Composite Bipolar Plate for Unitized Fuel Cell/Electrolyzer Systems

Science.gov (United States)

Mittelsteadt, Cortney K.; Braff, William

2009-01-01

In a substantial improvement over present alkaline systems, an advanced hybrid bipolar plate for a unitized fuel cell/electrolyzer has been developed. This design, which operates on pure feed streams (H2/O2 and water, respectively) consists of a porous metallic foil filled with a polymer that has very high water transport properties. Combined with a second metallic plate, the pore-filled metallic plates form a bipolar plate with an empty cavity in the center.

Electrical coupling between A17 cells enhances reciprocal inhibitory feedback to rod bipolar cells.

Science.gov (United States)

Elgueta, Claudio; Leroy, Felix; Vielma, Alex H; Schmachtenberg, Oliver; Palacios, Adrian G

2018-02-15

A17 amacrine cells are an important part of the scotopic pathway. Their synaptic varicosities receive glutamatergic inputs from rod bipolar cells (RBC) and release GABA onto the same RBC terminal, forming a reciprocal feedback that shapes RBC depolarization. Here, using patch-clamp recordings, we characterized electrical coupling between A17 cells of the rat retina and report the presence of strongly interconnected and non-coupled A17 cells. In coupled A17 cells, evoked currents preferentially flow out of the cell through GJs and cross-synchronization of presynaptic signals in a pair of A17 cells is correlated to their coupling degree. Moreover, we demonstrate that stimulation of one A17 cell can induce electrical and calcium transients in neighboring A17 cells, thus confirming a functional flow of information through electrical synapses in the A17 coupled network. Finally, blocking GJs caused a strong decrease in the amplitude of the inhibitory feedback onto RBCs. We therefore propose that electrical coupling between A17 cells enhances feedback onto RBCs by synchronizing and facilitating GABA release from inhibitory varicosities surrounding each RBC axon terminal. GJs between A17 cells are therefore critical in shaping the visual flow through the scotopic pathway.

Alternative bipolar plates design and manufacturing for PEM fuel cell

International Nuclear Information System (INIS)

Lee Chang Chuan; Norhamidi Muhamad; Jaafar Sahari

2006-01-01

Bipolar plates is one of the important components in fuel cell stack, it comprise up to 80% of the stack volume. Traditionally, these plates have been fabricated from graphite, owing to its chemical nobility, and high electrical and thermal conductivity; but these plates are brittle and relatively thick. Therefore increasing the stack volume and size. Alternatives to graphite are carbon-carbon composite, carbon-polymer composite and metal (aluminum, stainless steel, titanium and nickel based alloy). The use of coated and uncoated metal bipolar plates has received attention recently due to the simplicity of plate manufacturing. The thin nature of the metal substrate allows for smaller stack design with reduced weight. Lightweight coated metals as alternative to graphite plate is being developed. Beside the traditional method of machining and slurry molding, metal foam for bipolar plates fabrication seems to be a good alternative. The plates will be produced with titanium powder by Powder Metallurgy method using space holders technique to produce the meal foam flow-field. This work intends to facilitate the materials and manufacturing process requirements to produce cost effective foamed bipolar plates for fuel cell

Asymmetry between ON and OFF α ganglion cells of mouse retina: integration of signal and noise from synaptic inputs.

Science.gov (United States)

Freed, Michael A

2017-11-15

Bipolar and amacrine cells presynaptic to the ON sustained α cell of mouse retina provide currents with a higher signal-to-noise power ratio (SNR) than those presynaptic to the OFF sustained α cell. Yet the ON cell loses proportionately more SNR from synaptic inputs to spike output than the OFF cell does. The higher SNR of ON bipolar cells at the beginning of the ON pathway compensates for losses incurred by the ON ganglion cell, and improves the processing of positive contrasts. ON and OFF pathways in the retina include functional pairs of neurons that, at first glance, appear to have symmetrically similar responses to brightening and darkening, respectively. Upon careful examination, however, functional pairs exhibit asymmetries in receptive field size and response kinetics. Until now, descriptions of how light-adapted retinal circuitry maintains a preponderance of signal over the noise have not distinguished between ON and OFF pathways. Here I present evidence of marked asymmetries between members of a functional pair of sustained α ganglion cells in the mouse retina. The ON cell exhibited a proportionately greater loss of signal-to-noise power ratio (SNR) from its presynaptic arrays to its postsynaptic currents. Thus the ON cell combines signal and noise from its presynaptic arrays of bipolar and amacrine cells less efficiently than the OFF cell does. Yet the inefficiency of the ON cell is compensated by its presynaptic arrays providing a higher SNR than the arrays presynaptic to the OFF cell, apparently to improve visual processing of positive contrasts. Dynamic clamp experiments were performed that introduced synaptic conductances into ON and OFF cells. When the amacrine-modulated conductance was removed, the ON cell's spike train exhibited an increase in SNR. The OFF cell, however, showed the opposite effect of removing amacrine input, which was a decrease in SNR. Thus ON and OFF cells have different modes of synaptic integration with direct effects on

Flow channel shape optimum design for hydroformed metal bipolar plate in PEM fuel cell

Energy Technology Data Exchange (ETDEWEB)

Peng, Linfa; Lai, Xinmin; Liu, Dong' an; Hu, Peng [State Key Laboratory of Mechanical System and Vibration, Shanghai Jiao Tong University, Shanghai 200240 (China); Ni, Jun [Department of Mechanical Engineering and Applied Mechanics, University of Michigan, Ann Arbor, MI 48109 (United States)

2008-03-15

Bipolar plate is one of the most important and costliest components of polymer electrolyte membrane (PEM) fuel cells. Micro-hydroforming is a promising process to reduce the manufacturing cost of PEM fuel cell bipolar plates made of metal sheets. As for hydroformed bipolar plates, the main defect is the rupture because of the thinning of metal sheet during the forming process. The flow channel section decides whether high quality hydroformed bipolar plates can be successively achieved or not. Meanwhile, it is also the key factor that is related with the reaction efficiency of the fuel cell stacks. In order to obtain the optimum flow channel section design prior the experimental campaign, some key geometric dimensions (channel depth, channel width, rib width and transition radius) of flow channel section, which are related with both reaction efficiency and formability, are extracted and parameterized as the design variables. By design of experiments (DOE) methods and an adoptive simulated annealing (ASA) optimization method, an optimization model of flow channel section design for hydroformed metal bipolar plate is proposed. Optimization results show that the optimum dimension values for channel depth, channel width, rib width and transition radius are 0.5, 1.0, 1. 6 and 0.5 mm, respectively with the highest reaction efficiency (79%) and the acceptable formability (1.0). Consequently, their use would lead to improved fuel cell efficiency for low cost hydroformed metal bipolar plates. (author)

The TRPM1 Channel Is Required for Development of the Rod ON Bipolar Cell-AII Amacrine Cell Pathway in the Retinal Circuit.

Science.gov (United States)

Kozuka, Takashi; Chaya, Taro; Tamalu, Fuminobu; Shimada, Mariko; Fujimaki-Aoba, Kayo; Kuwahara, Ryusuke; Watanabe, Shu-Ichi; Furukawa, Takahisa

2017-10-11

Neurotransmission plays an essential role in neural circuit formation in the central nervous system (CNS). Although neurotransmission has been recently clarified as a key modulator of retinal circuit development, the roles of individual synaptic transmissions are not yet fully understood. In the current study, we investigated the role of neurotransmission from photoreceptor cells to ON bipolar cells in development using mutant mouse lines of both sexes in which this transmission is abrogated. We found that deletion of the ON bipolar cation channel TRPM1 results in the abnormal contraction of rod bipolar terminals and a decreased number of their synaptic connections with amacrine cells. In contrast, these histological alterations were not caused by a disruption of total glutamate transmission due to loss of the ON bipolar glutamate receptor mGluR6 or the photoreceptor glutamate transporter VGluT1. In addition, TRPM1 deficiency led to the reduction of total dendritic length, branch numbers, and cell body size in AII amacrine cells. Activated Goα, known to close the TRPM1 channel, interacted with TRPM1 and induced the contraction of rod bipolar terminals. Furthermore, overexpression of Channelrhodopsin-2 partially rescued rod bipolar cell development in the TRPM1 -/- retina, whereas the rescue effect by a constitutively closed form of TRPM1 was lower than that by the native form. Our results suggest that TRPM1 channel opening is essential for rod bipolar pathway establishment in development. SIGNIFICANCE STATEMENT Neurotransmission has been recognized recently as a key modulator of retinal circuit development in the CNS. However, the roles of individual synaptic transmissions are not yet fully understood. In the current study, we focused on neurotransmission between rod photoreceptor cells and rod bipolar cells in the retina. We used genetically modified mouse models which abrogate each step of neurotransmission: presynaptic glutamate release, postsynaptic glutamate

Charge separation in excitonic and bipolar solar cells - A detailed balance approach

International Nuclear Information System (INIS)

Kirchartz, Thomas; Rau, Uwe

2008-01-01

A generalized solar cell model for excitonic and classical, bipolar solar cells is developed that describes the combined transport and interaction of electrons, holes and excitons. Both, conventional inorganic solar cells as well as organic solar cells, where excitons play a dominant role for energy transport, turn out to be special cases of this model. Due to the inclusion of photon recycling effects, the approach is compatible with the principle of detailed balance and the Shockley-Queisser limit. We show how varying the interaction between excitons and charge carriers as well as varying the respective mobilities of the different species changes the operation mode of the solar cell path between excitonic and bipolar

DeepBipolar: Identifying genomic mutations for bipolar disorder via deep learning.

Science.gov (United States)

Laksshman, Sundaram; Bhat, Rajendra Rana; Viswanath, Vivek; Li, Xiaolin

2017-09-01

Bipolar disorder, also known as manic depression, is a brain disorder that affects the brain structure of a patient. It results in extreme mood swings, severe states of depression, and overexcitement simultaneously. It is estimated that roughly 3% of the population of the United States (about 5.3 million adults) suffers from bipolar disorder. Recent research efforts like the Twin studies have demonstrated a high heritability factor for the disorder, making genomics a viable alternative for detecting and treating bipolar disorder, in addition to the conventional lengthy and costly postsymptom clinical diagnosis. Motivated by this study, leveraging several emerging deep learning algorithms, we design an end-to-end deep learning architecture (called DeepBipolar) to predict bipolar disorder based on limited genomic data. DeepBipolar adopts the Deep Convolutional Neural Network (DCNN) architecture that automatically extracts features from genotype information to predict the bipolar phenotype. We participated in the Critical Assessment of Genome Interpretation (CAGI) bipolar disorder challenge and DeepBipolar was considered the most successful by the independent assessor. In this work, we thoroughly evaluate the performance of DeepBipolar and analyze the type of signals we believe could have affected the classifier in distinguishing the case samples from the control set. © 2017 Wiley Periodicals, Inc.

Molecular pathways involved in neuronal cell adhesion and membrane scaffolding contribute to schizophrenia and bipolar disorder susceptibility.

LENUS (Irish Health Repository)

O'Dushlaine, C

2011-03-01

Susceptibility to schizophrenia and bipolar disorder may involve a substantial, shared contribution from thousands of common genetic variants, each of small effect. Identifying whether risk variants map to specific molecular pathways is potentially biologically informative. We report a molecular pathway analysis using the single-nucleotide polymorphism (SNP) ratio test, which compares the ratio of nominally significant (P<0.05) to nonsignificant SNPs in a given pathway to identify the \\'enrichment\\' for association signals. We applied this approach to the discovery (the International Schizophrenia Consortium (n=6909)) and validation (Genetic Association Information Network (n=2729)) of schizophrenia genome-wide association study (GWAS) data sets. We investigated each of the 212 experimentally validated pathways described in the Kyoto Encyclopaedia of Genes and Genomes in the discovery sample. Nominally significant pathways were tested in the validation sample, and five pathways were found to be significant (P=0.03-0.001); only the cell adhesion molecule (CAM) pathway withstood conservative correction for multiple testing. Interestingly, this pathway was also significantly associated with bipolar disorder (Wellcome Trust Case Control Consortium (n=4847)) (P=0.01). At a gene level, CAM genes associated in all three samples (NRXN1 and CNTNAP2), which were previously implicated in specific language disorder, autism and schizophrenia. The CAM pathway functions in neuronal cell adhesion, which is critical for synaptic formation and normal cell signaling. Similar pathways have also emerged from a pathway analysis of autism, suggesting that mechanisms involved in neuronal cell adhesion may contribute broadly to neurodevelopmental psychiatric phenotypes.

Fabrication of carbon-polymer composite bipolar plates for polymer electrolyte membrane fuel cells by compression moulding

International Nuclear Information System (INIS)

Raza, M.A.; Ahmed, R.; Saleem, A.; Din, R.U.

