means of identifying areas of pollutant exposure in the wild. PMID:3297653

Interactive Effects of Jasmonic Acid, Salicylic Acid, and Gibberellin on Induction of Trichomes in Arabidopsis1

PubMed Central

Traw, M. Brian; Bergelson, Joy

2003-01-01

Leaf trichomes protect plants from attack by insect herbivores and are often induced following damage. Hormonal regulation of this plant induction response has not been previously studied. In a series of experiments, we addressed the effects of artificial damage, jasmonic acid, salicylic acid, and gibberellin on induction of trichomes in Arabidopsis. Artificial damage and jasmonic acid caused significant increases in trichome production of leaves. The jar1-1 mutant exhibited normal trichome induction following treatment with jasmonic acid, suggesting that adenylation of jasmonic acid is not necessary. Salicylic acid had a negative effect on trichome production and consistently reduced the effect of jasmonic acid, suggesting negative cross-talk between the jasmonate and salicylate-dependent defense pathways. Interestingly, the effect of salicylic acid persisted in the nim1-1 mutant, suggesting that the Npr1/Nim1 gene is not downstream of salicylic acid in the negative regulation of trichome production. Last, we found that gibberellin and jasmonic acid had a synergistic effect on the induction of trichomes, suggesting important interactions between these two compounds. PMID:14551332

Ammonia synthesis using magnetic induction method (MIM)

NASA Astrophysics Data System (ADS)

Puspitasari, P.; Razak, J. Abd; Yahya, N.

2012-09-01

The most challenging issues for ammonia synthesis is to get the high yield. New approach of ammonia synthesis by using Magnetic Induction Method (MIM) and the Helmholtz Coils has been proposed. The ammonia detection was done by using Kjeldahl Method and FTIR. The system was designed by using Autocad software. The magnetic field of MIM was vary from 100mT-200mT and the magnetic field for the Helmholtz coils was 14mT. The FTIR result shows that ammonia has been successfully formed at stretching peaks 1097,1119,1162,1236, 1377, and 1464 cm-1. UV-VIS result shows the ammonia bond at 195nm of wavelength. The ammonia yield was increase to 244.72μmole/g.h by using the MIM and six pairs of Helmholtz coils. Therefore this new method will be a new promising method to achieve the high yield ammonia at ambient condition (at 25δC and 1atm), under the Magnetic Induction Method (MIM).

Numerical simulation of inductive method for determining spatial distribution of critical current density

NASA Astrophysics Data System (ADS)

Kamitani, A.; Takayama, T.; Tanaka, A.; Ikuno, S.

2010-11-01

The inductive method for measuring the critical current density jC in a high-temperature superconducting (HTS) thin film has been investigated numerically. In order to simulate the method, a non-axisymmetric numerical code has been developed for analyzing the time evolution of the shielding current density. In the code, the governing equation of the shielding current density is spatially discretized with the finite element method and the resulting first-order ordinary differential system is solved by using the 5th-order Runge-Kutta method with an adaptive step-size control algorithm. By using the code, the threshold current IT is evaluated for various positions of a coil. The results of computations show that, near a film edge, the accuracy of the estimating formula for jC is remarkably degraded. Moreover, even the proportional relationship between jC and IT will be lost there. Hence, the critical current density near a film edge cannot be estimated by using the inductive method.

Numerical simulations of induction and MWD logging tools and data inversion method with X-window interface on a UNIX workstation

NASA Astrophysics Data System (ADS)

Tian, Xiang-Dong

The purpose of this research is to simulate induction and measuring-while-drilling (MWD) logs. In simulation of logs, there are two tasks. The first task, the forward modeling procedure, is to compute the logs from known formation. The second task, the inversion procedure, is to determine the unknown properties of the formation from the measured field logs. In general, the inversion procedure requires the solution of a forward model. In this study, a stable numerical method to simulate induction and MWD logs is presented. The proposed algorithm is based on a horizontal eigenmode expansion method. Vertical propagation of modes is modeled by a three-layer module. The multilayer cases are treated as a cascade of these modules. The mode tracing algorithm possesses stable characteristics that are superior to other methods. This method is applied to simulate the logs in the formations with both vertical and horizontal layers, and also used to study the groove effects of the MWD tool. The results are very good. Two-dimensional inversion of induction logs is an nonlinear problem. Nonlinear functions of the apparent conductivity are expanded into a Taylor series. After truncating the high order terms in this Taylor series, the nonlinear functions are linearized. An iterative procedure is then devised to solve the inversion problem. In each iteration, the Jacobian matrix is calculated, and a small variation computed using the least-squares method is used to modify the background medium. Finally, the inverted medium is obtained. The horizontal eigenstate method is used to solve the forward problem. It is found that a good inverted formation can be obtained by using measurements. In order to help the user simulate the induction logs conveniently, a Wellog Simulator, based on the X-window system, is developed. The application software (FORTRAN codes) embedded in the Simulator is designed to simulate the responses of the induction tools in the layered formation with dipping beds. The graphic user-interface part of the Wellog Simulator is implemented with C and Motif. Through the user interface, the user can prepare the simulation data, select the tools, simulate the logs and plot the results.

High-Precision Hysteresis Sensing of the Quartz Crystal Inductance-to-Frequency Converter

PubMed Central

Matko, Vojko; Milanović, Miro

2016-01-01

A new method for the automated measurement of the hysteresis of the temperature-compensated inductance-to-frequency converter with a single quartz crystal is proposed. The new idea behind this method is a converter with two programmable analog switches enabling the automated measurement of the converter hysteresis, as well as the temperature compensation of the quartz crystal and any other circuit element. Also used is the programmable timing control device that allows the selection of different oscillating frequencies. In the proposed programmable method two different inductances connected in series to the quartz crystal are switched in a short time sequence, compensating the crystal’s natural temperature characteristics (in the temperature range between 0 and 50 °C). The procedure allows for the measurement of the converter hysteresis at various values of capacitance connected in parallel with the quartz crystal for the converter sensitivity setting at selected inductance. It, furthermore, enables the measurement of hysteresis at various values of inductance at selected parallel capacitance (sensitivity) connected to the quartz crystal. The article shows that the proposed hysteresis measurement of the converter, which converts the inductance in the range between 95 and 100 μH to a frequency in the range between 1 and 200 kHz, has only 7 × 10−13 frequency instability (during the temperature change between 0 and 50 °C) with a maximum 1 × 10−11 hysteresis frequency difference. PMID:27367688

Determination of Magnetic Parameters of Maghemite (γ-Fe2O3) Core-Shell Nanoparticles from Nonlinear Magnetic Susceptibility Measurements

NASA Astrophysics Data System (ADS)

Syvorotka, Ihor I.; Pavlyk, Lyubomyr P.; Ubizskii, Sergii B.; Buryy, Oleg A.; Savytskyy, Hrygoriy V.; Mitina, Nataliya Y.; Zaichenko, Oleksandr S.

2017-04-01

Method of determining of magnetic moment and size from measurements of dependence of the nonlinear magnetic susceptibility upon magnetic field is proposed, substantiated and tested for superparamagnetic nanoparticles (SPNP) of the "magnetic core-polymer shell" type which are widely used in biomedical technologies. The model of the induction response of the SPNP ensemble on the combined action of the magnetic harmonic excitation field and permanent bias field is built, and the analysis of possible ways to determine the magnetic moment and size of the nanoparticles as well as the parameters of the distribution of these variables is performed. Experimental verification of the proposed method was implemented on samples of SPNP with maghemite core in dry form as well as in colloidal systems. The results have been compared with the data obtained by other methods. Advantages of the proposed method are analyzed and discussed, particularly in terms of its suitability for routine express testing of SPNP for biomedical technology.

The Gene Regulatory Network of Lens Induction Is Wired through Meis-Dependent Shadow Enhancers of Pax6

PubMed Central

Antosova, Barbora; Smolikova, Jana; Klimova, Lucie; Lachova, Jitka; Bendova, Michaela; Kozmikova, Iryna; Machon, Ondrej; Kozmik, Zbynek

2016-01-01

Lens induction is a classical developmental model allowing investigation of cell specification, spatiotemporal control of gene expression, as well as how transcription factors are integrated into highly complex gene regulatory networks (GRNs). Pax6 represents a key node in the gene regulatory network governing mammalian lens induction. Meis1 and Meis2 homeoproteins are considered as essential upstream regulators of Pax6 during lens morphogenesis based on their interaction with the ectoderm enhancer (EE) located upstream of Pax6 transcription start site. Despite this generally accepted regulatory pathway, Meis1-, Meis2- and EE-deficient mice have surprisingly mild eye phenotypes at placodal stage of lens development. Here, we show that simultaneous deletion of Meis1 and Meis2 in presumptive lens ectoderm results in arrested lens development in the pre-placodal stage, and neither lens placode nor lens is formed. We found that in the presumptive lens ectoderm of Meis1/Meis2 deficient embryos Pax6 expression is absent. We demonstrate using chromatin immunoprecipitation (ChIP) that in addition to EE, Meis homeoproteins bind to a remote, ultraconserved SIMO enhancer of Pax6. We further show, using in vivo gene reporter analyses, that the lens-specific activity of SIMO enhancer is dependent on the presence of three Meis binding sites, phylogenetically conserved from man to zebrafish. Genetic ablation of EE and SIMO enhancers demostrates their requirement for lens induction and uncovers an apparent redundancy at early stages of lens development. These findings identify a genetic requirement for Meis1 and Meis2 during the early steps of mammalian eye development. Moreover, they reveal an apparent robustness in the gene regulatory mechanism whereby two independent "shadow enhancers" maintain critical levels of a dosage-sensitive gene, Pax6, during lens induction. PMID:27918583

Pyrethroid insecticides: Isoform-dependent hydrolysis, induction of cytochrome P450 3A4 and evidence on the involvement of the pregnane X receptor