2009-01-01

Fuel cells are considered as one of the most important technologies to address the future energy and environmental pollution problems. These are the most promising power sources for road transportation and portable devices. A fuel cell is an electrochemical device that converts chemical energy into electrical energy. A fuel cell stack consists of bipolar plates and membrane electrode assemblies (MEA). The bipolar plate is by weight, volume and cost one of the most significant components of a fuel cell stack. Major functions of bipolar plates are to separate oxidant and fuel gas, provide flow channels, conduct electricity and provide heat transfer. Bipolar plates can be made from various materials including graphite, metals, carbon / carbon and carbon/ polymer composites. Materials for carbon-polymer composites are relatively inexpensive, less corrosive, strong and channels can be formed by means of a moulding process. Carbon-polymer composites are of two type i.e; thermosetting and thermoplastic. For thermosetting composite a bulk molding compound (BMC) was prepared by adding graphite, vinyl ester resin, methyl ethyl ketone peroxide and cobalt naphthalate. The BMC was thoroughly mixed, poured into a die mould of a bipolar plate with channels and hot pressed at a specific temperature and pressure. A bipolar plate was formed according to the die mould. Design of the mould is also discussed. Conducting polymers were also added to BMC to increase the conductivity of bipolar plates. Particle size of the graphite has also a significant effect on the conductivity of the bipolar plates. Thermoplastic composites were also prepared using polypropylene and graphite.

Evaluation of bistable systems versus matched filters in detecting bipolar pulse signals

OpenAIRE

Duan, Fabing; Abbott, Derek; Gao, Qisheng

2004-01-01

This paper presents a thorough evaluation of a bistable system versus a matched filter in detecting bipolar pulse signals. The detectability of the bistable system can be optimized by adding noise, i.e. the stochastic resonance (SR) phenomenon. This SR effect is also demonstrated by approximate statistical detection theory of the bistable system and corresponding numerical simulations. Furthermore, the performance comparison results between the bistable system and the matched filter show that...

Test Results of a Ten Cell Bipolar Nickel-hydrogen Battery

Science.gov (United States)

Cataldo, R. L.

1984-01-01

A study was initiated to design and evaluate a new design concept for nickel-hydrogen cells. This concept involved constructing a battery in a bipolar stack with cells consisting of a one plate for each nickel and hydrogen electrode. Preliminary designs at the system level of this concept promised improvements in both volumetric and gravimetric energy densities, thermal management, life extension, costs, and peak power capability over more conventional designs. Test results were most encouraging. This preprototype battery, built with less than ideal components and hardware, exceeded expectations. A total of 2000 LEO cycles at 80 percent depth of discharge were accrued. A cycle life goal of 30,000 cycles appears achievable with minor design changes. These improvements include advanced technology nickel electrodes, insulated bipolar plates and specifically designed frames to minimize shunt currents. The discharge rate capability of this design exceeds 25C. At the 10C discharge rate, 80% of the battery capacity can be withdrawn in six minutes. This data shows that the bipolar design is well suited for those applications requiring high peak power pulses.

Unraveling the biology of bipolar disorder using induced pluripotent stem-derived neurons.

Science.gov (United States)

Miller, Nathaniel D; Kelsoe, John R

2017-11-01

Bipolar disorder has been studied from numerous angles, from pathological studies to large-scale genomic studies, overall making moderate gains toward an understanding of the disorder. With the advancement of induced pluripotent stem (iPS) cell technology, in vitro models based on patient samples are now available that inherently incorporate the complex genetic variants that largely are the basis for this disorder. A number of groups are starting to apply iPS technology to the study of bipolar disorder. We selectively reviewed the literature related to understanding bipolar disorder based on using neurons derived from iPS cells. So far, most work has used the prototypical iPS cells. However, others have been able to transdifferentiate fibroblasts directly to neurons. Others still have utilized olfactory epithelium tissue as a source of neural-like cells that do not need reprogramming. In general, iPS and related cells can be used for studies of disease pathology, drug discovery, or stem cell therapy. Published studies have primarily focused on understanding bipolar disorder pathology, but initial work is also being done to use iPS technology for drug discovery. In terms of disease pathology, some evidence is pointing toward a differentiation defect with more ventral cell types being prominent. Additionally, there is evidence for a calcium signaling defect, a finding that builds on the genome-wide association study results. Continued work with iPS cells will certainly help us understand bipolar disorder and provide a way forward for improved treatments. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Bipolar Plates for PEM Systems

OpenAIRE

Lædre, Sigrid

2016-01-01

Summary of thesis: The Bipolar Plate (BPP) is an important component in both Proton Exchange Membrane Fuel Cells (PEMFCs) and Proton Exchange Membrane Water Electrolyzers (PEMWEs). Bipolar plate material and processing constitutes for a large fraction of the cost and weight of a PEM cell stack. The main tasks for the bipolar plates in both systems are to separate single cell in a stack, conduct current between single cells and remove heat from active areas. In addition, the BPPs distribu...

Corrosion of metal bipolar plates for PEM fuel cells: A review

Energy Technology Data Exchange (ETDEWEB)

Antunes, Renato A. [Engenharia de Materiais, Universidade Federal do ABC (UFABC), 09210-170 Santo Andre, SP (Brazil); Oliveira, Mara Cristina L.; Ett, Gerhard; Ett, Volkmar [Electrocell Ind. Com. Equip. Elet. LTDA, Centro de Inovacao, Empreendedorismo e Tecnologia (CIETEC), 05508-000 Sao Paulo, SP (Brazil)

2010-04-15

PEM fuel cells are of prime interest in transportation applications due to their relatively high efficiency and low pollutant emissions. Bipolar plates are the key components of these devices as they account for significant fractions of their weight and cost. Metallic materials have advantages over graphite-based ones because of their higher mechanical strength and better electrical conductivity. However, corrosion resistance is a major concern that remains to be solved as metals may develop oxide layers that increase electrical resistivity, thus lowering the fuel cell efficiency. This paper aims to present the main results found in recent literature about the corrosion performance of metallic bipolar plates. (author)

SEU-hardened silicon bipolar and GaAs MESFET SRAM cells using local redundancy techniques

International Nuclear Information System (INIS)

Hauser, J.R.

1992-01-01

Silicon bipolar and GaAs FET SRAM's have proven to be more difficult to harden with respect to single-event upset mechanisms than have silicon CMOS SRAM's. This is a fundamental property of bipolar and JFET or MESFET device technologies which do not have a high-impedance, nonactive isolation between the control electrode and the current or voltage being controlled. All SEU circuit level hardening techniques applied at the local level must use some type of information storage redundancy so that information loss on one node due to an SEU event can be recovered from information stored elsewhere in the cell. In CMOS technologies, this can be achieved by the use of simple cross-coupling resistors, whereas in bipolar and FET technologies, no such simple approach is possible. Several approaches to the use of local redundancy in bipolar and FET technologies are discussed in this paper. At the expense of increased cell complexity and increased power consumption and write time, several approaches are capable of providing complete SEU hardness at the local cell level

Development and degeneration of cone bipolar cells are independent of cone photoreceptors in a mouse model of retinitis pigmentosa.

Directory of Open Access Journals (Sweden)

Miao Chen

Full Text Available Retinal photoreceptors die during retinal synaptogenesis in a portion of retinal degeneration. Whether cone bipolar cells establish regular retinal mosaics and mature morphologies, and resist degeneration are not completely understood. To explore these issues, we backcrossed a transgenic mouse expressing enhanced green fluorescent protein (EGFP in one subset of cone bipolar cells (type 7 into rd1 mice, a classic mouse model of retinal degeneration, to examine the development and survival of cone bipolar cells in a background of retinal degeneration. Our data revealed that both the development and degeneration of cone bipolar cells are independent of the normal activity of cone photoreceptors. We found that type 7 cone bipolar cells achieved a uniform tiling of the retinal surface and developed normal dendritic and axonal arbors without the influence of cone photoreceptor innervation. On the other hand, degeneration of type 7 cone bipolar cells, contrary to our belief of central-to-peripheral progression, was spatially uniform across the retina independent of the spatiotemporal pattern of cone degeneration. The results have important implications for the design of more effective therapies to restore vision in retinal degeneration.

Design of metallic bipolar plates for PEM fuel cells.

Science.gov (United States)

2012-01-01

This project focused on the design and production of metallic bipolar plates for use in PEM fuel cells. Different metals were explored : and stainless steel was found out to be best suited to our purpose. Following the selection of metal, it was calc...

Potentiating action of propofol at GABAA receptors of retinal bipolar cells

DEFF Research Database (Denmark)

Yue, Lan; Xie, An; Bruzik, Karol S

2011-01-01

Purpose. Propofol (2,6-diisopropyl phenol), a widely used systemic anesthetic, is known to potentiate GABA(A) receptor activity in a number of CNS neurons and to produce changes in electroretinographically recorded responses of the retina. However, little is known about propofol's effects...... on specific retinal neurons. The authors investigated the action of propofol on GABA-elicited membrane current responses of retinal bipolar cells, which have both GABA(A) and GABA(C) receptors. Methods. Single, enzymatically dissociated bipolar cells obtained from rat retina were treated with propofol...... + propofol) led to a progressive increase in peak response amplitude and, at higher propofol concentrations, additional changes that included a prolonged time course of response recovery. Pre-exposure of the cell to perfusing propofol typically enhanced the rate of development of potentiation produced...

Nanosized TiN-SBR hybrid coating of stainless steel as bipolar plates for polymer electrolyte membrane fuel cells

International Nuclear Information System (INIS)

Kumagai, Masanobu; Myung, Seung-Taek; Asaishi, Ryo; Sun, Yang-Kook; Yashiro, Hitoshi

2008-01-01

In attempt to improve interfacial electrical conductivity of stainless steel for bipolar plates of polymer electrolyte membrane fuel cells, TiN nanoparticles were electrophoretically deposited on the surface of stainless steel with elastic styrene butadiene rubber (SBR) particles. From transmission electron microscopic observation, it was found that the TiN nanoparticles (ca. 50 nm) surrounded the spherical SBR particles (ca. 300-600 nm), forming agglomerates. They were well adhered on the surface of the type 310S stainless steel. With help of elasticity of SBR, the agglomerates were well fitted into the interfacial gap between gas diffusion layer (GDL) and stainless steel bipolar plate, and the interfacial contact resistance (ICR), simultaneously, was successfully reduced. A single cell using the TiN nanoparticles-coated bipolar plates, consequently, showed comparable cell performance with the graphite employing cell at a current density of 0.5 A cm -2 (12.5 A). Inexpensive TiN nanoparticle-coated type 310S stainless steel bipolar plates would become a possible alternate for the expensive graphite bipolar plates as use in fuel cell applications

Corrosion resistance characteristics of stamped and hydroformed proton exchange membrane fuel cell metallic bipolar plates

Energy Technology Data Exchange (ETDEWEB)

Dundar, F. [NSF I/UCRC Center for Precision Forming (CPF), Virginia Commonwealth University, Richmond, VA (United States); Department of Materials Science and Engineering, Gebze Institute of Technology (Turkey); Dur, Ender; Koc, M. [NSF I/UCRC Center for Precision Forming (CPF), Virginia Commonwealth University, Richmond, VA (United States); Mahabunphachai, S. [NSF I/UCRC Center for Precision Forming (CPF), Virginia Commonwealth University, Richmond, VA (United States); National Metal and Materials Technology Center (MTEC), Pathumthani (Thailand)

2010-06-01

Metallic bipolar plates have several advantages over bipolar plates made from graphite and composites due to their high conductivity, low material and production costs. Moreover, thin bipolar plates are possible with metallic alloys, and hence low fuel cell stack volume and mass are. Among existing fabrication methods for metallic bipolar plates, stamping and hydroforming are seen as prominent approaches for mass production scales. In this study, the effects of important process parameters of these manufacturing processes on the corrosion resistance of metallic bipolar plates made of SS304 were investigated. Specifically, the effects of punch speed, pressure rate, stamping force and hydroforming pressure were studied as they were considered to inevitably affect the bipolar plate micro-channel dimensions, surface topography, and hence the corrosion resistance. Corrosion resistance under real fuel cell conditions was examined using both potentiodynamic and potentiostatic experiments. The majority of the results exhibited a reduction in the corrosion resistance for both stamped and hydroformed plates when compared with non-deformed blank plates of SS304. In addition, it was observed that there exist an optimal process window for punch speed in stamping and the pressure rate in hydroforming to achieve improved corrosion resistance at a faster production rate. (author)

Photovoltaic Cells Improvised With Used Bipolar Junction Transistors

International Nuclear Information System (INIS)

Akintayo, J. A

2002-01-01

The understanding of the underlying principle that the solar cell consists of a p-n junction is exploited to adapt the basic NPN or PNP Bipolar Junction Transistors (BJT) to serve as solar cells. In this mode the in improvised solar cell have employed just the emitter and the base sections with an intact emitter/base junction as the active PN area. The improvised devices tested screened and sorted are wired up in strings, blocks and modules. The photovoltaic modules realised tested as close replica of solar cells with output voltage following insolation level. Further work need be done on the modules to make them generate usable levels of output voltage and current

Serum TRPM1 autoantibodies from melanoma associated retinopathy patients enter retinal on-bipolar cells and attenuate the electroretinogram in mice.