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

Yang Dongfang; Wang Xiliang; Chen Yitzai

2009-05-15

Pyrethroids account for more than one-third of the insecticides currently marketed in the world. In mammals, these insecticides undergo extensive metabolism by carboxylesterases and cytochrome P450s (CYPs). In addition, some pyrethroids are found to induce the expression of CYPs. The aim of this study was to determine whether pyrethroids induce carboxylesterases and CYP3A4, and whether the induction is correlated inversely with their hydrolysis. Human liver microsomes were pooled and tested for the hydrolysis of 11 pyrethroids. All pyrethroids were hydrolyzed by the pooled microsomes, but the hydrolytic rates varied by as many as 14 fold. Some pyrethroids such as bioresmethrinmore » were preferably hydrolyzed by carboxylesterase HCE1, whereas others such as bifenthrin preferably by HCE2. In primary human hepatocytes, all pyrethroids except tetramethrin significantly induced CYP3A4. In contrast, insignificant changes were detected on the expression of carboxylesterases. The induction of CYP3A4 was confirmed in multiple cell lines including HepG2, Hop92 and LS180. Overall, the magnitude of the induction was correlated inversely with the rates of hydrolysis, but positively with the activation of the pregnane X receptor (PXR). Transfection of a carboxylesterase markedly decreased the activation of PXR, and the decrease was in agreement with carboxylesterase-based preference for hydrolysis. In addition, human PXR variants as well as rat PXR differed from human PXR (wild-type) in responding to certain pyrethroids (e.g., lambda-cyhalothrin), suggesting that induction of PXR target genes by these pyrethroids varies depending on polymorphic variants and the PXR species identity.« less

PYRETHROID INSECTICIDES: ISOFORM-DEPENDENT HYDROLYSIS, INDUCTION OF CYTOCHROME P450 3A4 AND EVIDENCE ON THE INVOLVEMENT OF THE PREGNANE X RECEPTOR

PubMed Central

Yang, Dongfang; Wang, Xiliang; Chen, Yi-tzai; Deng, Ruitang; Yan, Bingfang

2009-01-01

Pyrethroids account for more than one-third of the insecticides currently marketed in the world. In mammals, these insecticides undergo extensive metabolism by carboxylesterases and cytochrome P450s (CYPs). In addition, some pyrethroids are found to induce the expression of CYPs. The aim of this study was to determine whether pyrethroids induce carboxylesterases and CYP3A4, and whether the induction is correlated inversely with their hydrolysis. Human liver microsomes were pooled and tested for the hydrolysis of 11 pyrethroids. All pyrethroids were hydrolyzed by the pooled microsomes, but the hydrolytic rates varied by as many as 14 fold. Some pyrethroids such as bioresmethrin were preferably hydrolyzed by carboxylesterase HCE1, whereas others such as bifenthrin preferably by HCE2. In primary human hepatocytes, all pyrethroids except tetramethrin significantly induced CYP3A4. In contrast, insignificant changes were detected on the expression of carboxylesterases. The induction of CYP3A4 was confirmed in multiple cell lines including HepG2, Hop92 and LS180. Overall, the magnitude of the induction was correlated inversely with the rates of hydrolysis, but positively with the activation of the pregnane X receptor (PXR). Transfection of a carboxylesterase markedly decreased the activation of PXR, and the decrease was in agreement with carboxylesterase-based preference for hydrolysis. In addition, human PXR variants as well as rat PXR differed from human PXR (wild-type) in responding to certain pyrethroids (e.g., lambda-cyhalothrin), suggesting that induction of PXR target genes by these pyrethroids varies depending on polymorphic variants and the PXR species identity. PMID:19249324

Pyrethroid insecticides: isoform-dependent hydrolysis, induction of cytochrome P450 3A4 and evidence on the involvement of the pregnane X receptor.

PubMed

Yang, Dongfang; Wang, Xiliang; Chen, Yi-Tzai; Deng, Ruitang; Yan, Bingfang

2009-05-15

Pyrethroids account for more than one-third of the insecticides currently marketed in the world. In mammals, these insecticides undergo extensive metabolism by carboxylesterases and cytochrome P450s (CYPs). In addition, some pyrethroids are found to induce the expression of CYPs. The aim of this study was to determine whether pyrethroids induce carboxylesterases and CYP3A4, and whether the induction is correlated inversely with their hydrolysis. Human liver microsomes were pooled and tested for the hydrolysis of 11 pyrethroids. All pyrethroids were hydrolyzed by the pooled microsomes, but the hydrolytic rates varied by as many as 14 fold. Some pyrethroids such as bioresmethrin were preferably hydrolyzed by carboxylesterase HCE1, whereas others such as bifenthrin preferably by HCE2. In primary human hepatocytes, all pyrethroids except tetramethrin significantly induced CYP3A4. In contrast, insignificant changes were detected on the expression of carboxylesterases. The induction of CYP3A4 was confirmed in multiple cell lines including HepG2, Hop92 and LS180. Overall, the magnitude of the induction was correlated inversely with the rates of hydrolysis, but positively with the activation of the pregnane X receptor (PXR). Transfection of a carboxylesterase markedly decreased the activation of PXR, and the decrease was in agreement with carboxylesterase-based preference for hydrolysis. In addition, human PXR variants as well as rat PXR differed from human PXR (wild-type) in responding to certain pyrethroids (e.g., lambda-cyhalothrin), suggesting that induction of PXR target genes by these pyrethroids varies depending on polymorphic variants and the PXR species identity.

Microwave Properties of Superconductors Close to the Superconductor-Insulator Transition.

PubMed

Feigel'man, M V; Ioffe, L B

2018-01-19

Strongly disordered pseudogapped superconductors are expected to display arbitrarily high values of kinetic inductance close to the superconductor-insulator transition (SIT), which make them attractive for the implementation of large dissipationless inductance. We develop the theory of the collective modes in these superconductors and discuss associated dissipation at microwave frequencies. We obtain the collective mode spectra dependence on the disorder level and conclude that collective modes become a relevant source of dissipation and noise in the outer proximity of the SIT.

Microwave Properties of Superconductors Close to the Superconductor-Insulator Transition

NASA Astrophysics Data System (ADS)

Feigel'man, M. V.; Ioffe, L. B.

2018-01-01

Strongly disordered pseudogapped superconductors are expected to display arbitrarily high values of kinetic inductance close to the superconductor-insulator transition (SIT), which make them attractive for the implementation of large dissipationless inductance. We develop the theory of the collective modes in these superconductors and discuss associated dissipation at microwave frequencies. We obtain the collective mode spectra dependence on the disorder level and conclude that collective modes become a relevant source of dissipation and noise in the outer proximity of the SIT.

Reduction in resource use with the misoprostol vaginal insert vs the dinoprostone vaginal insert for labour induction: a model-based analysis from a United Kingdom healthcare perspective.

PubMed

Draycott, T; van der Nelson, H; Montouchet, C; Ruff, L; Andersson, F

2016-02-10

In view of the increasing pressure on the UK's maternity units, new methods of labour induction are required to alleviate the burden on the National Health Service, while maintaining the quality of care for women during delivery. A model was developed to evaluate the resource use associated with misoprostol vaginal inserts (MVIs) and dinoprostone vaginal inserts (DVIs) for the induction of labour at term. The one-year Markov model estimated clinical outcomes in a hypothetical cohort of 1397 pregnant women (parous and nulliparous) induced with either MVI or DVI at Southmead Hospital, Bristol, UK. Efficacy and safety data were based on published and unpublished results from a phase III, double-blind, multicentre, randomised controlled trial. Resource use was modelled using data from labour induction during antenatal admission to patient discharge from Southmead Hospital. The model's sensitivity to key parameters was explored in deterministic multi-way and scenario-based analyses. Over one year, the model results indicated MVI use could lead to a reduction of 10,201 h (28.9%) in the time to vaginal delivery, and an increase of 121% and 52% in the proportion of women achieving vaginal delivery at 12 and 24 h, respectively, compared with DVI use. Inducing women with the MVI could lead to a 25.2% reduction in the number of midwife shifts spent managing labour induction and 451 fewer hospital bed days. These resource utilisation reductions may equate to a potential 27.4% increase in birthing capacity at Southmead Hospital, when using the MVI instead of the DVI. Resource use, in addition to clinical considerations, should be considered when making decisions about labour induction methods. Our model analysis suggests the MVI is an effective method for labour induction, and could lead to a considerable reduction in resource use compared with the DVI, thereby alleviating the increasing burden of labour induction in UK hospitals.

First-order chiral to non-chiral transition in the angular dependence of the upper critical induction of the Scharnberg-Klemm p-wave pair state

NASA Astrophysics Data System (ADS)

Klemm, Richard; Zhang, Jingchuan; Lorscher, Christopher; Gu, Qiang

2014-03-01

We calculate the temperature T and angular (θ , ϕ) dependence of the upper critical induction Bc 2(θ , ϕ , T) for parallel-spin superconductors with an axially symmetric p-wave pairing interaction pinned to the lattice and a dominant ellipsoidal Fermi surface (FS). When both parallel-spin states are allowed, the chiral Scharnberg-Klemm state Bc 2(θ , ϕ , T) exceeds that of the chiral Anderson-Brinkman-Morel state for all FS anisotropies, and exhibits a kink at θ =θ*(T , ϕ) , indicative of a first-order transition from its chiral, nodal-direction behavior to its non-chiral, antinodal-direction behavior. Potential applicability to Sr2RuO4, UCoGe, and topological superconductors is discussed.