Directory of Open Access Journals (Sweden)

Wei-Hong Xiong

Full Text Available Melanoma-associated retinopathy (MAR is a paraneoplastic syndrome associated with cutaneous malignant melanoma and the presence of autoantibodies that label neurons in the inner retina. The visual symptoms and electroretinogram (ERG phenotype characteristic of MAR resemble the congenital visual disease caused by mutations in TRPM1, a cation channel expressed by both melanocytes and retinal bipolar cells. Four serum samples from MAR patients were identified as TRPM1 immunoreactive by 1. Labeling of ON-bipolar cells in TRPM1+/+ but not TRPM1-/- mouse retina, 2. Labeling of TRPM1-transfected CHO cells; and 3. Attenuation of the ERG b-wave following intravitreal injection of TRPM1-positive MAR IgG into wild-type mouse eyes, and the appearance of the IgG in the retinal bipolar cells at the conclusion of the experiment. Furthermore, the epitope targeted by the MAR autoantibodies was localized within the amino-terminal cytoplasmic domain of TRPM1. Incubation of live retinal neurons with TRPM1-positive MAR serum resulted in the selective accumulation of IgG in ON-bipolar cells from TRPM1+/+ mice, but not TRPM1-/- mice, suggesting that the visual deficits in MAR are caused by the uptake of TRPM1 autoantibodies into ON-bipolar cells, where they bind to an intracellular epitope of the channel and reduce the ON-bipolar cell response to light.

Requirements and testing methods for surfaces of metallic bipolar plates for low-temperature PEM fuel cells

Science.gov (United States)

Jendras, P.; Lötsch, K.; von Unwerth, T.

2017-03-01

To reduce emissions and to substitute combustion engines automotive manufacturers, legislature and first users aspire hydrogen fuel cell vehicles. Up to now the focus of research was set on ensuring functionality and increasing durability of fuel cell components. Therefore, expensive materials were used. Contemporary research and development try to substitute these substances by more cost-effective material combinations. The bipolar plate is a key component with the greatest influence on volume and mass of a fuel cell stack and they have to meet complex requirements. They support bending sensitive components of stack, spread reactants over active cell area and form the electrical contact to another cell. Furthermore, bipolar plates dissipate heat of reaction and separate one cell gastight from the other. Consequently, they need a low interfacial contact resistance (ICR) to the gas diffusion layer, high flexural strength, good thermal conductivity and a high durability. To reduce costs stainless steel is a favoured material for bipolar plates in automotive applications. Steel is characterized by good electrical and thermal conductivity but the acid environment requires a high chemical durability against corrosion as well. On the one hand formation of a passivating oxide layer increasing ICR should be inhibited. On the other hand pitting corrosion leading to increased permeation rate may not occur. Therefore, a suitable substrate lamination combination is wanted. In this study material testing methods for bipolar plates are considered.

Nicotinic receptors and functional regulation of GABA cell microcircuitry in bipolar disorder and schizophrenia.

Science.gov (United States)

Benes, Francine M

2012-01-01

Studies of the hippocampus in postmortem brains from patients with schizophrenia and bipolar disorder have provided evidence for a defect of GABAergic interneurons. Significant decreases in the expression of GAD67, a marker for GABA cell function, have been found repeatedly in several different brain regions that include the hippocampus. In this region, nicotinic receptors are thought to play an important role in modulating the activity of GABAergic interneurons by influences of excitatory cholinergic afferents on their activity. In bipolar disorder, this influence appears to be particularly prominent in the stratum oriens of sectors CA3/2 and CA1, two sites where these cells constitute the exclusive neuronal cell type. In sector CA3/2, this layer receives a robust excitatory projection from the basolateral amygdala (BLA) and this is thought to play a central role in regulating GABA cells at this locus. Using laser microdissection, recent studies have focused selectively on these two layers and their associated GABA cells using microarray technology. The results have provided support for the idea that nicotinic cholinergic receptors play a particularly important role in regulating the activity of GABA neurons at these loci by regulating the progression of cell cycle and the repair of damaged DNA. In bipolar disorder, there is a prominent reduction in the expression of mRNAs for several different nicotinic subunit isoforms. These decreases could reflect a diminished influence of this receptor system on these GABA cells, particularly in sector CA3/2 where a preponderance of abnormalities have been observed in postmortem studies. In patients with bipolar disorder, excitatory nicotinic cholinergic fibers from the medial septum may converge with glutamatergic fibers from the BLA on GABAergic interneurons in the stratum oriens of CA3/2 and result in disturbances of their genomic and functional integrity, ones that may induce disruptions of the integration of

High rate lithium/thionyl chloride bipolar battery development

Science.gov (United States)

Russell, P. G.; Goebel, F.

The lithium/thionyl chloride ( {Li}/{SOCl2}) electrochemistry is capable of providing high power and high specific power, especially under pulse discharge conditions, when cells containing thin components are arranged in a bipolar configuration. This paper describes recent work concerned with bipolar cell design, cathode evaluation, component manufacturing methods, and the assembly and testing of bipolar modules containing up to 150 cells for Sonobuoy application.

High rate lithium/thionyl chloride bipolar battery development

Energy Technology Data Exchange (ETDEWEB)

Russell, P.G. [Yardney Technical Products, Inc., Pawcatuck, CT (United States); Goebel, F. [Yardney Technical Products, Inc., Pawcatuck, CT (United States)

1995-04-01

The lithium/thionyl chloride (Li/SOCl{sub 2}) electrochemistry is capable of providing high power and high specific power, especially under pulse discharge conditions, when cells containing thin components are arranged in a bipolar configuration. This paper describes recent work concerned with bipolar cell design, cathode evaluation, component manufacturing methods, and the assembly and testing of bipolar modules containing up to 150 cells for Sonobuoy application. (orig.)

Highly conductive composites for fuel cell flow field plates and bipolar plates

Science.gov (United States)

Jang, Bor Z; Zhamu, Aruna; Song, Lulu

2014-10-21

This invention provides a fuel cell flow field plate or bipolar plate having flow channels on faces of the plate, comprising an electrically conductive polymer composite. The composite is composed of (A) at least 50% by weight of a conductive filler, comprising at least 5% by weight reinforcement fibers, expanded graphite platelets, graphitic nano-fibers, and/or carbon nano-tubes; (B) polymer matrix material at 1 to 49.9% by weight; and (C) a polymer binder at 0.1 to 10% by weight; wherein the sum of the conductive filler weight %, polymer matrix weight % and polymer binder weight % equals 100% and the bulk electrical conductivity of the flow field or bipolar plate is at least 100 S/cm. The invention also provides a continuous process for cost-effective mass production of the conductive composite-based flow field or bipolar plate.

High rate lithium-thionyl chloride bipolar battery development

Energy Technology Data Exchange (ETDEWEB)

Russell, P.G.; Goebel, F. [Yardney Technical Products, Inc., Pawcatuck, CT (United States)

1994-12-31

The lithium/thionyl chloride system is capable of providing both high power and high energy density when cells containing thin components are arranged in a bipolar configuration. Electrode current densities in excess of 300mA/cm{sup 2} are achieved during pulse discharge. The present work is concerned with bipolar cell design, cathode evaluation, component manufacturing methods, and the assembly and testing of bipolar modules containing up to 150 cells.

Bipolar soft connected, bipolar soft disconnected and bipolar soft compact spaces

Directory of Open Access Journals (Sweden)

Muhammad Shabir

2017-06-01

Full Text Available Bipolar soft topological spaces are mathematical expressions to estimate interpretation of data frameworks. Bipolar soft theory considers the core features of data granules. Bipolarity is important to distinguish between positive information which is guaranteed to be possible and negative information which is forbidden or surely false. Connectedness and compactness are the most important fundamental topological properties. These properties highlight the main features of topological spaces and distinguish one topology from another. Taking this into account, we explore the bipolar soft connectedness, bipolar soft disconnectedness and bipolar soft compactness properties for bipolar soft topological spaces. Moreover, we introduce the notion of bipolar soft disjoint sets, bipolar soft separation, and bipolar soft hereditary property and study on bipolar soft connected and disconnected spaces. By giving the detailed picture of bipolar soft connected and disconnected spaces we investigate bipolar soft compact spaces and derive some results related to this concept.

Localization of Rod Bipolar Cells in the Mammalian Retina Using an Antibody Against the α1c L-type Ca2+ Channel

International Nuclear Information System (INIS)

Huh, Yu-Jin; Choi, Jae-Sik; Jeon, Chang-Jin

2015-01-01

Bipolar cells transmit stimuli via graded changes in membrane potential and neurotransmitter release is modulated by Ca 2+ influx through L-type Ca 2+ channels. The purpose of this study was to determine whether the α 1 c subunit of L-type voltage-gated Ca 2+ channel (α 1 c L-type Ca 2+ channel) colocalizes with protein kinase C alpha (PKC-α), which labels rod bipolar cells. Retinal whole mounts and vertical sections from mouse, hamster, rabbit, and dog were immunolabeled with antibodies against PKC-α and α 1 c L-type Ca 2+ channel, using fluorescein isothiocyanate (FITC) and Cy5 as visualizing agents. PKC-α-immunoreactive cells were morphologically identical to rod bipolar cells as previously reported. Their cell bodies were located within the inner nuclear layer, dendritic processes branched into the outer plexiform layer, and axons extended into the inner plexiform layer. Immunostaining showed that α 1 c L-type Ca 2+ channel colocalized with PKC-α in rod bipolar cells. The identical expression of PKC-α and α 1 c L-type Ca 2+ channel indicates that the α 1 c L-type Ca 2+ channel has a specific role in rod bipolar cells, and the antibody against the α 1 c L-type Ca 2+ channel may be a useful marker for studying the distribution of rod bipolar cells in mouse, hamster, rabbit, and dog retinas

Mef2d is essential for the maturation and integrity of retinal photoreceptor and bipolar cells.

Science.gov (United States)

Omori, Yoshihiro; Kitamura, Tamiki; Yoshida, Satoyo; Kuwahara, Ryusuke; Chaya, Taro; Irie, Shoichi; Furukawa, Takahisa

2015-05-01

Mef2 transcription factors play a crucial role in cardiac and skeletal muscle differentiation. We found that Mef2d is highly expressed in the mouse retina and its loss causes photoreceptor degeneration similar to that observed in human retinitis pigmentosa patients. Electroretinograms (ERGs) were severely impaired in Mef2d-/- mice. Immunohistochemistry showed that photoreceptor and bipolar cell synapse protein levels severely decreased in the Mef2d-/- retina. Expression profiling by microarray analysis showed that Mef2d is required for the expression of various genes in photoreceptor and bipolar cells, including cone arrestin, Guca1b, Pde6h and Cacna1s, which encode outer segment and synapse proteins. We also observed that Mef2d synergistically activates the cone arrestin (Arr3) promoter with Crx, suggesting that functional cooperation between Mef2d and Crx is important for photoreceptor cell gene regulation. Taken together, our results show that Mef2d is essential for photoreceptor and bipolar cell gene expression, either independently or cooperatively with Crx. © 2015 Institution for Protein Research. Genes to Cells published by Wiley Publishing Asia Pty Ltd and the Molecular Biology Society of Japan.

Process for production of electrical energy from the neutralization of acid and base in a bipolar membrane cell

International Nuclear Information System (INIS)

Walther, J.F.

1982-01-01

Electrical energy is generated from acid-base neutralization reactions in electrodialytic cells. Permselective bipolar membranes in these cells are contacted on their cation selective faces by aqueous acid streams and on their anion-selective faces by aqueous base streams. Spontaneous neutralization reactions between the basic anions and acidic cations through the bipolar membranes produce electrical potential differences between the acid and base streams. These potential differences are transmitted to electrodes to produce electrical energy which is withdrawn from the cell

Acetylcholine induces GABA release onto rod bipolar cells through heteromeric nicotinic receptors expressed in A17 amacrine cells.

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Elgueta, Claudio; Vielma, Alex H; Palacios, Adrian G; Schmachtenberg, Oliver

2015-01-01

Acetylcholine (ACh) is a major retinal neurotransmitter that modulates visual processing through a large repertoire of cholinergic receptors expressed on different retinal cell types. ACh is released from starburst amacrine cells (SACs) under scotopic conditions, but its effects on cells of the rod pathway have not been investigated. Using whole-cell patch clamp recordings in slices of rat retina, we found that ACh application triggers GABA release onto rod bipolar (RB) cells. GABA was released from A17 amacrine cells and activated postsynaptic GABAA and GABAC receptors in RB cells. The sensitivity of ACh-induced currents to nicotinic ACh receptor (nAChR) antagonists (TMPH ~ mecamylamine > erysodine > DhβE > MLA) together with the differential potency of specific agonists to mimic ACh responses (cytisine > RJR2403 ~ choline), suggest that A17 cells express heteromeric nAChRs containing the β4 subunit. Activation of nAChRs induced GABA release after Ca(2+) accumulation in A17 cell dendrites and varicosities mediated by L-type voltage-gated calcium channels (VGCCs) and intracellular Ca(2+) stores. Inhibition of acetylcholinesterase depolarized A17 cells and increased spontaneous inhibitory postsynaptic currents in RB cells, indicating that endogenous ACh enhances GABAergic inhibition of RB cells. Moreover, injection of neostigmine or cytisine reduced the b-wave of the scotopic flash electroretinogram (ERG), suggesting that cholinergic modulation of GABA release controls RB cell activity in vivo. These results describe a novel regulatory mechanism of RB cell inhibition and complement our understanding of the neuromodulatory control of retinal signal processing.

Bipolar nickel-hydrogen battery development - A program review

Science.gov (United States)

Manzo, Michelle; Lenhart, Stephen; Hall, Arnold

1989-01-01

An overview of spacecraft power system design trends, focusing on higher power bus voltages and improved energy storage systems, is followed by a discussion of bipolar Ni/H2 battery development efforts. Several 10-cell batteries and one 50-cell battery are described, and performance results are presented. A comparison of individual-pressure-vessel and bipolar Ni/H2 technologies is used to suggest a new direction for bipolar Ni/H2 battery development efforts, toward a large number of passively cooled cells in parallel.

Low cost bipolar current collector-separator for electrochemical cells

International Nuclear Information System (INIS)

Lawrence, R.

1980-01-01

A bipolar current collecting, cell separating element for electrochemical cells for conducting current from the anode electrode of one cell unit to cathode electrode of the adjacent cell unit comprises: (A) a pressure mold aggregate of electrically conductive carbon/graphite particles and thermoplastic fluorocarbon polymer resin particles in a weight ratio of 2.5:1 to 16:1 whereby said molded aggregated has a bulk resistivity which is less than 4x10 -3 ohm/inch, (B) said molded aggregate having a fluid imprevious main body, at least one recessed chamber on one side of said main body and a plurality of spaced, conductive projections extending from the base of said chamber for contacting and permitting current flow between the electrode of adjacent cell unit, and (C) means communicating with said recessed chambers to permit introduction and removal of fluids

2017 Bipolar Plate Workshop Summary Report

Energy Technology Data Exchange (ETDEWEB)

Kopasz, John P. [Argonne National Lab. (ANL), Argonne, IL (United States); Benjamin, Thomas G. [Argonne National Lab. (ANL), Argonne, IL (United States); Schenck, Deanna [Argonne National Lab. (ANL), Argonne, IL (United States)

2017-08-17

The Bipolar Plate (BP) Workshop was held at USCAR1 in Southfield, Michigan on February 14, 2017 and included 63 participants from industry, government agencies, universities, and national laboratories with expertise in the relevant fields. The objective of the workshop was to identify research and development (R&D) needs, in particular early-stage R&D, for bipolar plates for polymer electrolyte membrane (PEM) fuel cells for transportation applications. The focus of the workshop was on materials, manufacturing, and design aspects of bipolar plates with the goal of meeting DOE’s 2020 bipolar plate targets. Of special interest was the cost target of ≤$3/kW for the bipolar plate.

Reviewing metallic PEMFC bipolar plates

Energy Technology Data Exchange (ETDEWEB)

Wang, H.; Turner, J.A. [National Renewable Energy Laboratory, Golden, CO (United States)

2010-08-15

A bipolar plate is one of the most important components in a polymer exchange membrane fuel cell (PEMFC) stack and has multiple functions. Metallic bipolar plate candidates have advantages over composite rivals in excellent electrical and thermal conductivity, good mechanical strength, high chemical stability, very wide alloy choices, low cost and, most importantly, existing pathways for high-volume, high-speed mass production. The challenges with metallic bipolar plates are the higher contact resistance and possible corrosion products, which may contaminate the membrane electrode assembly. This review evaluates the candidate metallic and coating materials for bipolar plates and gives the perspective of the research trends. (Abstract Copyright [2010], Wiley Periodicals, Inc.)

Assessing Granger Causality in Electrophysiological Data: Removing the Adverse Effects of Common Signals via Bipolar Derivations.

Science.gov (United States)

Trongnetrpunya, Amy; Nandi, Bijurika; Kang, Daesung; Kocsis, Bernat; Schroeder, Charles E; Ding, Mingzhou

2015-01-01

Multielectrode voltage data are usually recorded against a common reference. Such data are frequently used without further treatment to assess patterns of functional connectivity between neuronal populations and between brain areas. It is important to note from the outset that such an approach is valid only when the reference electrode is nearly electrically silent. In practice, however, the reference electrode is generally not electrically silent, thereby adding a common signal to the recorded data. Volume conduction further complicates the problem. In this study we demonstrate the adverse effects of common signals on the estimation of Granger causality, which is a statistical measure used to infer synaptic transmission and information flow in neural circuits from multielectrode data. We further test the hypothesis that the problem can be overcome by utilizing bipolar derivations where the difference between two nearby electrodes is taken and treated as a representation of local neural activity. Simulated data generated by a neuronal network model where the connectivity pattern is known were considered first. This was followed by analyzing data from three experimental preparations where a priori predictions regarding the patterns of causal interactions can be made: (1) laminar recordings from the hippocampus of an anesthetized rat during theta rhythm, (2) laminar recordings from V4 of an awake-behaving macaque monkey during alpha rhythm, and (3) ECoG recordings from electrode arrays implanted in the middle temporal lobe and prefrontal cortex of an epilepsy patient during fixation. For both simulation and experimental analysis the results show that bipolar derivations yield the expected connectivity patterns whereas the untreated data (referred to as unipolar signals) do not. In addition, current source density signals, where applicable, yield results that are close to the expected connectivity patterns, whereas the commonly practiced average re-reference method

G Protein-Linked Signaling Pathways in Bipolar and Major Depressive Disorders

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Hiroaki eTomita

2013-12-01

Full Text Available The G-protein linked signaling system (GPLS comprises a large number of G-proteins, G protein-coupled receptors (GPCRs, GPCR ligands, and downstream effector molecules. G-proteins interact with both GPCRs and downstream effectors such as cyclic adenosine monophosphate (cAMP, phosphatidylinositols, and ion channels. The GPLS is implicated in the pathophysiology and pharmacology of both major depressive disorder (MDD and bipolar disorder (BPD. This study evaluated whether GPLS is altered at the transcript level. The gene expression in the dorsolateral prefrontal (DLPFC and anterior cingulate (ACC were compared from MDD, BPD, and control subjects using Affymetrix Gene Chips and real time quantitative PCR. High quality brain tissue was used in the study to control for confounding effects of agonal events, tissue pH, RNA integrity, gender, and age. GPLS signaling transcripts were altered especially in the ACC of BPD and MDD subjects. Transcript levels of molecules which repress cAMP activity were increased in BPD and decreased in MDD. Two orphan GPCRs, GPRC5B and GPR37, showed significantly decreased expression levels in MDD, and significantly increased expression levels in BPD. Our results suggest opposite changes in BPD and MDD in the GPLS, ‘activated’ cAMP signaling activity in BPD and ‘blunted’ cAMP signaling activity in MDD. GPRC5B and GPR37 both appear to have behavioral effects, and are also candidate genes for neurodegenerative disorders. In the context of the opposite changes observed in BPD and MDD, these GPCRs warrant further study of their brain effects.

Surface roughness effect on the metallic bipolar plates of a proton exchange membrane fuel cell

International Nuclear Information System (INIS)

Lin, Chien-Hung

2013-01-01

Highlights: ► Various degrees of roughness are caused by the sandblasting method. ► An improper surface modification depletes the PEMFC performance severely. ► The AC impedance are used to assess the fuel gas transfer effect. ► The Warburg resistance form in the coarse flow channel surface. - Abstract: Proton exchange membrane fuel cells (PEMFCs) is a promising candidate as energy systems. However, the stability and lifetime of cells are still important issues. The effect of surface roughness on metallic bipolar plate is discussed in this paper. Various roughness on the bulk surface are obtained by the sandblasting method. The grain sizes of sand are selected as 50, 100 and 200 μm. The Ac impedance experiment results show that the bipolar plate roughness and carbon paper porosity are well matched when the surface roughness is within 1–2 μm. Superior condition decreases the contact resistance loss in the fuel cell. The high frequency resistance of the coarse surface was larger than that of the substrate by around 5 mΩ. Furthermore, a new arc was formed at the low frequency region. Hence, the unmatch roughness condition of the bipolar plate significantly increases the contact resistance and mass transfer resistance. This paper develops a sequential approach to study an optimum surface roughness by combining the whole performance (I–V) curve and AC impedance result. It benefits us to quantify the contact and mass transfer resistance exists in the PEMFC. The proposed surface treatment improves the surface effect and promotes the implement of potential metallic bipolar plate in near future

Konduktifitas Listrik Komposit Polimer Polipropilena/Karbon Untuk Aplikasi Pelat Bipolar Fuel Cell

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Agus Pramono

2016-02-01

Full Text Available Proton exchange membrane fuel cell (PEMFC merupakan salah satu sumber energi alternatif yang saat ini sedang dikembangkan untuk mengatasi permasahan krisis energi dan lingkungan. Salah satu komponen yang mempunyai peran  signifikan dalam efisiensi biaya dan proses PEMFC adalah pelat bipolar. Untuk itu diperlukan pelat bipolar yang ringan, murah, dan mudah diproduksi secara masal. Dalam penelitian ini dikembangkan komposit pelat bipolar menggunakan matriks polipropilena (PP, penguat karbon hitam dan grafit elektroda dengan variasi komposisi wt% PP/grafit/CB sebesar 85:10:5; 75:20:5; 65:30:5;dan 55:40:5, sehingga mendapatkan sifat daya hantar listrik yang baik. Sifat-sifat dari komposit yang dihasilkan diuji dengan pengujian konduktivitas, Dari keempat formula, didapatkan bahwa sifat listrik yang paling baik terdapat pada formula empat dengan penambahan grafit sebesar 40 wt%. Formulasi empat memiliki konduktivitas listrik sebesar 2,523E-03 S/cm. sifat listrik juga belum optimal dikarenakan masih terdapatnya banyak rongga atau pori dalam komposit PP/grafit/CB yang disebabkan oleh udara yang terjebak selama proses penekanan.

Electroplating of Ni-Mo Coating on Stainless Steel for Application in Proton Exchange Membrane Fuel Cell Bipolar Plate

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H. Rashtchi

2018-03-01

Full Text Available Stainless steel bipolar plates are preferred choice for use in Proton Exchange Membrane Fuel Cells (PEMFCs. However, regarding the working temperature of 80 °C and corrosive and acidic environment of PEMFC, it is necessary to apply conductive protective coatings resistant to corrosion on metallic bipolar plate surfaces to enhance its chemical stability and performance. In the present study, by applying Ni-Mo and Ni-Mo-P alloy coatings via electroplating technique, corrosion resistance was improved, oxid layers formation on substrates which led to increased electrical conductivity of the surface was reduced and consequently bipolar plates fuction was enhanced. Evaluation tests included microstructural and phase characterizations for evaluating coating components; cyclic voltammetry test for electrochemical behavior investigations; wettability test for measuring hydrophobicity characterizations of the coatings surfaces; interfacial contact resistance measurements of the coatings for evaluating the composition of applied coatings; and polarization tests of fuel cells for evaluating bipolar plates function in working conditions. Finally, the results showed that the above-mentioned coatings considerably decreased the corrosion and electrical resistance of the stainless steel.

Bipolar Disorder and Cancer

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Sermin Kesebir

2012-06-01

Full Text Available Prevalence studies and studies on causation relations have shown that the relation between psychiatric disorders and chronic physical diseases is neglected. For heterogeneous diseases an increasing number of susceptibility variants are being defined. Alzheimer disease, bipolar disorder, breast and prostate cancer, coronary artery disease, Chron's disease, systemic lupus eritematosus, type 1 and type 2 diabetes mellitus are mentioned together with epigenetic concept. In acrocentric zone of chromosome 13, breast cancer, retinoblastoma, chronic Iymphocytic leukemia genes with B cells, dopamin loci of bipolar disorder are found together. Among bipolar and healthy individuals, an increase risk of breast cancer in female cases has been resported. On the other hand, psychosocial factors that affect stress and response to stress itself may be important variables in prognosis and progression of different cancer types. During the course of many cancer types –especially brain tumors- and during treatment of chemotherapeutic agents, bipolar symptomatology may appear. In this article, it is reviewed with relevant literature that whether an etiological relation between bipolar disorder and cancer exist and how both diseases affect each other's course and treatment.

Current density and catalyst-coated membrane resistance distribution of hydro-formed metallic bipolar plate fuel cell short stack with 250 cm2 active area

Science.gov (United States)

Haase, S.; Moser, M.; Hirschfeld, J. A.; Jozwiak, K.