Neutron flux spectrum revealed by Nb-based current-biased kinetic inductance detector with a 10B conversion layer

NASA Astrophysics Data System (ADS)

Miyajima, Shigeyuki; Shishido, Hiroaki; Narukami, Yoshito; Yoshioka, Naohito; Fujimaki, Akira; Hidaka, Mutsuo; Oikawa, Kenichi; Harada, Masahide; Oku, Takayuki; Arai, Masatoshi; Ishida, Takekazu

2017-01-01

We successfully derived the time-dependent flux of pulsed neutrons using a superconducting Nb-based current-biased kinetic inductance detector (CB-KID) with a 10B conversion layer at Japan Proton Accelerator Research Complex. Our CB-KID is a meander line made of a 40-nm-thick Nb thin film with 1 - μm line width, which is covered with a 150-nm-thick 10B conversion layer. The detector works at a temperature below 4 K. The evaluated detection efficiency of the CB-KID in this experiment is 0.23 % at the neutron energy of 25.4 meV. The time-dependent flux spectra of pulsed neutrons thus obtained are in good agreement with the results obtained by the Monte Carlo simulations.

Breaking through "The Dominion of Facts": Sarah Josepha Hale's Instructive Legacy.

ERIC Educational Resources Information Center

Henning, Martha L.

The 18th and 19th centuries saw a real tension between inductive and deductive methods of reason. Spokesperson for her era through her association with the popular "Godey's Ladies' Book," Sarah Josepha Hale addressed this tension in 1858, citing an article by Thomas Henry Buckle ascribing the method of deduction to women and that of induction to…

The Moral Dignity of Inductive Method and the Reconciliation of Science and Faith in Adam Sedgwick's "Discourse"

ERIC Educational Resources Information Center

Bellon, Richard

2012-01-01

Science's inductive method required patient, humble and self-controlled behavior; Christian revelation demanded the same virtues. The discoveries of science and the truths of scripture would always harmonize as long as both men of science and men of faith conducted themselves in scrupulous accordance with their duty. So ran a central argument in…

Energy Efficiency of Induction Motors Running Off Frequency Converters with Pulse-Width Voltage Modulation{sup 1}

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

Shvetsov, N. K., E-mail: elmash@em.ispu.ru

2016-11-15

The results of calculations of the increase in losses in an induction motor with frequency control and different forms of the supply voltage are presented. The calculations were performed by an analytic method based on harmonic analysis of the supply voltage as well as numerical calculation of the electromagnetic processes by the finite-element method.

System and method of adjusting the equilibrium temperature of an inductively-heated susceptor

DOEpatents

Matsen, Marc R; Negley, Mark A; Geren, William Preston

2015-02-24

A system for inductively heating a workpiece may include an induction coil, at least one susceptor face sheet, and a current controller coupled. The induction coil may be configured to conduct an alternating current and generate a magnetic field in response to the alternating current. The susceptor face sheet may be configured to have a workpiece positioned therewith. The susceptor face sheet may be formed of a ferromagnetic alloy having a Curie temperature and being inductively heatable to an equilibrium temperature approaching the Curie temperature in response to the magnetic field. The current controller may be coupled to the induction coil and may be configured to adjust the alternating current in a manner causing a change in at least one heating parameter of the susceptor face sheet.

The impact of different stator and rotor slot number combinations on iron losses of a three-phase induction motor at no-load

NASA Astrophysics Data System (ADS)

Marčič, T.; Štumberger, B.; Štumberger, G.; Hadžiselimović, M.; Zagradišnik, I.

The electromechanical characteristics of induction motors depend on the used stator and rotor slot combination. The correlation between the usage of different stator and rotor slot number combinations, magnetic flux density distributions, no-load iron losses and rated load winding over-temperatures for a specific induction motor is presented. The motor's magnetic field was analyzed by traces of the magnetic flux density vector, obtained by FEM. Post-processing of FE magnetic field solution was used for posterior iron loss calculation of the motor iron loss at no-load. The examined motor stator lamination had 36 semi-closed slots and the rotor laminations had 28, 33, 34, 44 and 46 semi-closed slots.

Effects of core/shell structure on magnetic induction heating promotion in Fe3O4/γ-Fe2O3 magnetic nanoparticles for hyperthermia

NASA Astrophysics Data System (ADS)

Lee, Shih-Chi; Fu, Chao-Ming; Chang, Fu-Hsiung

2013-10-01

Fe3O4/γ-Fe2O3 core-shell magnetic nanoparticles have demonstrated superior heating efficiency by applying the alternating magnetic field. The magnetic induction heating properties of core-shell magnetic nanoparticles were analyzed by the rate-dependent hysteresis model, taken into account the magnetic anisotropies and actual size distribution of particles. The analyzed results have disclosed the significance of magnetic anisotropies and shell-thickness to the promotion of magnetic induction heating performance. Further experiments about the cancer cells with uptake of these core-shell magnetic nanoparticles conjugated biocompatible cationic liposomes have achieved in vitro intracellular magnetically induced hyperthermia under a weak alternating magnetic field.

[The assessment of surgical treatment of patients with malignant pleural effusion].

PubMed

Lazarev, S M; Reshetov, A V; Kakysheva, O E; Nikolaev, G V; Kirillov, Iu V; Volgin, G N

2013-01-01

An analysis of results of 498 patients with malignant pleural effusion was made. All patients were divided into three groups depending on methods of treatment: in the first group of patients the puncture of pleural cavity and the evacuation of liquid were made against the background of complex treatment; in the second group of patients the thoracocentesis and suspension induction were performed; in the third group the video thoracoscopy was carried out. In an assessment of each method of treatment, the researchers came to the conclusion that in case when the patient had the sufficient functional capabilities, the doctors should give preference to the thoracoscopy operations and in case of severe somatic status the doctors should give preference to the drainage of pleural cavity with release from exudates and with subsequent introduction of talc as the most effective sclerosing agent.

Thin-Film Magnetic-Field-Response Fluid-Level Sensor for Non-Viscous Fluids

NASA Technical Reports Server (NTRS)

Woodard, Stanley E.; Shams, Qamar A.; Fox, Robert L.; Taylor, Bryant D.

2008-01-01

An innovative method has been developed for acquiring fluid-level measurements. This method eliminates the need for the fluid-level sensor to have a physical connection to a power source or to data acquisition equipment. The complete system consists of a lightweight, thin-film magnetic-field-response fluid-level sensor (see Figure 1) and a magnetic field response recorder that was described in Magnetic-Field-Response Measurement-Acquisition System (LAR-16908-1), NASA Tech Briefs, Vol. 30, No. 6 (June 2006), page 28. The sensor circuit is a capacitor connected to an inductor. The response recorder powers the sensor using a series of oscillating magnetic fields. Once electrically active, the sensor responds with its own harmonic magnetic field. The sensor will oscillate at its resonant electrical frequency, which is dependent upon the capacitance and inductance values of the circuit.

Human Primary Keratinocytes as a Tool for the Analysis of Caspase-1-Dependent Unconventional Protein Secretion.

PubMed

Strittmatter, Gerhard E; Garstkiewicz, Martha; Sand, Jennifer; Grossi, Serena; Beer, Hans-Dietmar

2016-01-01

Inflammasomes comprise a group of protein complexes, which activate the protease caspase-1 upon sensing a variety of stress factors. Active caspase-1 in turn cleaves and thereby activates the pro-inflammatory cytokines prointerleukin (IL)-1β and -18, and induces unconventional protein secretion (UPS) of mature IL-1β, IL-18, as well as of many other proteins involved in and required for induction of inflammation. Human primary keratinocytes (HPKs) represent epithelial cells able to activate caspase-1 in an inflammasome-dependent manner upon irradiation with a physiological dose of ultraviolet B (UVB) light. Here, we describe the isolation of keratinocytes from human skin, their cultivation, and induction of caspase-1-dependent UPS upon UVB irradiation as well as its siRNA- and chemical-mediated inhibition. In contrast to inflammasome activation of professional immune cells, UVB-irradiated HPKs represent a robust and physiological cell culture system for the analysis of UPS induced by active caspase-1.

Checkpoint-dependent RNR induction promotes fork restart after replicative stress.

PubMed

Morafraile, Esther C; Diffley, John F X; Tercero, José Antonio; Segurado, Mónica

2015-01-20

The checkpoint kinase Rad53 is crucial to regulate DNA replication in the presence of replicative stress. Under conditions that interfere with the progression of replication forks, Rad53 prevents Exo1-dependent fork degradation. However, although EXO1 deletion avoids fork degradation in rad53 mutants, it does not suppress their sensitivity to the ribonucleotide reductase (RNR) inhibitor hydroxyurea (HU). In this case, the inability to restart stalled forks is likely to account for the lethality of rad53 mutant cells after replication blocks. Here we show that Rad53 regulates replication restart through the checkpoint-dependent transcriptional response, and more specifically, through RNR induction. Thus, in addition to preventing fork degradation, Rad53 prevents cell death in the presence of HU by regulating RNR-expression and localization. When RNR is induced in the absence of Exo1 and RNR negative regulators, cell viability of rad53 mutants treated with HU is increased and the ability of replication forks to restart after replicative stress is restored.

The interplay between neuronal activity and actin dynamics mimic the setting of an LTD synaptic tag

PubMed Central

Szabó, Eszter C.; Manguinhas, Rita; Fonseca, Rosalina

2016-01-01

Persistent forms of plasticity, such as long-term depression (LTD), are dependent on the interplay between activity-dependent synaptic tags and the capture of plasticity-related proteins. We propose that the synaptic tag represents a structural alteration that turns synapses permissive to change. We found that modulation of actin dynamics has different roles in the induction and maintenance of LTD. Inhibition of either actin depolymerisation or polymerization blocks LTD induction whereas only the inhibition of actin depolymerisation blocks LTD maintenance. Interestingly, we found that actin depolymerisation and CaMKII activation are involved in LTD synaptic-tagging and capture. Moreover, inhibition of actin polymerisation mimics the setting of a synaptic tag, in an activity-dependent manner, allowing the expression of LTD in non-stimulated synapses. Suspending synaptic activation also restricts the time window of synaptic capture, which can be restored by inhibiting actin polymerization. Our results support our hypothesis that modulation of the actin cytoskeleton provides an input-specific signal for synaptic protein capture. PMID:27650071

Monitoring protein turnover during phosphate starvation-dependent autophagic degradation using a photoconvertible fluorescent protein aggregate in tobacco BY-2 cells

PubMed Central

Tasaki, Maiko; Asatsuma, Satoru; Matsuoka, Ken

2014-01-01

We have developed a system for quantitative monitoring of autophagic degradation in transformed tobacco BY-2 cells using an aggregate-prone protein comprised of cytochrome b5 (Cyt b5) and a tetrameric red fluorescent protein (RFP). Unfortunately, this system is of limited use for monitoring the kinetics of autophagic degradation because the proteins synthesized before and after induction of autophagy cannot be distinguished. To overcome this problem, we developed a system using kikume green-red (KikGR), a photoconvertible and tetrameric fluorescent protein that changes its fluorescence from green to red upon irradiation with purple light. Using the fusion protein of Cyt b5 and KikGR together with a method for the bulk conversion of KikGR, which we had previously used to convert the Golgi-localized monomeric KikGR fusion protein, we were able to monitor both the growth and de novo formation of aggregates. Using this system, we found that tobacco cells do not cease protein synthesis under conditions of phosphate (Pi)-starvation. Induction of autophagy under Pi-starvation, but not under sugar- or nitrogen-starvation, was specifically inhibited by phosphite, which is an analog of Pi with a different oxidation number. Therefore, the mechanism by which BY-2 cells can sense Pi-starvation and induce autophagy does not involve sensing a general decrease in energy supply and a specific Pi sensor might be involved in the induction of autophagy under Pi-starvation. PMID:24817874

Monitoring protein turnover during phosphate starvation-dependent autophagic degradation using a photoconvertible fluorescent protein aggregate in tobacco BY-2 cells.

PubMed

Tasaki, Maiko; Asatsuma, Satoru; Matsuoka, Ken

2014-01-01

We have developed a system for quantitative monitoring of autophagic degradation in transformed tobacco BY-2 cells using an aggregate-prone protein comprised of cytochrome b5 (Cyt b5) and a tetrameric red fluorescent protein (RFP). Unfortunately, this system is of limited use for monitoring the kinetics of autophagic degradation because the proteins synthesized before and after induction of autophagy cannot be distinguished. To overcome this problem, we developed a system using kikume green-red (KikGR), a photoconvertible and tetrameric fluorescent protein that changes its fluorescence from green to red upon irradiation with purple light. Using the fusion protein of Cyt b5 and KikGR together with a method for the bulk conversion of KikGR, which we had previously used to convert the Golgi-localized monomeric KikGR fusion protein, we were able to monitor both the growth and de novo formation of aggregates. Using this system, we found that tobacco cells do not cease protein synthesis under conditions of phosphate (Pi)-starvation. Induction of autophagy under Pi-starvation, but not under sugar- or nitrogen-starvation, was specifically inhibited by phosphite, which is an analog of Pi with a different oxidation number. Therefore, the mechanism by which BY-2 cells can sense Pi-starvation and induce autophagy does not involve sensing a general decrease in energy supply and a specific Pi sensor might be involved in the induction of autophagy under Pi-starvation.

Enzyme induction in neonates after fetal exposure to antiepileptic drugs

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

Rating, D.; Jaeger-Roman, E.; Nau, H.

1983-01-01

The /sup 13/C-AP breath test is shown to be a convenient, noninvasive method to monitor velocity and capacity of P450-dependent AP N-demethylation in infancy and childhood. According to /sup 13/C-AP breath tests, neonates have a very low capacity to eliminate /sup 13/CO/sub 2/, which is only 15 to 21% of the activity in adults. During the first year of life AP N-demethylation increases to reach its maximum at about 2 years; afterwards a slight decrease occurs. In 25 neonates exposed prenatally to different antiepileptic drugs /sup 13/C-AP breath test was efficiently used to prove that cytochrome AP N-demethylation was considerablymore » stimulated. After primidone/phenobarbitone, especially in combination with phenytoin, /sup 13/C elimination reaches and even surpasses the range for older children. Valproate exposure during fetal life is not consistently followed by a significant increase in AP N-demethylation. The enzyme induction demonstrated by /sup 13/C-AP breath test was often accompanied by accelerated metabolic clearance and shortened half-life times of transplacentally acquired antiepileptic drugs. There was good agreement between /sup 13/C-AP breath tests and pharmacokinetic data for primidone/phenobarbitone but not for phenytoin. In contrast, in the case of phenytoin exposure during pregnancy the pharmacokinetic parameters and the /sup 13/C breath test data will transport very different informations about enzyme induction in these neonates.« less

Induction of heme oxygenase-1 by chamomile protects murine macrophages against oxidative stress

PubMed Central

Bhaskaran, Natarajan; Shukla, Sanjeev; Kanwal, Rajnee; Srivastava, Janmejai K; Gupta, Sanjay

2012-01-01

Aims Protection of cells from oxidative insult may be possible through direct scavenging of reactive oxygen species, or through stimulation of intracellular antioxidant defense mechanisms by induction of antioxidant gene expression. In this study we investigated the cytoprotective effect of chamomile and elucidated the underlying mechanisms. Main Methods The cytoprotective effect of chamomile was examined on H2O2-induced cellular stress in RAW 264.7 murine macrophages. Key Findings RAW 264.7 murine macrophages treated with chamomile were protected from cell death caused by H2O2. Treatment with 50 μM H2O2 for 6 h caused significant increase in cellular stress accompanied by cell death in RAW 264.7 macrophages. Pretreatment with chamomile at 10-20 μg/mL for 16 h followed by H2O2 treatment protected the macrophages against cell death. Chamomile exposure significantly increased the expression of antioxidant enzymes viz. heme oxygenase-1 (HO-1), peroxiredoxin-1 (Prx-1), and thioredoxin-1 (Trx-1) in a dose-dependent manner, compared with their respective controls. Chamomile increased nuclear translocation of Nrf2 with increased phosphorylated Nrf2 levels, and binding to the antioxidant response element in the nucleus. Significance These molecular findings for the first time provide insights into the mechanisms underlying the induction of phase 2 enzymes through the Keap1-Nrf2 signaling pathway by chamomile, and provide evidence that chamomile possesses antioxidant and cytoprotective properties. PMID:22683429

Factors promoting in vitro excystation of Giardia muris cysts.

PubMed

Schaefer, F W; Rice, E W; Hoff, J C

1984-01-01

Giardia muris cysts, isolated from mouse faeces, excysted routinely at levels greater than 90%, when induced in 1X Hanks' supplemented with 17 mM glutathione, 29 mM L-cysteine-HCl, and 50 mM NaHCO3 for 30 minutes at 35 degrees C, followed by washing and suspension in trypsin-Tyrode's solution at pH 8.0. Although trypsin was not required in this final step, it enhanced the escape of the trophozoites from their cysts. G. muris excystation was dependent upon the length of the induction period, pH, oxidation-reduction potential and temperature. Optimal induction conditions for excystation were: an induction period of 5 to 30 min; pH of 2; 120 mV oxidation-reduction potential; and a temperature around 35 degrees C. A gradual decline in excystation occurred as pH and oxidation-reduction potential were changed to 7 and 57 mV, respectively. There was a pronounced increase in excystation percentages with increasing temperatures between 0 and 37 degrees C. At 40 degrees C and above, the G. muris cysts showed signs of inactivation. The thermal death point of G. muris cysts was determined to be about 54 degrees C. G. muris cysts showed no polarity; however, the tail or posterior trophozoite portion always emerged through one end of the cyst first. Cytokinensis began within the first hour after excystation. This method always produced extremely active, normal-looking G. muris trophozoites.

Mechanism of reentry induction by a 9-V battery in rabbit ventricles

PubMed Central

Burton, Rebecca A. B.; Kalla, Manish; Nanthakumar, Kumaraswamy; Plank, Gernot; Bub, Gil; Vigmond, Edward J.

2014-01-01

Although the application of a 9-V battery to the epicardial surface is a simple method of ventricular fibrillation induction, the fundamental mechanisms underlying this process remain unstudied. We used a combined experimental and modelling approach to understand how the interaction of direct current (DC) from a battery may induce reentrant activity within rabbit ventricles and its dependence on battery application timing and duration. A rabbit ventricular computational model was used to simulate 9-V battery stimulation for different durations at varying onset times during sinus rhythm. Corresponding high-resolution optical mapping measurements were conducted on rabbit hearts with DC stimuli applied via a relay system. DC application to diastolic tissue induced anodal and cathodal make excitations in both simulations and experiments. Subsequently, similar static epicardial virtual electrode patterns were formed that interacted with sinus beats but did not induce reentry. Upon battery release during diastole, break excitations caused single ectopics, similar to application, before sinus rhythm resumed. Reentry induction was possible for short battery applications when break excitations were slowed and forced to take convoluted pathways upon interaction with refractory tissue from prior make excitations or sinus beats. Short-lived reentrant activity could be induced for battery release shortly after a sinus beat for longer battery applications. In conclusion, the application of a 9-V battery to the epicardial surface induces reentry through a complex interaction of break excitations after battery release with prior induced make excitations or sinus beats. PMID:24464758

Mechanism of reentry induction by a 9-V battery in rabbit ventricles.