2016-01-01

An automotive fuel cell with an active area of 250 cm2 is investigated in a 4-cell short stack with a current and temperature distribution device next to the bipolar plate with 560 current and 140 temperature segments. The electrical conductivities of the bipolar plate and gas diffusion layer assembly are determined ex-situ with this current scan shunt module. The applied fuel cell consists of bipolar plates constructed of 75-μm-thick, welded stainless-steel foils and a graphitic coating. The electrical conductivities of the bipolar plate and gas diffusion layer assembly are determined ex-situ with this module with a 6% deviation in in-plane conductivity. The current density distribution is evaluated up to 2.4 A cm-2. The entire cell's investigated volumetric power density is 4.7 kW l-1, and its gravimetric power density is 4.3 kW kg-1 at an average cell voltage of 0.5 V. The current density distribution is determined without influencing the operating cell. In addition, the current density distribution in the catalyst-coated membrane and its effective resistivity distribution with a finite volume discretisation of Ohm's law are evaluated. The deviation between the current density distributions in the catalyst-coated membrane and the bipolar plate is determined.

Lamotrigine blocks NMDA receptor-initiated arachidonic acid signalling in rat brain: Implications for its efficacy in bipolar disorder

Science.gov (United States)

Ramadan, Epolia; Basselin, Mireille; Rao, Jagadeesh S.; Chang, Lisa; Chen, Mei; Ma, Kaizong; Rapoport, Stanley I.

2011-01-01

An upregulated brain arachidonic acid (AA) cascade and a hyperglutamatergic state characterize bipolar disorder (BD). Lamotrigine (LTG), a mood stabilizer approved for treating BD, is reported to interfere with glutamatergic neurotransmission involving N-methyl-D-aspartate receptors (NMDARs). NMDARs allow extracellular calcium into the cell, thereby stimulating calcium-dependent cytosolic phospholipase A2 (cPLA2) to release arachidonic acid (AA) from membrane phospholipid. We hypothesized that LTG, like other approved mood stabilizers, would reduce NMDAR-mediated AA signaling in rat brain. An acute subconvulsant dose of NMDA (25 mg/kg) or saline was administered intraperitoneally to unanesthetized rats that had been treated p.o. daily for 42 days with vehicle or a therapeutically relevant dose of LTG (10 mg/kg/.d). Regional brain AA incorporation coefficients k* and rates Jin, AA signals, were measured using quantitative autoradiography after intravenous [1-14C]AA infusion, as were other AA cascade markers. In chronic vehicle-treated rats, acute NMDA compared to saline increased k* and Jin in widespread regions of the brain, as well as prostaglandin (PG)E2 and thromboxane B2 concentrations. Chronic LTG treatment compared to vehicle reduced brain cyclooxygenase (COX) activity, PGE2 concentration, and DNA binding activity of the COX-2 transcription factor, NF-κB. Pretreatment with chronic LTG blocked the acute NMDA effects on AA cascade markers. In summary, chronic LTG like other mood stabilizers blocks NMDA-mediated signaling involving the AA metabolic cascade. Since markers of the AA cascade and of NMDAR signaling are up-regulated in the postmortem BD brain, mood stabilizers generally may be effective in BD by dampening NMDAR signalling and the AA cascade. PMID:21733229

Beyond the therapeutic shackles of the monoamines: New mechanisms in bipolar disorder biology.

Science.gov (United States)

Data-Franco, João; Singh, Ajeet; Popovic, Dina; Ashton, Melanie; Berk, Michael; Vieta, Eduard; Figueira, M L; Dean, Olivia M

2017-01-04

Multiple novel biological mechanisms putatively involved in the etiology of bipolar disorders are being explored. These include oxidative stress, altered glutamatergic neurotransmission, mitochondrial dysfunction, inflammation, cell signaling, apoptosis and impaired neurogenesis. Important clinical translational potential exists for such mechanisms to help underpin development of novel therapeutics - much needed given limitations of current therapies. These new mechanisms also help improve our understanding of how current therapeutics might exert their effects. Lithium, for example, appears to have antioxidant, immunomodulatory, signaling, anti-apoptotic and neuroprotective properties. Similar properties have been attributed to other mood stabilizers such as valproate, lamotrigine, and quetiapine. Perhaps of greatest translational value has been the recognition of such mechanisms leading to the emergence of novel therapeutics for bipolar disorders. These include the antioxidant N-acetylcysteine, the anti-inflammatory celecoxib, and ketamine - with effects on the glutamatergic system and microglial inhibition. We review these novel mechanisms and emerging therapeutics, and comment on next steps in this space. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparative familial aggregation of bipolar disorder in patients with bipolar I and bipolar II disorders.

Science.gov (United States)

Parker, Gordon B; Romano, Mia; Graham, Rebecca K; Ricciardi, Tahlia

2018-05-01

We sought to quantify the prevalence and differential prevalence of a bipolar disorder among family members of patients with a bipolar I or II disorder. The sample comprised 1165 bipolar and 1041 unipolar patients, with the former then sub-typed as having either a bipolar I or II condition. Family history data was obtained via an online self-report tool. Prevalence of a family member having a bipolar disorder (of either sub-type) was distinctive (36.8%). Patients with a bipolar I disorder reported a slightly higher family history (41.2%) compared to patients with a bipolar II disorder (36.3%), and with both significantly higher than the rate of bipolar disorder in family members of unipolar depressed patients (18.5%). Findings support the view that bipolar disorder is heritable. The comparable rates in the two bipolar sub-types support the positioning of bipolar II disorder as a valid condition with strong genetic underpinnings.

Bipolar zinc/oxygen battery development

Energy Technology Data Exchange (ETDEWEB)

Mueller, S [Paul Scherrer Inst. (PSI), Villigen (Switzerland); Schlatter, C [Swiss Federal Inst. of Technology, Lausanne (Switzerland)

1997-06-01

A bipolar electrically rechargeable Zn/O{sub 2} battery has been developed. Reticulated copper foam served as substrate for the zinc deposit on the anodic side, and La{sub 0.6}Ca{sub 0.4}CoO{sub 3}-catalyzed bifunctional oxygen electrodes were used on the cathodic side of the cells. The 100 cm{sup 2} unit cell had an open circuit voltage of 1,4 V(O{sub 2}) in moderately alkaline electrolyte. The open circuit voltage and the peak power measured for a stack containing seven cells were ca. 10V and 90W, respectively. The current-potential behaviour was determined as a function of the number of bipolar cells, and the maximum discharge capacity was determined at different discharge rates. (author) 4 figs., 1 ref.

An investigation of coated aluminium bipolar plates for PEMFC

International Nuclear Information System (INIS)

Lin, Chien-Hung; Tsai, Sung-Ying

2012-01-01

Highlights: ► Coated aluminium bipolar plates demonstrate the hydrophobic property than the raw material. ► The corrosion behaviour of bipolar plate decreases the PEMFC performance severely. ► These PEMFCs are measured by current–voltage (I–V) curve test. ► The oxide film increases the interfacial contact resistance. -- Abstract: The performance of Al-alloy bipolar plates for the PEMFC (proton exchange membrane fuel cell) system is investigated in this paper. The metallic bipolar plates are modified with a Ni–P coating. The performance of the Al-alloy bipolar plates is evaluated by the coating structure, corrosion resistance, contact angle and single cell performance. The results indicate that the coated aluminium bipolar plates demonstrate hydrophobic and anti-corrosive properties. The hydrophobic property increases the contact angle on the surface from 46.08° to 80.51°. Meanwhile, the corrosion rate of the Ni–P coating can be over 1 order of magnitude lower than that of the substrate. Hence, the substrate with the coating maintains superior performance under the long term test. The present study proves that both the hydrophobicity and corrosion resistance significantly affect the metallic bipolar plate.

Anticorrosion Coating of Carbon Nanotube/Polytetrafluoroethylene Composite Film on the Stainless Steel Bipolar Plate for Proton Exchange Membrane Fuel Cells

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Yoshiyuki Show

2013-01-01

Full Text Available Composite film of carbon nanotube (CNT and polytetrafluoroethylene (PTFE was formed from dispersion fluids of CNT and PTFE. The composite film showed high electrical conductivity in the range of 0.1–13 S/cm and hydrophobic nature. This composite film was applied to stainless steel (SS bipolar plates of the proton exchange membrane fuel cell (PEMFC as anticorrosion film. This coating decreased the contact resistance between the surface of the bipolar plate and the membrane electrode assembly (MEA of the PEMFC. The output power of the fuel cell is increased by 1.6 times because the decrease in the contact resistance decreases the series resistance of the PEMFC. Moreover, the coating of this composite film protects the bipolar plate from the surface corrosion.

High-pass filtering of input signals by the Ih current in a non-spiking neuron, the retinal rod bipolar cell.

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Lorenzo Cangiano

Full Text Available Hyperpolarization-activated cyclic nucleotide-sensitive (HCN channels mediate the I(f current in heart and I(h throughout the nervous system. In spiking neurons I(h participates primarily in different forms of rhythmic activity. Little is known, however, about its role in neurons operating with graded potentials as in the retina, where all four channel isoforms are expressed. Intriguing evidence for an involvement of I(h in early visual processing are the side effects reported, in dim light or darkness, by cardiac patients treated with HCN inhibitors. Moreover, electroretinographic recordings indicate that these drugs affect temporal processing in the outer retina. Here we analyzed the functional role of HCN channels in rod bipolar cells (RBCs of the mouse. Perforated-patch recordings in the dark-adapted slice found that RBCs exhibit I(h, and that this is sensitive to the specific blocker ZD7288. RBC input impedance, explored by sinusoidal frequency-modulated current stimuli (0.1-30 Hz, displays band-pass behavior in the range of I(h activation. Theoretical modeling and pharmacological blockade demonstrate that high-pass filtering of input signals by I(h, in combination with low-pass filtering by passive properties, fully accounts for this frequency-tuning. Correcting for the depolarization introduced by shunting through the pipette-membrane seal, leads to predict that in darkness I(h is tonically active in RBCs and quickens their responses to dim light stimuli. Immunohistochemistry targeting candidate subunit isoforms HCN1-2, in combination with markers of RBCs (PKC and rod-RBC synaptic contacts (bassoon, mGluR6, Kv1.3, suggests that RBCs express HCN2 on the tip of their dendrites. The functional properties conferred by I(h onto RBCs may contribute to shape the retina's light response and explain the visual side effects of HCN inhibitors.

Nickel hydrogen bipolar battery electrode design

Science.gov (United States)

Puglisi, V. J.; Russell, P.; Verrier, D.; Hall, A.

1985-01-01

The preferred approach of the NASA development effort in nickel hydrogen battery design utilizes a bipolar plate stacking arrangement to obtain the required voltage-capacity configuration. In a bipolar stack, component designs must take into account not only the typical design considerations such as voltage, capacity and gas management, but also conductivity to the bipolar (i.e., intercell) plate. The nickel and hydrogen electrode development specifically relevant to bipolar cell operation is discussed. Nickel oxide electrodes, having variable type grids and in thicknesses up to .085 inch are being fabricated and characterized to provide a data base. A selection will be made based upon a system level tradeoff. Negative (hydrpogen) electrodes are being screened to select a high performance electrode which can function as a bipolar electrode. Present nickel hydrogen negative electrodes are not capable of conducting current through their cross-section. An electrode was tested which exhibits low charge and discharge polarization voltages and at the same time is conductive. Test data is presented.

Bipolar Treatment: Are Bipolar I and Bipolar II Treated Differently?

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... The diagnosis and management of bipolar I and bipolar II disorders: Clinical practice update. Mayo Clinic Proceedings. 2017;92:1532. Haynes PL, et al. Social rhythm therapies for mood disorders: An update. Current Psychiatry Reports. ...

Theoretical design strategies of bipolar membrane fuel cell with enhanced self-humidification behavior

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Li, Qiushi; Gong, Jian; Peng, Sikan; Lu, Shanfu; Sui, Pang-Chieh; Djilali, Ned; Xiang, Yan

2016-03-01

The bipolar membrane fuel cells (BPMFCs), which have a unique acid-alkaline jointed membrane electrode assembly (MEA) structure, have demonstrated their great potential for self-humidification during operation. Although the self-humidification ability of such bipolar membranes (BPMs) has recently been validated by a one-dimensional BPM model, the transport mechanism and the formation of self-humidification in the MEAs are not well understood. In the present study, a two-dimensional cross-channel MEA model is developed to elucidate the mechanisms and enhancement of water transport on self-humidification with comprehensive consideration of the three electrochemical reaction zones. The water-formation interface model has been successfully investigated by theoretical and experimental interface reaction kinetics, streamlines of water flux present the formation process and mechanism of self-humidification. A critical current (voltage) value, beyond which self-humidification is initiated, is identified. It is also found that such critical current (voltage) can be adjusted by changing the membrane thickness and the water uptake property of the ionomer. It is concluded that fabricating BPMs with proper membrane thickness and water uptake property are effective strategies to enhance the water management and cell performance in BPMFCs.