PubMed

Bishop, Martin J; Burton, Rebecca A B; Kalla, Manish; Nanthakumar, Kumaraswamy; Plank, Gernot; Bub, Gil; Vigmond, Edward J

2014-04-01

Although the application of a 9-V battery to the epicardial surface is a simple method of ventricular fibrillation induction, the fundamental mechanisms underlying this process remain unstudied. We used a combined experimental and modelling approach to understand how the interaction of direct current (DC) from a battery may induce reentrant activity within rabbit ventricles and its dependence on battery application timing and duration. A rabbit ventricular computational model was used to simulate 9-V battery stimulation for different durations at varying onset times during sinus rhythm. Corresponding high-resolution optical mapping measurements were conducted on rabbit hearts with DC stimuli applied via a relay system. DC application to diastolic tissue induced anodal and cathodal make excitations in both simulations and experiments. Subsequently, similar static epicardial virtual electrode patterns were formed that interacted with sinus beats but did not induce reentry. Upon battery release during diastole, break excitations caused single ectopics, similar to application, before sinus rhythm resumed. Reentry induction was possible for short battery applications when break excitations were slowed and forced to take convoluted pathways upon interaction with refractory tissue from prior make excitations or sinus beats. Short-lived reentrant activity could be induced for battery release shortly after a sinus beat for longer battery applications. In conclusion, the application of a 9-V battery to the epicardial surface induces reentry through a complex interaction of break excitations after battery release with prior induced make excitations or sinus beats.

Quantitative bioanalysis of strontium in human serum by inductively coupled plasma-mass spectrometry

PubMed Central

Somarouthu, Srikanth; Ohh, Jayoung; Shaked, Jonathan; Cunico, Robert L; Yakatan, Gerald; Corritori, Suzana; Tami, Joe; Foehr, Erik D

2015-01-01

Aim: A bioanalytical method using inductively-coupled plasma-mass spectrometry to measure endogenous levels of strontium in human serum was developed and validated. Results & methodology: This article details the experimental procedures used for the method development and validation thus demonstrating the application of the inductively-coupled plasma-mass spectrometry method for quantification of strontium in human serum samples. The assay was validated for specificity, linearity, accuracy, precision, recovery and stability. Significant endogenous levels of strontium are present in human serum samples ranging from 19 to 96 ng/ml with a mean of 34.6 ± 15.2 ng/ml (SD). Discussion & conclusion: Calibration procedures and sample pretreatment were simplified for high throughput analysis. The validation demonstrates that the method was sensitive, selective for quantification of strontium (88Sr) and is suitable for routine clinical testing of strontium in human serum samples. PMID:28031925

Identification of Malicious Web Pages by Inductive Learning

NASA Astrophysics Data System (ADS)

Liu, Peishun; Wang, Xuefang

Malicious web pages are an increasing threat to current computer systems in recent years. Traditional anti-virus techniques focus typically on detection of the static signatures of Malware and are ineffective against these new threats because they cannot deal with zero-day attacks. In this paper, a novel classification method for detecting malicious web pages is presented. This method is generalization and specialization of attack pattern based on inductive learning, which can be used for updating and expanding knowledge database. The attack pattern is established from an example and generalized by inductive learning, which can be used to detect unknown attacks whose behavior is similar to the example.

Exploring inductive linearization for pharmacokinetic-pharmacodynamic systems of nonlinear ordinary differential equations.

PubMed

Hasegawa, Chihiro; Duffull, Stephen B

2018-02-01

Pharmacokinetic-pharmacodynamic systems are often expressed with nonlinear ordinary differential equations (ODEs). While there are numerous methods to solve such ODEs these methods generally rely on time-stepping solutions (e.g. Runge-Kutta) which need to be matched to the characteristics of the problem at hand. The primary aim of this study was to explore the performance of an inductive approximation which iteratively converts nonlinear ODEs to linear time-varying systems which can then be solved algebraically or numerically. The inductive approximation is applied to three examples, a simple nonlinear pharmacokinetic model with Michaelis-Menten elimination (E1), an integrated glucose-insulin model and an HIV viral load model with recursive feedback systems (E2 and E3, respectively). The secondary aim of this study was to explore the potential advantages of analytically solving linearized ODEs with two examples, again E3 with stiff differential equations and a turnover model of luteinizing hormone with a surge function (E4). The inductive linearization coupled with a matrix exponential solution provided accurate predictions for all examples with comparable solution time to the matched time-stepping solutions for nonlinear ODEs. The time-stepping solutions however did not perform well for E4, particularly when the surge was approximated by a square wave. In circumstances when either a linear ODE is particularly desirable or the uncertainty in matching the integrator to the ODE system is of potential risk, then the inductive approximation method coupled with an analytical integration method would be an appropriate alternative.

Nonylphenol-mediated CYP induction is PXR-dependent: The use of humanized mice and human hepatocytes suggests that hPXR is less sensitive than mouse PXR to nonylphenol treatment

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

Mota, Linda C.; Barfield, Christina; Hernandez, Juan P.

2011-05-01

Nonylphenol (NP), a by-product of alkylphenol ethoxylates, is a pervasive surfactant that activates the xenosensing nuclear receptor, the pregnane X-receptor (PXR) in transactivation assays in vitro. We are interested in determining if NP activates PXR in vivo, determining if hPXR and mPXR act similarly, and investigating the role of PXR in protecting individuals from NP. Wild-type (WT), PXR-null, and humanized PXR (hPXR) mice were treated with NP at 0, 50 or 75 mg/kg/day for one week, and cytochrome P450 (CYP) induction, liver histopathology, and serum NP concentrations were examined. WT mice treated with NP showed induction of Cyp2b, and male-specificmore » induction of Cyp2c and Cyp3a. CYPs were not induced in PXR-null mice, demonstrating that PXR is necessary for NP-mediated CYP induction. CAR-mediated CYP induction was not observed in the PXR-null mice despite previous data demonstrating that NP is also a CAR activator. hPXR mice only showed moderate Cyp induction, suggesting that hPXR is not as sensitive to NP as mPXR in vivo. NP-mediated Cyp3a induction from three human hepatocyte donors was not significant, confirming that hPXR is not very sensitive to NP-mediated CYP induction. Lastly, mice with PXR (mPXR and hPXR) showed lower NP serum concentrations than PXR-null mice treated with NP suggesting that PXR plays a role in decreasing liver toxicity by basally regulating phase I-III detoxification enzymes that promote the metabolism and elimination of NP. In summary, PXR is required for NP-mediated CYP-induction, mPXR mediates greater CYP induction than hPXR in vivo, and the presence of PXR, especially mPXR, is associated with altered histopathology and increased clearance of NP.« less

Nonylphenol-mediated CYP induction is PXR-dependent: The use of humanized mice and human hepatocytes suggests that hPXR is less sensitive than mouse PXR to nonylphenol treatment

PubMed Central

Mota, Linda C; Barfield, Christina; Hernandez, Juan P; Baldwin, William S.

2011-01-01

Nonylphenol (NP), a by-product of alkylphenol ethoxylates, is a pervasive surfactant that activates the xenosensing nuclear receptor, the pregnane X-receptor (PXR) in transactivation assays in vitro. We are interested in determining if NP activates PXR in vivo, determining if hPXR and mPXR act similarly, and investigating the role of PXR in protecting individuals from NP. Wild-type (WT), PXR-null, and humanized PXR (hPXR) mice were treated with NP at 0, 50 or 75 mg/kg/day for one week, and cytochrome P450 (CYP) induction, liver histopathology, and serum NP concentrations were examined. WT mice treated with NP showed induction of Cyp2b, and male-specific induction of Cyp2c and Cyp3a. CYPs were not induced in PXR-null mice, demonstrating that PXR is necessary for NP-mediated CYP induction. CAR-mediated CYP induction was not observed in the PXR-null mice despite previous data demonstrating NP is also a CAR activator. hPXR mice only showed moderate Cyp induction, suggesting that hPXR is not as sensitive to NP as mPXR in vivo. NP-mediated Cyp3a induction from three human hepatocyte donors was not significant, confirming that hPXR is not very sensitive to NP-mediated CYP induction. Lastly, mice with PXR (mPXR and hPXR) showed lower NP serum concentrations than PXR-null mice treated with NP suggesting that PXR plays a role in decreasing liver toxicity by basally regulating Phase I-III detoxification enzymes that promote the metabolism and elimination of NP. In summary, PXR is required for NP-mediated CYP-induction, and mPXR mediates greater CYP induction than hPXR in vivo, and the presence of PXR, especially mPXR, is associated with altered histopathology and increased clearance of NP. PMID:21376070

CYCLIC AMP-DEPENDENT PROTEIN KINASE INDUCTION BY POLYCHLORINATED BIPHENYLS (PCBS) STIMULATES CREB PHOSPHORYLATION VIA A CALCIUM-DEPENDENT, PKC-INDEPENDENT PATHWAY IN CORTICAL NEURONS.

EPA Science Inventory

We have previously demonstrated that the PCB mixture, Aroclor 1254 (A1254), increases the phosphorylated form of CREB (pCREB), the cAMP-responsive element binding protein. This transcription factor is important in nervous system development and plasticity. Phosphorylation
of C...

Radiation induction of drug resistance in RIF-1: Correlation of tumor and cell culture results

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

Moulder, J.E.; Hopwood, L.E.; Volk, D.M.

1991-02-01

The RIF-1 tumor line contains cells that are resistant to various anti-neoplastic drugs, including 5-fluorouracil (5FU), methotrexate (MTX), adriamycin (ADR), and etoposide (VP16). The frequency of these drug-resistant cells is increased after irradiation. The frequency of drug-resistant cells and the magnitude of radiation-induced drug resistance are different in cell culture than in tumors. The dose-response and expression time relationships for radiation induction of drug resistance observed in RIF-1 tumors are unusual.We hypothesize that at high radiation doses in vivo, we are selecting for cells that are both drug resistant and radiation resistant due to microenvironmental factors, whereas at low radiationmore » doses in vivo and all radiation doses in vitro, we are observing true mutants. These studies indicate that there can be significant differences in drug-resistance frequencies between tumors and their cell lines of origin, and that radiation induction of drug resistance depends significantly on whether the induction is done in tumors or in cell culture. These results imply that theories about the induction of drug resistance that are based on cell culture studies may be inapplicable to the induction of drug resistance in tumors.« less

Efficiencies of induction of DNA double strand breaks in solution by photoabsorption at phosphorus and platinum.

PubMed

Maeda, Munetoshi; Kobayashi, Katsumi; Hieda, Kotaro

2004-01-01

This paper aims at determining and comparing the cross sections and quantum yields for DNA strand break induction by the Auger effect at the K-shell of phosphorus and at the LIII-shell of platinum. Using synchrotron radiation, free and Pt-bound pBR322 plasmid DNA were irradiated in solution with monochromatic X-rays, the energies of which were 2.153 and 2.147 keV, corresponding to "on" and "below" the phosphorus K-shell photoabsorption, and 11.566 and 11.542 keV for "above" and "below" the L(III)-shell photoabsorption of platinum, respectively. To suppress indirect effects by hydroxyl radicals, DMSO (1M) was used as a scavenger. The inner-shell photoabsorption of phosphorus and of platinum significantly increased the induction of DNA double strand breaks (DSB), whereas it had little effect on single strand break (SSB) induction. The quantum yields for the induction of DSB were calculated to be 0.017 and 1.13, in the case of phosphorus and platinum, respectively. CONCLSIONS: The value of the quantum yield for the DSB induction of platinum was about 66-fold larger than that for the phosphorus. These results clearly demonstrate that the quantum yield of DSB depends upon the magnitude of the Auger cascade.

Betulinic acid inhibits colon cancer cell and tumor growth and induces proteasome-dependent and -independent downregulation of specificity proteins (Sp) transcription factors

PubMed Central

2011-01-01

Background Betulinic acid (BA) inhibits growth of several cancer cell lines and tumors and the effects of BA have been attributed to its mitochondriotoxicity and inhibition of multiple pro-oncogenic factors. Previous studies show that BA induces proteasome-dependent degradation of specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 in prostate cancer cells and this study focused on the mechanism of action of BA in colon cancer cells. Methods The effects of BA on colon cancer cell proliferation and apoptosis and tumor growth in vivo were determined using standardized assays. The effects of BA on Sp proteins and Sp-regulated gene products were analyzed by western blots, and real time PCR was used to determine microRNA-27a (miR-27a) and ZBTB10 mRNA expression. Results BA inhibited growth and induced apoptosis in RKO and SW480 colon cancer cells and inhibited tumor growth in athymic nude mice bearing RKO cells as xenograft. BA also decreased expression of Sp1, Sp3 and Sp4 transcription factors which are overexpressed in colon cancer cells and decreased levels of several Sp-regulated genes including survivin, vascular endothelial growth factor, p65 sub-unit of NFκB, epidermal growth factor receptor, cyclin D1, and pituitary tumor transforming gene-1. The mechanism of action of BA was dependent on cell context, since BA induced proteasome-dependent and proteasome-independent downregulation of Sp1, Sp3 and Sp4 in SW480 and RKO cells, respectively. In RKO cells, the mechanism of BA-induced repression of Sp1, Sp3 and Sp4 was due to induction of reactive oxygen species (ROS), ROS-mediated repression of microRNA-27a, and induction of the Sp repressor gene ZBTB10. Conclusions These results suggest that the anticancer activity of BA in colon cancer cells is due, in part, to downregulation of Sp1, Sp3 and Sp4 transcription factors; however, the mechanism of this response is cell context-dependent. PMID:21864401

Aerosol detection efficiency in inductively coupled plasma mass spectrometry

NASA Astrophysics Data System (ADS)

Hubbard, Joshua A.; Zigmond, Joseph A.

2016-05-01

An electrostatic size classification technique was used to segregate particles of known composition prior to being injected into an inductively coupled plasma mass spectrometer (ICP-MS). Size-segregated particles were counted with a condensation nuclei counter as well as sampled with an ICP-MS. By injecting particles of known size, composition, and aerosol concentration into the ICP-MS, efficiencies of the order of magnitude aerosol detection were calculated, and the particle size dependencies for volatile and refractory species were quantified. Similar to laser ablation ICP-MS, aerosol detection efficiency was defined as the rate at which atoms were detected in the ICP-MS normalized by the rate at which atoms were injected in the form of particles. This method adds valuable insight into the development of technologies like laser ablation ICP-MS where aerosol particles (of relatively unknown size and gas concentration) are generated during ablation and then transported into the plasma of an ICP-MS. In this study, we characterized aerosol detection efficiencies of volatile species gold and silver along with refractory species aluminum oxide, cerium oxide, and yttrium oxide. Aerosols were generated with electrical mobility diameters ranging from 100 to 1000 nm. In general, it was observed that refractory species had lower aerosol detection efficiencies than volatile species, and there were strong dependencies on particle size and plasma torch residence time. Volatile species showed a distinct transition point at which aerosol detection efficiency began decreasing with increasing particle size. This critical diameter indicated the largest particle size for which complete particle detection should be expected and agreed with theories published in other works. Aerosol detection efficiencies also displayed power law dependencies on particle size. Aerosol detection efficiencies ranged from 10- 5 to 10- 11. Free molecular heat and mass transfer theory was applied, but evaporative phenomena were not sufficient to explain the dependence of aerosol detection on particle diameter. Additional work is needed to correlate experimental data with theory for metal-oxides where thermodynamic property data are sparse relative to pure elements. Lastly, when matrix effects and the diffusion of ions inside the plasma were considered, mass loading was concluded to have had an effect on the dependence of detection efficiency on particle diameter.

Icing-Protection Requirements for Reciprocating-Engine Induction System

NASA Technical Reports Server (NTRS)

Coles, Willard D; Rollin, Vern G; Mulholland, Donald R

1950-01-01

Despite the development of relatively ice-free fuel-metering systems, the widespread use of alternate and heated-air intakes, and the use of alcohol for emergency de-icing, icing of aircraft-engine induction systems is a serious problem. Investigations have been made to study and to combat all phases of this icing problem. From these investigations, criterions for safe operation and for design of new induction systems have been established. The results were obtained from laboratory investigations of carburetor-supercharger combinations, wind-tunnel investigations of air scoops, multicylinder-engine studies, and flight investigations. Characteristics of three forms of ice, impact, throttling, and fuel evaporation were studied. The effects of several factors on the icing characteristics were also studied and included: (1) atmospheric conditions, (2) engine and air-scoop configurations, including light-airplane system, (3) type fuel used, and (4) operating variables, such as power condition, use of a manifold pressure regulator, mixture setting, carburetor heat, and water-alcohol injection. In addition, ice-detection methods were investigated and methods of preventing and removing induction-system ice were studied. Recommendations are given for design and operation with regard to induction-system design.

Ahr2-dependance of PCB126 effects on the swimbladder in relation to expression of CYP1 and cox-2 genes in developing zebrafish

PubMed Central

Jönsson, Maria E.; Kubota, Akira; Timme-Laragy, Alicia; Woodin, Bruce; Stegeman, John J.

2012-01-01

The teleost swimbladder is assumed a homolog of the tetrapod lung. Both swimbladder and lung are developmental targets of persistent aryl hydrocarbon receptor (AHR1) agonists; in zebrafish (Danio rerio) the swimbladder fails to inflate with exposure to 3,3’,4,4’,5-pentachlorobiphenyl (PCB126). The mechanism for this effect is unknown, but studies have suggested roles of cytochrome P4501 (CYP1) and cyclooxygenase 2 (Cox-2) in some Ahr-mediated developmental effects in zebrafish. We determined relationships between swimbladder inflation and CYP1 and Cox-2 mRNA expression in PCB126-exposed zebrafish embryos. We also examined effects on β-catenin dependent transcription, histological effects, and Ahr2 dependance of the effect of PCB126 on swimbladder using morpholinos targeting ahr2. One-day-old embryos were exposed to waterborne PCB126 or carrier (DMSO) for 24 h and then held in clean water until day 4, a normal time for swimbladder inflation. The effects of PCB126 were concentration-dependent with EC50 values of 1.4 to 2.0 nM for induction of the CYP1s, 3.7 and 5.1 nM (or higher) for cox-2a and cox-2b induction, and 2.5 nM for inhibition of swimbladder inflation. Histological defects included a compaction of the developing bladder. Ahr2-morpholino treatment rescued the effect of PCB126 (5 nM) on swimbladder inflation and blocked induction of CYP1A, cox-2a, and cox-2b. With 2 nM PCB126 approximately 30% of eleutheroembryos2 failed to inflate the swimbladder, but there was no difference in CYP1 or cox-2 mRNA expression between those embryos and embryos showing inflated swimbladder. Our results indicate that PCB126 blocks swimbladder inflation via an Ahr2-mediated mechanism. This mechanism seems independent of CYP1 or cox-2 mRNA induction but may involve abnormal development of swimbladder cells. PMID:23036320

Effectiveness, safety and feasibility of extended-release naltrexone for opioid dependence: a 9-month follow-up to a 3-month randomized trial.