Lrit1, a Retinal Transmembrane Protein, Regulates Selective Synapse Formation in Cone Photoreceptor Cells and Visual Acuity

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Akiko Ueno

2018-03-01

Full Text Available Summary: In the vertebrate retina, cone photoreceptors play crucial roles in photopic vision by transmitting light-evoked signals to ON- and/or OFF-bipolar cells. However, the mechanisms underlying selective synapse formation in the cone photoreceptor pathway remain poorly understood. Here, we found that Lrit1, a leucine-rich transmembrane protein, localizes to the photoreceptor synaptic terminal and regulates the synaptic connection between cone photoreceptors and cone ON-bipolar cells. Lrit1-deficient retinas exhibit an aberrant morphology of cone photoreceptor pedicles, as well as an impairment of signal transmission from cone photoreceptors to cone ON-bipolar cells. Furthermore, we demonstrated that Lrit1 interacts with Frmpd2, a photoreceptor scaffold protein, and with mGluR6, an ON-bipolar cell-specific glutamate receptor. Additionally, Lrit1-null mice showed visual acuity impairments in their optokinetic responses. These results suggest that the Frmpd2-Lrit1-mGluR6 axis regulates selective synapse formation in cone photoreceptors and is essential for normal visual function. : Ueno et al. finds that Lrit1 plays an important role in regulating the synaptic connection between cone photoreceptors and cone ON-bipolar cells. The Frmpd2-Lrit1-mGluR6 axis is crucial for selective synapse formation in cone photoreceptors and for development of normal visual function. Keywords: retina, circuit, synapse formation, cone photoreceptor cell, ON-bipolar cell, visual acuity

Homer1a protein expression in schizophrenia, bipolar disorder, and major depression.

Science.gov (United States)

Leber, Stefan L; Llenos, Ida C; Miller, Christine L; Dulay, Jeannette R; Haybaeck, Johannes; Weis, Serge

2017-10-01

In recent years, there was growing interest in postsynaptic density proteins in the central nervous system. Of the most important candidates of this specialized region are proteins belonging to the Homer protein family. This family of scaffolding proteins is suspected to participate in the pathogenesis of a variety of diseases. The present study aims to compare Homer1a expression in the hippocampus and cingulate gyrus of patients with major psychiatric disorders including schizophrenia, bipolar disorder and major depression. Immunohistochemistry was used to analyze changes of Homer1a protein expression in the hippocampal formation and the cingulate gyrus from the respective disease groups. Glial cells of the cingulate gyrus gray matter showed decreased Homer1a levels in bipolar disorder when compared to controls. The same results were seen when comparing cingulate gyrus gray matter glial cells in bipolar disorder with major depression. Stratum oriens glial cells of the hippocampus showed decreased Homer1a levels in bipolar disorder when compared to controls and major depression. Stratum lacunosum glial cells showed decreased Homer1a levels in bipolar disorder when compared to major depression. In stratum oriens interneurons Homer1a levels were increased in all disease groups when compared to controls. Stratum lucidum axons showed decreased Homer1a levels in bipolar disorder when compared to controls. Our data demonstrate altered Homer1a levels in specific brain regions and cell types of patients suffering from schizophrenia, bipolar disorder and major depression. These findings support the role of Homer proteins as interesting candidates in neuropsychiatric pathophysiology and treatment.

PEM fuel cells with injection moulded bipolar plates of highly filled graphite compounds; PEM-Brennstoffzellen mit spritzgegossenen Bipolarplatten aus hochgefuelltem Graphit-Compound

Energy Technology Data Exchange (ETDEWEB)

Kreuz, Can

2008-04-11

This work concerns with the injection moulding of highly filled graphite compounds to bipolar plates for PEM fuel cells in a power output range between 100 - 500 Watts. A particular focus is laid on the combination of the three multidisciplinary scopes like material development, production technology and component development / design. The results of the work are specified by the process-oriented characterisation of the developed and manufactured bipolar plates as well as their application in a functioning fuel cell. (orig.)

PEMFC Performance with Metal Bipolar Plates Depending on the Channel Dimension

Directory of Open Access Journals (Sweden)

Kwon Kuikam

2016-01-01

Full Text Available Bipolar plates of a proton exchange membrane fuel cell (PEMFC play an important role in removing liquid phase water as a by-product in order to facilitate the reaction between fuel and oxygen. A great amount of effort has been made to improve the performance of a fuel cell such as maximum current density or maximum power, by improving water removability of a bipolar plate. Most of the studies, however, are conducted numerically because of the complexity of analysing gas and liquid and the poor manufacturability of graphite bipolar plates. In this proceeding, we demonstrate that the performance of a PEMFC with metal bipolar plates can be enhanced by reducing the dimension of the channel. Bipolar plates were machined with stainless steel (type 316L to have three different channel size (1000 μm, 500 μm and 300 μm and the performance of each assembled cells were tested. As a result, the maximum power density and the maximum current density increased by 25%.

A missense mutation in Grm6 reduces but does not eliminate mGluR6 expression or rod depolarizing bipolar cell function.

Science.gov (United States)

Peachey, Neal S; Hasan, Nazarul; FitzMaurice, Bernard; Burrill, Samantha; Pangeni, Gobinda; Karst, Son Yong; Reinholdt, Laura; Berry, Melissa L; Strobel, Marge; Gregg, Ronald G; McCall, Maureen A; Chang, Bo

2017-08-01

GRM6 encodes the metabotropic glutamate receptor 6 (mGluR6) used by retinal depolarizing bipolar cells (DBCs). Mutations in GRM6 lead to DBC dysfunction and underlie the human condition autosomal recessive complete congenital stationary night blindness. Mouse mutants for Grm6 are important models for this condition. Here we report a new Grm6 mutant, identified in an electroretinogram (ERG) screen of mice maintained at The Jackson Laboratory. The Grm6 nob8 mouse has a reduced-amplitude b-wave component of the ERG, which reflects light-evoked DBC activity. Sequencing identified a missense mutation that converts a highly conserved methionine within the ligand binding domain to leucine (p.Met66Leu). Consistent with prior studies of Grm6 mutant mice, the laminar size and structure in the Grm6 nob8 retina were comparable to control. The Grm6 nob8 phenotype is distinguished from other Grm6 mutants that carry a null allele by a reduced but not absent ERG b-wave, decreased but present expression of mGluR6 at DBC dendritic tips, and mislocalization of mGluR6 to DBC somas. Consistent with a reduced but not absent b-wave, there were a subset of retinal ganglion cells whose responses to light onset have times to peak within the range of those in control retinas. These data indicate that the p.Met66Leu mutant mGluR6 is trafficked less than control. However, the mGluR6 that is localized to the DBC dendritic tips is able to initiate DBC signal transduction. The Grm6 nob8 mouse extends the Grm6 allelic series and will be useful for elucidating the role of mGluR6 in DBC signal transduction and in human disease. NEW & NOTEWORTHY This article describes a mouse model of the human disease complete congenital stationary night blindness in which the mutation reduces but does not eliminate GRM6 expression and bipolar cell function, a distinct phenotype from that seen in other Grm6 mouse models.

Ag-polytetrafluoroethylene composite coating on stainless steel as bipolar plate of proton exchange membrane fuel cell

Energy Technology Data Exchange (ETDEWEB)

Fu, Yu. [Laboratory of Fuel Cells, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Zhongshan Road, Dalian 116023 (China); Graduate University of Chinese Academy of Sciences, Beijing 100049 (China); Hou, Ming; Shao, Zhigang; Yi, Baolian [Laboratory of Fuel Cells, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Zhongshan Road, Dalian 116023 (China); Xu, Hongfeng; Hou, Zhongjun; Ming, Pingwen [Sunrise Power Co., Ltd., Dalian 116025 (China)

2008-08-01

Forming a coating on metals by surface treatment is a good way to get high performance bipolar plate of proton exchange membrane fuel cell (PEMFC). In our research, Ag-polytetrafluoroethylene (PTFE) composite film was electrodeposited with silver-gilt solution of nicotinic acid by a bi-pulse electroplating power supply on 316 L stainless steel bipolar plate of PEMFC. Surface topography, contact angle, interfacial conductivity and corrosion resistance of the bipolar plate samples were investigated. Results showed that the defects on the Ag-PTFE composite coating are greatly reduced compared with those on the pure Ag coating fabricated under the same condition; and the contact angle of the Ag-PTFE composite coating with water is 114 , which is much bigger than that of the pure Ag coating (73 ). In addition, the interfacial contact resistance of the composite coating stays as low as the pure Ag coating; and the bipolar plate sample with composite coating shows a close corrosion resistance to the pure Ag coating sample in potentiodynamic and potentiostatic tests. Coated 316 L stainless steel plate with Ag-PTFE composite coating exhibits well hydrophobic characteristic, less defects, high interfacial conductivity and good corrosion resistance, which shows a great potential of the application in PEMFC. (author)

Lrit1, a Retinal Transmembrane Protein, Regulates Selective Synapse Formation in Cone Photoreceptor Cells and Visual Acuity.

Science.gov (United States)

Ueno, Akiko; Omori, Yoshihiro; Sugita, Yuko; Watanabe, Satoshi; Chaya, Taro; Kozuka, Takashi; Kon, Tetsuo; Yoshida, Satoyo; Matsushita, Kenji; Kuwahara, Ryusuke; Kajimura, Naoko; Okada, Yasushi; Furukawa, Takahisa

2018-03-27

In the vertebrate retina, cone photoreceptors play crucial roles in photopic vision by transmitting light-evoked signals to ON- and/or OFF-bipolar cells. However, the mechanisms underlying selective synapse formation in the cone photoreceptor pathway remain poorly understood. Here, we found that Lrit1, a leucine-rich transmembrane protein, localizes to the photoreceptor synaptic terminal and regulates the synaptic connection between cone photoreceptors and cone ON-bipolar cells. Lrit1-deficient retinas exhibit an aberrant morphology of cone photoreceptor pedicles, as well as an impairment of signal transmission from cone photoreceptors to cone ON-bipolar cells. Furthermore, we demonstrated that Lrit1 interacts with Frmpd2, a photoreceptor scaffold protein, and with mGluR6, an ON-bipolar cell-specific glutamate receptor. Additionally, Lrit1-null mice showed visual acuity impairments in their optokinetic responses. These results suggest that the Frmpd2-Lrit1-mGluR6 axis regulates selective synapse formation in cone photoreceptors and is essential for normal visual function. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

A combined analysis of genome-wide expression profiling of bipolar disorder in human prefrontal cortex.

Science.gov (United States)

Wang, Jinglu; Qu, Susu; Wang, Weixiao; Guo, Liyuan; Zhang, Kunlin; Chang, Suhua; Wang, Jing

2016-11-01

Numbers of gene expression profiling studies of bipolar disorder have been published. Besides different array chips and tissues, variety of the data processes in different cohorts aggravated the inconsistency of results of these genome-wide gene expression profiling studies. By searching the gene expression databases, we obtained six data sets for prefrontal cortex (PFC) of bipolar disorder with raw data and combinable platforms. We used standardized pre-processing and quality control procedures to analyze each data set separately and then combined them into a large gene expression matrix with 101 bipolar disorder subjects and 106 controls. A standard linear mixed-effects model was used to calculate the differentially expressed genes (DEGs). Multiple levels of sensitivity analyses and cross validation with genetic data were conducted. Functional and network analyses were carried out on basis of the DEGs. In the result, we identified 198 unique differentially expressed genes in the PFC of bipolar disorder and control. Among them, 115 DEGs were robust to at least three leave-one-out tests or different pre-processing methods; 51 DEGs were validated with genetic association signals. Pathway enrichment analysis showed these DEGs were related with regulation of neurological system, cell death and apoptosis, and several basic binding processes. Protein-protein interaction network further identified one key hub gene. We have contributed the most comprehensive integrated analysis of bipolar disorder expression profiling studies in PFC to date. The DEGs, especially those with multiple validations, may denote a common signature of bipolar disorder and contribute to the pathogenesis of disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

Aberrant cerebellar connectivity in bipolar disorder with psychosis.