PubMed

Solli, Kristin Klemmetsby; Latif, Zill-E-Huma; Opheim, Arild; Krajci, Peter; Sharma-Haase, Kamni; Benth, Jūratė Šaltytė; Tanum, Lars; Kunoe, Nikolaj

2018-05-28

This is a follow-up study of a previously published randomized clinical trial conducted in Norway that compared extended-release naltrexone (XR-NTX) to buprenorphine-naloxone (BP-NLX) over 3 months. At the conclusion of the trial, participants were offered their choice of study medication for an additional 9 months. While BP-NLX was available at no cost through opioid maintenance treatment programmes, XR-NTX was available only through study participation, accounting for why almost all participants chose XR-NTX in the follow-up. The aim of this follow-up study was to compare differences in outcome between adults with opioid dependence continuing XR-NTX and those inducted on XR-NTX for a 9-month period, on measures of effectiveness, safety and feasibility. In this prospective cohort study, participants were either continuing XR-NTX, changed from BP-NLX to XR-NTX or re-included into the study and inducted on XR-NTX treatment. Five urban, out-patient addiction clinics in Norway. Opioid-dependent adults continuing (n = 54) or inducted on (n = 63) XR-NTX. XR-NTX administrated as intramuscular injections (380 mg) every fourth week. Data on retention, use of heroin and other illicit substances, opioid craving, treatment satisfaction, addiction-related problems and adverse events were reported every fourth week. Nine-month follow-up completion rates were 51.9% among participants continuing XR-NTX in the follow-up and 47.6% among those inducted on XR-NTX. Opioid abstinence rates were, respectively, 53.7 and 44.4%. No significant group differences were found in use of heroin and other opioids. Opioid-dependent individuals who elect to switch from buprenorphine-naltrexone treatment after 3 months to extended-release naltrexone treatment for 9 months appear to experience similar treatment completion and abstinence rates and similar adverse event profiles to individuals who had been on extended-release naltrexone from the start of treatment. © 2018 Society for the Study of Addiction.

Solenoid-free plasma startup in NSTX using transient CHI

NASA Astrophysics Data System (ADS)

Raman, R.; Jarboe, T. R.; Mueller, D.; Nelson, B. A.; Bell, M. G.; Bell, R.; Gates, D.; Gerhardt, S.; Hosea, J.; Kaita, R.; Kugel, H.; LeBlanc, B.; Maingi, R.; Maqueda, R.; Menard, J.; Nagata, M.; Ono, M.; Paul, S.; Roquemore, L.; Sabbagh, S.; Soukhanovskii, V.; Taylor, G.

2009-06-01

Experiments in NSTX have now demonstrated the coupling of toroidal plasmas produced by the technique of coaxial helicity injection (CHI) to inductive sustainment and ramp-up of the toroidal plasma current. In these discharges, the central Ohmic transformer was used to apply an inductive loop voltage to discharges with a toroidal current of about 100 kA created by CHI. The coupled discharges have ramped up to >700 kA and transitioned into an H-mode demonstrating compatibility of this startup method with conventional operation. The electron temperature in the coupled discharges reached over 800 eV and the resulting plasma had low inductance, which is preferred for long-pulse high-performance discharges. These results from NSTX in combination with the previously obtained record 160 kA non-inductively generated startup currents in an ST or tokamak in NSTX demonstrate that CHI is a viable solenoid-free plasma startup method for future STs and tokamaks.

Methods of Analysis by the U.S. Geological Survey National Water Quality Laboratory - Determination of Elements in Whole-Water Digests Using Inductively Coupled Plasma-Optical Emission Spectrometry and Inductively Coupled Plasma-Mass Spectrometry

USGS Publications Warehouse

Garbarino, John R.; Struzeski, Tedmund M.

1998-01-01

Inductively coupled plasma-optical emission spectrometry (ICP-OES) and inductively coupled plasma-mass spectrometry (ICP-MS) can be used to determine 26 elements in whole-water digests. Both methods have distinct advantages and disadvantages--ICP-OES is capable of analyzing samples with higher elemental concentrations without dilution, however, ICP-MS is more sensitive and capable of determining much lower elemental concentrations. Both techniques gave accurate results for spike recoveries, digested standard reference-water samples, and whole-water digests. Average spike recoveries in whole-water digests were 100 plus/minus 10 percent, although recoveries for digests with high dissolved-solid concentrations were lower for selected elements by ICP-MS. Results for standard reference-water samples were generally within 1 standard deviation of hte most probable values. Statistical analysis of the results from 43 whole-water digest indicated that there was no significant difference among ICP-OES, ICP-MS, and former official methods of analysis for 24 of the 26 elements evaluated.

[Evaluation of the efficacy and safety of Foley catheter pre-induction of labor].

PubMed

Jagielska, Iwona; Kazdepka-Ziemińska, Anita; Janicki, Radosław; Fórmaniak, Jacek; Walentowicz-Sadłecka, Małgorzata; Grabiec, Marek

2013-03-01

Labor induction is being increasingly used (15-30% of pregnancies). The most common indications include late pregnancy preeclampsia, intrauterine fetal growth retardation (IUGR), hypertension. Preinduction by speeding up the ripening of the cervix increases the chances of successful induction. There are mechanical and pharmacological methods of pre-induction: the Foley catheter hygroscopic dilators, prostaglandin gel, misoprostol. There are various schemes of labor pre-induction and the differences relate primarily to duration of catheter time, amniotomy or the start of the oxytocin. Numerous studies on pre-induction and induction of labor aimed to compare the efficacy of these different methods. The effectiveness of the Foley catheter is usually assessed by comparing cervical maturity (Bishop score) and ripening of the cervix, evaluated in centimeters, before and after removing the cathetec time to labor since pre-induction and the number of births. In order to select the appropriate method, its safety for the mother and the fetus/newborn needs to be assessed. According to most authors, the use of a Foley catheter does not cause over-stimulation of the uterus, does not increase the risk of rupture or intrauterine infection, and does not adversely affect the fetus and newborn. To assess the efficacy and safety of labor pre-induction using a Foley catheter The study included 109 women hospitalized between 03.01.2011 and 11.30.2011, who underwent labor pre-induction with a Foley catheter The inclusion criteria were: one fetal pregnancy longitudinal cephalic fetal position, completed 36 weeks of pregnancy fetal bladder preserved, Bishop score < 5 points. The exclusion criteria were: placenta previa, uterine infection, unexplained bleeding, abnormal fetal heart rate, and other reasons preventing vaginal delivery such as fetal weight above 4500 g. Vaginal swabs for the presence of Streptococcus agalactiae (GBS) were obtained from each patient. In case of a positive result perinatal antibiotic prophylaxis was administered before insertion of the catheter The study group was divided into two subgroups according to parity: primiparous and multiparous. Indications for induction, method of pregnancy termination, the pregnancy and its complications were evaluated. The condition of the newborns was evaluated using the Apgar score, cord blood pH and infant birth weight. We analyzed cervical ripeness (Bishop score) before the insertion and after the removal of the catheter and serum C-reactive protein (CRP) before and 20 hours after insertion. CRP was not studied in pregnant women diagnosed with GBS colonization. The results were compared between the subgroups. An increase in the Bishop score to> 5 and delivery within 12 hours since the planned removal of the catheter regardless of the method of pregnancy and the use of oxytocin, was considered as successful induction of labor Catheter pre-induction was performed in 109 pregnant women, what amounted to 7.87% all of deliveries in our department during the analyzed period. Mean patient age was 29.3 +/- 5.35 years, mean duration of pregnancy 40 weeks of gestation (+/- 1 week 5 days), and primiparas constituted 66.06% of all cases. The most common indication for labor induction was post-term pregnancy (55.05%), hypertension and preeclampsia (16.51%). The following complications were observed in the study group after insertion of the catheter: 8 (7.34%) cases of premature rupture of the membranes (PROM), but none of them occurred in the process of inserting the catheter 11 (10.09%) women had the catheter removed (patients request) due to pain and the feeling of discomfort before the scheduled time, 2 (1.84%) cases of bleeding (in the first case the cesarean section was performed and the baby was born in a good overall condition, in the second case the bleeding subsided spontaneously). There was a statistically significant increase in the Bishop score for the entire study group and in the two subgroups. Mean increase in the Bishop score was 2.68 +/- 1.39 points for the entire cohort (p < 0.005). The rate of successful pre-induction resulting in a delivery was 69.4%, with vaginal births accounting for 66.67% of all cases. Also, 30.66% of the pregnant women did not require the use of oxytocin. The most common indication for cesarean section was threatening intrauterine fetal asphyxia. Higher efficiency of pre-induction was found in the multiparous group. The observed increase in CRP (p < 0.005) was within the normal range for pregnant women (< 12 mg/I). None of the patients showed any clinical signs of infection. Mean birth weight of the infants was 3392 +/- 644.72 g, mean Apgar score was 9.5 +/- 0.80 and mean cord blood pH was 7.3 +/- 0.08. The Foley catheter is an effective method of inducing cervical maturation. The Foley catheter is safe method of labor induction for the mother fetus and newborn.

Ultra-fast boriding of metal surfaces for improved properties

DOEpatents

Timur, Servet; Kartal, Guldem; Eryilmaz, Osman L.; Erdemir, Ali

2015-02-10

A method of ultra-fast boriding of a metal surface. The method includes the step of providing a metal component, providing a molten electrolyte having boron components therein, providing an electrochemical boriding system including an induction furnace, operating the induction furnace to establish a high temperature for the molten electrolyte, and boriding the metal surface to achieve a boride layer on the metal surface.

Assessment of Remaining Lubricant Life

DTIC Science & Technology

1986-11-01

tioxidant, inexpensive spectrophotometers are used. However, the greatest advantage of the Mitsubishi chemical stressing technique was the fact that it uses...samples, the method’s main advantage over the thermal stressing techniques is eliminated. The colorimetric method had the advantage over induction period...decrease of 18 torr. The main advantage of defining the induction period in this manner is that it eliminates any need for interpretation by the

Razumikhin-Type Stability Criteria for Differential Equations with Delayed Impulses.

PubMed

Wang, Qing; Zhu, Quanxin

2013-01-01

This paper studies stability problems of general impulsive differential equations where time delays occur in both differential and difference equations. Based on the method of Lyapunov functions, Razumikhin technique and mathematical induction, several stability criteria are obtained for differential equations with delayed impulses. Our results show that some systems with delayed impulses may be exponentially stabilized by impulses even if the system matrices are unstable. Some less restrictive sufficient conditions are also given to keep the good stability property of systems subject to certain type of impulsive perturbations. Examples with numerical simulations are discussed to illustrate the theorems. Our results may be applied to complex problems where impulses depend on both current and past states.

Cost Assessment of Implementation of Immune Tolerance Induction in Iran.

PubMed

Cheraghali, Abdol Majid; Eshghi, Peyman

2012-05-01

A number of hemophilia A patients who receive clotting factors may develop antibodies (inhibitors) against clotting factors. The immune tolerance induction (ITI) method has proved to be a very cost-effective alternative to bypassing agents. Iran's national health authority is interested in implementing the ITI method for the management of hemophilia patients with inhibitors. The objective of this study was to calculate the breakeven point between costs attributed to the ITI method and the use of bypassing agents for the management of high-responder hemophilia patients with inhibitors. This study assessed costs attributed to the implementation of ITI for the management of Iranian hemophilia patients with costs of high-titer and high-responding inhibitors from the perspective of the national health system. The main objective was to find the breakeven point for the ITI method in comparison with the use of bypassing medicine, recombinant factor VIIa (Novoseven). Based on the sensitivity analysis performed, the breakeven point mainly depends on costs of factor VIII, Novoseven, and the success rate of the ITI intervention. According to this analysis, the breakeven point of ITI and Novoseven methods varies between 16 and 34 months posttreatment. The optimized point is about 17 months posttreatment. Iran's national health system spends more than 24 million euros for providing bypassing agents to about 124 hemophilia patients with inhibitors. Because of limited resources available in Iran's health sector, this is a huge burden. Results of this study show that the implementation of the ITI method for the management of Iranian hemophilia patients with inhibitors is a cost-saving method and Iran's health system will recover all the expenditure related to the implementation of ITI in less than 2 years and will make a considerable saving along with providing standard care for these patients. Copyright © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Serotonin is an endogenous regulator of intestinal CYP1A1 via AhR.

PubMed

Manzella, Christopher; Singhal, Megha; Alrefai, Waddah A; Saksena, Seema; Dudeja, Pradeep K; Gill, Ravinder K

2018-04-17

Aryl hydrocarbon receptor (AhR) is a nuclear receptor that controls xenobiotic detoxification via induction of cytochrome P450 1A1 (CYP1A1) and regulates immune responses in the intestine. Metabolites of L-tryptophan activate AhR, which confers protection against intestinal inflammation. We tested the hypothesis that serotonin (5-HT) is an endogenous activator of AhR in intestinal epithelial cells. Treatment of Caco-2 monolayers with 5-HT induced CYP1A1 mRNA in a time- and concentration-dependent manner and also stimulated CYP1A1 activity. CYP1A1 induction by 5-HT was dependent upon uptake via serotonin transporter (SERT). Antagonism of AhR and knockdown of AhR and its binding partner aryl hydrocarbon receptor nuclear translocator (ARNT) attenuated CYP1A1 induction by 5-HT. Activation of AhR was evident by its nuclear translocation after 5-HT treatment and by induction of an AhR-responsive luciferase reporter. In vivo studies showed a dramatic decrease in CYP1A1 expression and other AhR target genes in SERT KO ileal mucosa by microarray analysis. These results suggest that intracellular accumulation of 5-HT via SERT induces CYP1A1 expression via AhR in intestinal epithelial cells, and SERT deficiency in vivo impairs activation of AhR. Our studies provide a novel link between the serotonergic and AhR pathways which has implications in xenobiotic metabolism and intestinal inflammation.

Timing and Frequency of Sublethal Exposure Modifies the Induction and Retention of Increased Insecticide Tolerance in Wood Frogs (Lithobates sylvaticus).

PubMed

Jones, Devin K; Yates, Erika K; Mattes, Brian M; Hintz, William D; Schuler, Matthew S; Relyea, Rick A

2018-05-22

While the paradigm for increased tolerance to pesticides has been by selection on constitutive (naïve) traits, recent research has shown it can also occur through phenotypic plasticity. However, the time period in which induction can occur, the duration of induced tolerance, and the influence of multiple induction events remain unknown. We hypothesized that the induction of increased pesticide tolerance is limited to early sensitive periods, the magnitude of induced tolerance depends on the number of exposures, and the retention of induced tolerance depends on the time elapsed after an exposure and the number of exposures. To test these hypotheses, we exposed wood frog tadpoles to either a no-carbaryl control (water) or 0.5 mg/L carbaryl at four time periods, and later tested their tolerance to carbaryl using time-to-death assays. We discovered that tadpoles induced increased tolerance early and midway, but not late, in our experiment and their constitutive tolerance increased with age. We found no difference in the magnitude of induced tolerance following one or two exposures. Lastly, induced pesticide tolerance was reversed within 6 d, but was retained only when tadpoles experienced all four consecutive exposures. Phenotypic plasticity provides an immediate response for sensitive amphibian larvae to early pesticide exposures and reduces phenotypic mismatches in aquatic environments contaminated by agrochemicals. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Role of Glucagon-Like Peptide-1 and Gastric Inhibitory Peptide in Anorexia Induction Following Oral Exposure to the Trichothecene Mycotoxin Deoxynivalenol (Vomitoxin).

PubMed

Jia, Hui; Wu, Wen-Da; Lu, Xi; Zhang, Jie; He, Cheng-Hua; Zhang, Hai-Bin

2017-09-01

Deoxynivalenol (DON), which is a Type B trichothecene mycotoxin produced by Fusarium, frequently contaminates cereal staples, such as wheat, barley and corn. DON threatens animal and human health by suppressing food intake and impairing growth. While anorexia induction in mice exposed to DON has been linked to the elevation of the satiety hormones cholecystokinin and peptide YY3-36 in plasma, the effects of DON on the release of other satiety hormones, such as glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP), have not been established. The purpose of this study was to determine the roles of GLP-1 and GIP in DON-induced anorexia. In a nocturnal mouse food consumption model, the elevation of plasma GLP-1 and GIP concentrations markedly corresponded to anorexia induction by DON. Pretreatment with the GLP-1 receptor antagonist Exendin9-39 induced a dose-dependent attenuation of both GLP-1- and DON-induced anorexia. In contrast, the GIP receptor antagonist Pro3GIP induced a dose-dependent attenuation of both GIP- and DON-induced anorexia. Taken together, these results suggest that GLP-1 and GIP play instrumental roles in anorexia induction following oral exposure to DON, and the effect of GLP-1 is more potent and long-acting than that of GIP. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Indoleamine 2,3-dioxygenase-dependent tryptophan metabolites contribute to tolerance induction during allergen immunotherapy in a mouse model.

PubMed

Taher, Yousef A; Piavaux, Benoit J A; Gras, Reneé; van Esch, Betty C A M; Hofman, Gerard A; Bloksma, Nanne; Henricks, Paul A J; van Oosterhout, Antoon J M

2008-04-01

The tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO) has been implicated in immune suppression and tolerance induction. We examined (1) whether IDO activity is required during tolerance induction by allergen immunotherapy or for the subsequent suppressive effects on asthma manifestations and (2) whether tryptophan depletion or generation of its downstream metabolites is involved. Ovalbumin (OVA)-sensitized and OVA-challenged BALB/c mice that display increased airway responsiveness to methacholine, serum OVA-specific IgE levels, bronchoalveolar eosinophilia, and TH2 cytokine levels were used as a model of allergic asthma. Sensitized mice received subcutaneous optimal (1 mg) or suboptimal (100 microg) OVA immunotherapy. Inhibition of IDO by 1-methyl-DL-tryptophan during immunotherapy, but not during inhalation challenge, partially reversed the suppressive effects of immunotherapy on airway eosinophilia and TH2 cytokine levels, whereas airway hyperresponsiveness and serum OVA-specific IgE levels remained suppressed. Administration of tryptophan during immunotherapy failed to abrogate its beneficial effects toward allergic airway inflammation. Interestingly, administration of tryptophan or its metabolites, kynurenine, 3-hydroxykynurenine, and xanthurenic acid, but not 3-hydroxyanthranilinic acid, quinolinic acid, and kynurenic acid, during suboptimal immunotherapy potentiated the reduction of eosinophilia. These effects coincided with reduced TH2 cytokine levels in bronchoalveolar lavage fluid, but no effects on IgE levels were detected. During immunotherapy, the tryptophan metabolites kynurenine, 3-hydroxykynurenine, and xanthurenic acid generated through IDO contribute to tolerance induction regarding TH2-dependent allergic airway inflammation.

Buprenorphine dose induction in non-opioid-tolerant pre-release prisoners.

PubMed

Vocci, Frank J; Schwartz, Robert P; Wilson, Monique E; Gordon, Michael S; Kinlock, Timothy W; Fitzgerald, Terrence T; O'Grady, Kevin E; Jaffe, Jerome H

2015-11-01

In a previously reported randomized controlled trial, formerly opioid-dependent prisoners were more likely to enter community drug abuse treatment when they were inducted in prison onto buprenorphine/naloxone (hereafter called buprenorphine) than when they received counseling without buprenorphine in prison (47.5% vs. 33.7%, p=0.012) (Gordon et al., 2014). In this communication we report on the results of the induction schedule and the adverse event profile seen in pre-release prisoners inducted onto buprenorphine. This paper examines the dose induction procedure, a comparison of the proposed versus actual doses given per week, and side effects reported for 104 adult participants who were randomized to buprenorphine treatment in prison. Self-reported side effects were analyzed using generalized estimated equations to determine changes over time in side effects. Study participants were inducted onto buprenorphine at a rate faster than the induction schedule. Of the 104 (72 males, 32 females) buprenorphine recipients, 64 (37 males, 27 females) remained on medication at release from prison. Nine participants (8.6%) discontinued buprenorphine because of unpleasant opioid side effects. There were no serious adverse events reported during the in-prison phase of the study. Constipation was the most frequent symptom reported (69 percent). Our findings suggest that buprenorphine administered to non-opioid-tolerant adults should be started at a lower, individualized dose than customarily used for adults actively using opioids, and that non-opioid-tolerant pre-release prisoners can be successfully inducted onto therapeutic doses prior to release. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.