Science.gov (United States)

Shinn, Ann K; Roh, Youkyung S; Ravichandran, Caitlin T; Baker, Justin T; Öngür, Dost; Cohen, Bruce M

2017-07-01

The cerebellum, which modulates affect and cognition in addition to motor functions, may contribute substantially to the pathophysiology of mood and psychotic disorders, such as bipolar disorder. A growing literature points to cerebellar abnormalities in bipolar disorder. However, no studies have investigated the topographic representations of resting state cerebellar networks in bipolar disorder, specifically their functional connectivity to cerebral cortical networks. Using a well-defined cerebral cortical parcellation scheme as functional connectivity seeds, we compared ten cerebellar resting state networks in 49 patients with bipolar disorder and a lifetime history of psychotic features and 55 healthy control participants matched for age, sex, and image signal-to-noise ratio. Patients with psychotic bipolar disorder showed reduced cerebro-cerebellar functional connectivity in somatomotor A, ventral attention, salience, and frontoparietal control A and B networks relative to healthy control participants. These findings were not significantly correlated with current symptoms. Patients with psychotic bipolar disorder showed evidence of cerebro-cerebellar dysconnectivity in selective networks. These disease-related changes were substantial and not explained by medication exposure or substance use. Therefore, they may be mechanistically relevant to the underlying susceptibility to mood dysregulation and psychosis. Cerebellar mechanisms deserve further exploration in psychiatric conditions, and this study's findings may have value in guiding future studies on pathophysiology and treatment of mood and psychotic disorders, in particular.

Is bipolar always bipolar? Understanding the controversy on bipolar disorder in children

Science.gov (United States)

Grimmer, Yvonne; Hohmann, Sarah

2014-01-01

Dramatically increasing prevalence rates of bipolar disorder in children and adolescents in the United States have provoked controversy regarding the boundaries of manic symptoms in child and adolescent psychiatry. The serious impact of this ongoing debate on the treatment of affected children is reflected in the concomitant increase in prescription rates for antipsychotic medication. A key question in the debate is whether this increase in bipolar disorder in children and adolescents is based on a better detection of early-onset bipolar disorder—which can present differently in children and adolescents—or whether it is caused by an incorrect assignment of symptoms which overlap with other widely known disorders. So far, most findings suggest that the suspected symptoms, in particular chronic, non-episodic irritability (a mood symptom presenting with easy annoyance, temper tantrums and anger) do not constitute a developmental presentation of childhood bipolar disorder. Additional research based on prospective, longitudinal studies is needed to further clarify the developmental trajectories of bipolar disorder and the diagnostic status of chronic, non-episodic irritability. PMID:25580265

Efficient treatment of aniline containing wastewater in bipolar membrane microbial electrolysis cell-Fenton system.

Science.gov (United States)

Li, Xiaohu; Jin, Xiangdan; Zhao, Nannan; Angelidaki, Irini; Zhang, Yifeng

2017-08-01

Aniline-containing wastewater can cause significant environmental problems and threaten the humans's life. However, rapid degradation of aniline with cost-efficient methods remains a challenge. In this work, a novel microbial electrolysis cell with bipolar membrane was integrated with Fenton reaction (MEC-Fenton) for efficient treatment of real wastewater containing a high concentration (4460 ± 52 mg L -1 ) of aniline. In this system, H 2 O 2 was in situ electro-synthesized from O 2 reduction on the graphite cathode and was simultaneously used as source of OH for the oxidation of aniline wastewater under an acidic condition maintained by the bipolar membrane. The aniline was effectively degraded following first-order kinetics at a rate constant of 0.0166 h -1 under an applied voltage of 0.5 V. Meanwhile, a total organic carbon (TOC) removal efficiency of 93.1 ± 1.2% was obtained, revealing efficient mineralization of aniline. The applicability of bipolar membrane MEC-Fenton system was successfully demonstrated with actual aniline wastewater. Moreover, energy balance showed that the system could be a promising technology for removal of biorefractory organic pollutants from wastewaters. Copyright © 2017 Elsevier Ltd. All rights reserved.

[A case of Neuro-Behçet's disease with early onset of bipolar mood disorder].

Science.gov (United States)

Nakano, Yuko; Hatanaka, Yuki; Ikebuchi, Emi; Shimizu, Teruo; Nanko, Shinichiro; Utsumii, Takeshi

2004-01-01

In this report, we describe a case of Neuro-Behçet's disease with early onset of bipolar mood disorder. A 53-year-old man with neuropathy including dysphasia and dyslalia developed bipolar mood disorder with anxiety, agitation, depressive mood, talkativeness, hyperkinesias, and appetite rise, and soon exhibited severe personality deterioration. Oral aphthae, cell proliferation and elevated IL-6 levels in spinal fluid, and the patient's clinical downhill course with remission and relapse in spite of good reaction to steroid preparation indicated the possibility of Neuro-Behçet's disease. Brain MRI showed clear swelling of the brain stem area, especially in the pons, in the active phase with low signal in T1-weighted images contrasting with clear high signal in T2-weighted images and FLAIR. At the time of remission, atrophy of the brain stem was shown. These findings were consistent with the view reported in recent years concerning the brain image of Neuro-Behçet's disease, which seemed to be useful for the differential diagnosis. This case manifested two outstanding clinical features. First, it showed bipolar mood swing or mixed state distinguishable from disinhibition or euphoria in deteriorated personality, which is common in this condition. A clear bipolar mood disorder has not been described until now in Neuro-Behçet's disease. Second, subclinical dysthymia or hypomanic phase occurred before clear onset of the disease. In Neuro-Behçet's disease, it is currently considered that psychiatric symptoms may appear in the early stage, but there is controversy as to whether they can precede the other symptoms. Our case indicated very early onset of psychiatric symptoms in this condition.

Tritium isotope separation from light and heavy water by bipolar electrolysis

International Nuclear Information System (INIS)

Petek, M.; Ramey, D.W.; Taylor, R.D.; Kobisk, E.H.

1980-01-01

A process for separating tritium from light and heavy water is described. Hydrogen is transferred at and through bipolar electrodes at rates H > D > T. In a cell containing several bipolar electrodes placed in series between two terminal electrodes, a flow of hydrogen is established from the terminal anode compartment toward the terminal cathode. An electrolyte feed containing tritium is continuously added to the system and is subsequently transported countercurrent to the hydrogen mass transfer. A cascaded system is established, in which effluent streams enriched and depleted in tritium can be withdrawn. The voltage drop is smaller at any bipolar electrode as compared to the voltage for normal electrolysis. Cell design is compact because isotope separation occurs at bipolar electrodes without evolution of gas. Isotope separation was demonstrated in laboratory cells where a steady-state tritium concentration gradient was attained. This gradient was in agreement with concentrations calculated from a derived mathematical model

The second phase of bipolar, nanosecond-range electric pulses determines the electroporation efficiency.

Science.gov (United States)

Pakhomov, Andrei G; Grigoryev, Sergey; Semenov, Iurii; Casciola, Maura; Jiang, Chunqi; Xiao, Shu

2018-03-29

Bipolar cancellation refers to a phenomenon when applying a second electric pulse reduces ("cancels") cell membrane damage by a preceding electric pulse of the opposite polarity. Bipolar cancellation is a reason why bipolar nanosecond electric pulses (nsEP) cause weaker electroporation than just a single unipolar phase of the same pulse. This study was undertaken to explore the dependence of bipolar cancellation on nsEP parameters, with emphasis on the amplitude ratio of two opposite polarity phases of a bipolar pulse. Individual cells (CHO, U937, or adult mouse ventricular cardiomyocytes (VCM)) were exposed to either uni- or bipolar trapezoidal nsEP, or to nanosecond electric field oscillations (NEFO). The membrane injury was evaluated by time-lapse confocal imaging of the uptake of propidium (Pr) or YO-PRO-1 (YP) dyes and by phosphatidylserine (PS) externalization. Within studied limits, bipolar cancellation showed little or no dependence on the electric field intensity, pulse repetition rate, chosen endpoint, or cell type. However, cancellation could increase for larger pulse numbers and/or for longer pulses. The sole most critical parameter which determines bipolar cancellation was the phase ratio: maximum cancellation was observed with the 2nd phase of about 50% of the first one, whereas a larger 2nd phase could add a damaging effect of its own. "Swapping" the two phases, i.e., delivering the smaller phase before the larger one, reduced or eliminated cancellation. These findings are discussed in the context of hypothetical mechanisms of bipolar cancellation and electroporation by nsEP. Copyright © 2018 Elsevier B.V. All rights reserved.

Bipolar plate materials in molten carbonate fuel cells. Final CRADA report.

Energy Technology Data Exchange (ETDEWEB)

Krumpelt, M.

2004-06-01

Advantages of implementation of power plants based on electrochemical reactions are successfully demonstrated in the USA and Japan. One of the msot promising types of fuel cells (FC) is a type of high temperature fuel cells. At present, thanks to the efforts of the leading countries that develop fuel cell technologies power plants on the basis of molten carbonate fuel cells (MCFC) and solid oxide fuel cells (SOFC) are really close to commercialization. One of the problems that are to be solved for practical implementation of MCFC and SOFC is a problem of corrosion of metal components of stacks that are assembled of a number of fuel cells. One of the major components of MCFC and SOFC stacks is a bipolar separator plate (BSP) that performs several functions - it is separation of reactant gas flows sealing of the joints between fuel cells, and current collection from the surface of electrodes. The goal of Task 1 of the project is to develop new cost-effective nickel coatings for the Russian 20X23H18 steel for an MCFC bipolar separator plate using technological processes usually implemented to apply corrosion stable coatings onto the metal parts for products in the defense. There was planned the research on production of nickel coatings using different methods, first of all the galvanic one and the explosion cladding one. As a result of the works, 0.4 x 712 x 1296 mm plates coated with nickel on one side were to be made and passed to ANL. A line of 4 galvanic baths 600 liters was to be built for the galvanic coating applications. The goal of Task 2 of the project is the development of a new material of an MCFC bipolar separator plate with an upgraded corrosion stability, and development of a technology to produce cold roll sheets of this material the sizes of which will be 0.8 x 712x 1296 mm. As a result of these works, a pilot batch of the rolled material in sheets 0.8 x 712 x 1296 mm in size is to be made (in accordance with the norms and standards of the Russian

Technical Note: Interleaved Bipolar Acquisition and Low-rank Reconstruction for Water-Fat Separation in MRI.

Science.gov (United States)

Cho, JaeJin; Park, HyunWook

2018-05-17

To acquire interleaved bipolar data and reconstruct the full data using low-rank property for water fat separation. Bipolar acquisition suffers from issues related to gradient switching, the opposite gradient polarities, and other system imperfections, which prevent accurate water-fat separation. In this study, an interleaved bipolar acquisition scheme and a low-rank reconstruction method were proposed to reduce issues from the bipolar gradients while achieving a short imaging time. The proposed interleaved bipolar acquisition scheme collects echo-time signals from both gradient polarities; however, the sequence increases the imaging time. To reduce the imaging time, the signals were subsampled at every dimension of k-space. The low-rank property of the bipolar acquisition was defined and exploited to estimate the full data from the acquired subsampled data. To eliminate the bipolar issues, in the proposed method, the water-fat separation was performed separately for each gradient polarity, and the results for the positive and negative gradient polarities were combined after the water-fat separation. A phantom study and in-vivo experiments were conducted on a 3T Siemens Verio system. The results for the proposed method were compared with the results of the fully sampled interleaved bipolar acquisition and Soliman's method, which was the previous water-fat separation approach for reducing the issues of bipolar gradients and accelerating the interleaved bipolar acquisition. The proposed method provided accurate water and fat images without the issues of bipolar gradients and demonstrated a better performance compared with the results of the previous methods. The water-fat separation using the bipolar acquisition has several benefits including a short echo-spacing time. However, it suffers from bipolar-gradient issues such as strong gradient switching, system imperfection, and eddy current effects. This study demonstrated that accurate water-fat separated images can

Nanosecond bipolar pulse generators for bioelectrics.

Science.gov (United States)

Xiao, Shu; Zhou, Chunrong; Yang, Enbo; Rajulapati, Sambasiva R

2018-04-26

Biological effects caused by a nanosecond pulse, such as cell membrane permeabilization, peripheral nerve excitation and cell blebbing, can be reduced or cancelled by applying another pulse of reversed polarity. Depending on the degree of cancellation, the pulse interval of these two pulses can be as long as dozens of microseconds. The cancellation effect diminishes as the pulse duration increases. To study the cancellation effect and potentially utilize it in electrotherapy, nanosecond bipolar pulse generators must be made available. An overview of the generators is given in this paper. A pulse forming line (PFL) that is matched at one end and shorted at the other end allows a bipolar pulse to be produced, but no delay can be inserted between the phases. Another generator employs a combination of a resistor, an inductor and a capacitor to form an RLC resonant circuit so that a bipolar pulse with a decaying magnitude can be generated. A third generator is a converter, which converts an existing unipolar pulse to a bipolar pulse. This is done by inserting an inductor in a transmission line. The first phase of the bipolar pulse is provided by the unipolar pulse's rising phase. The second phase is formed during the fall time of the unipolar pulse, when the inductor, which was previously charged during the flat part of the unipolar pulse, discharges its current to the load. The fourth type of generator uses multiple MOSFET switches stacked to turn on a pre-charged, bipolar RC network. This approach is the most flexible in that it can generate multiphasic pulses that have different amplitudes, delays, and durations. However, it may not be suitable for producing short nanosecond pulses (<100 ns), whereas the PFL approach and the RLC approach with gas switches are used for this range. Thus, each generator has its own advantages and applicable range. Copyright © 2018 Elsevier B.V. All rights reserved.

Stacks with TiN/titanium as the bipolar plate for PEMFCs

International Nuclear Information System (INIS)

Ren, Zhijun; Zhang, Dongming; Wang, Zaiyi

2012-01-01

Proton exchange membrane fuel cell (PEMFC) is a potential alternative for the internal combustion engine. But many problems, such as metallic bipolar plate instead of graphite bipolar plate to decrease the cost, should be solved before its application. Based on the previous results that single cell with TiN/Ti as bipolar plates shows high performance and enough long-time durability, the progress on the stacks with TiN/Ti as bipolar plates is reported in this manuscript. Till now seldom report is focused on stacks because of the complicated processing technique, especially for that with TiN/Ti as bipolar plate. The flow field in the plate is punched from titanium deformation, and two plates are welded by laser welding to form one piece of bipolar plate. The adopted processing techniques for stacks with TiN/Ti as bipolar plate exhibit advantage and feasibility in industry. The power density by weight for the stack is as high as 1353 W kg −1 , although it still has space to be improved. Next work should be focused on the design of flow channel parameters and flow field type based on plastic deformation of metal materials. -- Highlights: ► The progress on the stacks with TiN/Ti as bipolar plates is reported. ► The adopted processing techniques exhibit feasibility in industry. ► The power density by weight for the stack is as high as 1353 W kg −1 .

Progression along the Bipolar Spectrum: A Longitudinal Study of Predictors of Conversion from Bipolar Spectrum Conditions to Bipolar I and II Disorders

Science.gov (United States)

Alloy, Lauren B.; Urošević, Snežana; Abramson, Lyn Y.; Jager-Hyman, Shari; Nusslock, Robin; Whitehouse, Wayne G.; Hogan, Michael

2011-01-01

Little longitudinal research has examined progression to more severe bipolar disorders in individuals with “soft” bipolar spectrum conditions. We examine rates and predictors of progression to bipolar I and II diagnoses in a non-patient sample of college-age participants (n = 201) with high General Behavior Inventory scores and childhood or adolescent onset of “soft” bipolar spectrum disorders followed longitudinally for 4.5 years from the Longitudinal Investigation of Bipolar Spectrum (LIBS) project. Of 57 individuals with initial cyclothymia or bipolar disorder not otherwise specified (BiNOS) diagnoses, 42.1% progressed to a bipolar II diagnosis and 10.5% progressed to a bipolar I diagnosis. Of 144 individuals with initial bipolar II diagnoses, 17.4% progressed to a bipolar I diagnosis. Consistent with hypotheses derived from the clinical literature and the Behavioral Approach System (BAS) model of bipolar disorder, and controlling for relevant variables (length of follow-up, initial depressive and hypomanic symptoms, treatment-seeking, and family history), high BAS sensitivity (especially BAS Fun Seeking) predicted a greater likelihood of progression to bipolar II disorder, whereas early age of onset and high impulsivity predicted a greater likelihood of progression to bipolar I (high BAS sensitivity and Fun-Seeking also predicted progression to bipolar I when family history was not controlled). The interaction of high BAS and high Behavioral Inhibition System (BIS) sensitivities also predicted greater likelihood of progression to bipolar I. We discuss implications of the findings for the bipolar spectrum concept, the BAS model of bipolar disorder, and early intervention efforts. PMID:21668080

Losses of immunoreactive parvalbumin amacrine and immunoreactive alphaprotein kinase C bipolar cells caused by methylmercury chloride intoxication in the retina of the tropical fish Hoplias malabaricus

Directory of Open Access Journals (Sweden)

D.M.O. Bonci

2006-03-01

Full Text Available To quantify the effects of methylmercury (MeHg on amacrine and on ON-bipolar cells in the retina, experiments were performed in MeHg-exposed groups of adult trahiras (Hoplias malabaricus at two dose levels (2 and 6 µg/g, ip. The retinas of test and control groups were processed by mouse anti-parvalbumin and rabbit anti-alphaprotein kinase C (alphaPKC immunocytochemistry. Morphology and soma location in the inner nuclear layer were used to identify immunoreactive parvalbumin (PV-IR and alphaPKC (alphaPKC-IR in wholemount preparations. Cell density, topography and isodensity maps were estimated using confocal images. PV-IR was detected in amacrine cells in the inner nuclear layer and in displaced amacrine cells from the ganglion cell layer, and alphaPKC-IR was detected in ON-bipolar cells. The MeHg-treated group (6 µg/g showed significant reduction of the ON-bipolar alphaPKC-IR cell density (mean density = 1306 ± 393 cells/mm² compared to control (1886 ± 892 cells/mm²; P < 0.001. The mean densities found for amacrine PV-IR cells in MeHg-treated retinas were 1040 ± 56 cells/mm² (2 µg/g and 845 ± 82 cells/mm² (6 µg/g, also lower than control (1312 ± 31 cells/mm²; P < 0.05, differently from the data observed in displaced PV-IR amacrine cells. These results show that MeHg changed the PV-IR amacrine cell density in a dose-dependent way, and reduced the density of alphaKC-IR bipolar cells at the dose of 6 µg/g. Further studies are needed to identify the physiological impact of these findings on visual function.

The effects of mindfulness-based cognitive therapy in patients with bipolar disorder: a controlled functional MRI investigation.

Science.gov (United States)

Ives-Deliperi, Victoria L; Howells, Fleur; Stein, Dan J; Meintjes, Ernesta M; Horn, Neil

2013-09-25

Preliminary research findings have shown that mindfulness-based cognitive therapy improves anxiety and depressive symptoms in bipolar disorder. In this study, we further investigated the effects of MBCT in bipolar disorder, in a controlled fMRI study. Twenty three patients with bipolar disorder underwent neuropsychological testing and functional MRI. Sixteen of these patients were tested before and after an eight-week MBCT intervention, and seven were wait listed for training and tested at the same intervals. The results were compared with 10 healthy controls. Prior to MBCT, bipolar patients reported significantly higher levels of anxiety and symptoms of stress, scored significantly lower on a test of working memory, and showed significant BOLD signal decrease in the medial PFC during a mindfulness task, compared to healthy controls. Following MBCT, there were significant improvements in the bipolar treatment group, in measures of mindfulness, anxiety and emotion regulation, and in tests of working memory, spatial memory and verbal fluency compared to the bipolar wait list group. BOLD signal increases were noted in the medial PFC and posterior parietal lobe, in a repeat mindfulness task. A region of interest analysis revealed strong correlation between signal changes in medial PFC and increases in mindfulness. The small control group is a limitation in the study. These data suggest that MBCT improves mindfulness and emotion regulation and reduces anxiety in bipolar disorder, corresponding to increased activations in the medial PFC, a region associated with cognitive flexibility and previously proposed as a key area of pathophysiology in the disorder. © 2013 Elsevier B.V. All rights reserved.

A YinYang bipolar fuzzy cognitive TOPSIS method to bipolar disorder diagnosis.

Science.gov (United States)

Han, Ying; Lu, Zhenyu; Du, Zhenguang; Luo, Qi; Chen, Sheng

2018-05-01

Bipolar disorder is often mis-diagnosed as unipolar depression in the clinical diagnosis. The main reason is that, different from other diseases, bipolarity is the norm rather than exception in bipolar disorder diagnosis. YinYang bipolar fuzzy set captures bipolarity and has been successfully used to construct a unified inference mathematical modeling method to bipolar disorder clinical diagnosis. Nevertheless, symptoms and their interrelationships are not considered in the existing method, circumventing its ability to describe complexity of bipolar disorder. Thus, in this paper, a YinYang bipolar fuzzy multi-criteria group decision making method to bipolar disorder clinical diagnosis is developed. Comparing with the existing method, the new one is more comprehensive. The merits of the new method are listed as follows: First of all, multi-criteria group decision making method is introduced into bipolar disorder diagnosis for considering different symptoms and multiple doctors' opinions. Secondly, the discreet diagnosis principle is adopted by the revised TOPSIS method. Last but not the least, YinYang bipolar fuzzy cognitive map is provided for the understanding of interrelations among symptoms. The illustrated case demonstrates the feasibility, validity, and necessity of the theoretical results obtained. Moreover, the comparison analysis demonstrates that the diagnosis result is more accurate, when interrelations about symptoms are considered in the proposed method. In a conclusion, the main contribution of this paper is to provide a comprehensive mathematical approach to improve the accuracy of bipolar disorder clinical diagnosis, in which both bipolarity and complexity are considered. Copyright © 2018 Elsevier B.V. All rights reserved.

Does bipolar pacemaker current activate blood platelets?

DEFF Research Database (Denmark)

Gjesdal, Grunde; Hansen, Annebirthe Bo; Brandes, Axel

2009-01-01

OBJECTIVE: The aim of this study was to investigate whether bipolar pacemaker current lead can activate blood platelets. The null hypothesis was that 1 minute of electrical stimulation of platelets would not influence their subsequent reactivity to adenosine diphosphate (ADP). BACKGROUND: Both...... platelets and muscle cells contain actin and myosin filaments, and both cells are activated following calcium influx. Muscle cells open their calcium channels and contract when exposed to an electric current. Current through a bipolar pacemaker lead will expose a small volume of blood, including platelets......, to the depolarizing current. Platelet activation may ensue, resulting in aggregation, release reaction, and contraction. In contrast, a unipolar pacemaker system will not depolarize blood, but transmit current directly into the myocardium, and the current afterward passes through other tissues before returning...

Evaluation of materials for bipolar plates in simulated PEM fuel-cell cathodic environments

Energy Technology Data Exchange (ETDEWEB)

Rivas, S.V.; Belmonte, M.R.; Moron, L.E.; Torres, J.; Orozco, G. [Centro de Investigacion y Desarrollo Technologico en Electroquimica S.C. Parcque Sanfandila, Queretaro (Mexico); Perez-Quiroz, J.T. [Mexican Transport Inst., Queretaro (Mexico); Cortes, M. A. [Mexican Petroleum Inst., Mexico City (Mexico)

2008-04-15

The bipolar plates in proton exchange membrane fuel cells (PEMFC) are exposed to an oxidizing environment on the cathodic side, and therefore are susceptible to corrosion. Corrosion resistant materials are needed for the bipolar plates in order to improve the lifespan of fuel cells. This article described a study in which a molybdenum (Mo) coating was deposited over austenitic stainless steel 316 and carbon steel as substrates in order to evaluate the resulting surfaces with respect to their corrosion resistance in simulated anodic and cathodic PEMFC environments. The molybdenum oxide films were characterized by scanning electron microscopy (SEM) and Raman spectroscopy. The article presented the experiment and discussed the results of the corrosion behaviour of coated stainless steel. In general, the electrochemical characterization of bare materials and coated steel consisted of slow potentiodynamic polarization curves followed by a constant potential polarization test. The test medium was 0.5M sulfuric acid with additional introduction of oxygen to simulate the cathodic environment. All tests were performed at ambient temperature and at 50 degrees Celsius. The potentiostat used was a Gamry instrument. It was concluded that it is possible to deposit Mo-oxides on steel without using another alloying metal. The preferred substrate for corrosion prevention was found to be an alloy with high chromium content. 24 refs., 4 figs.

Genetic utility of broadly defined bipolar schizoaffective disorder as a diagnostic concept

Science.gov (United States)

Hamshere, M. L.; Green, E. K.; Jones, I. R.; Jones, L.; Moskvina, V.; Kirov, G.; Grozeva, D.; Nikolov, I.; Vukcevic, D.; Caesar, S.; Gordon-Smith, K.; Fraser, C.; Russell, E.; Breen, G.; St Clair, D.; Collier, D. A.; Young, A. H.; Ferrier, I. N.; Farmer, A.; McGuffin, P.; Holmans, P. A.; Owen, M. J.; O’Donovan, M. C.; Craddock, N.

2009-01-01

Background Psychiatric phenotypes are currently defined according to sets of descriptive criteria. Although many of these phenotypes are heritable, it would be useful to know whether any of the various diagnostic categories in current use identify cases that are particularly helpful for biological–genetic research. Aims To use genome-wide genetic association data to explore the relative genetic utility of seven different descriptive operational diagnostic categories relevant to bipolar illness within a large UK case–control bipolar disorder sample. Method We analysed our previously published Wellcome Trust Case Control Consortium (WTCCC) bipolar disorder genome-wide association data-set, comprising 1868 individuals with bipolar disorder and 2938 controls genotyped for 276 122 single nucleotide polymorphisms (SNPs) that met stringent criteria for genotype quality. For each SNP we performed a test of association (bipolar disorder group v. control group) and used the number of associated independent SNPs statistically significant at Pschizoaffective disorder, bipolar type; DSM–IV: bipolar I disorder; bipolar II disorder; schizoaffective disorder, bipolar type. Results The RDC schizoaffective disorder, bipolar type (v. controls) stood out from the other diagnostic subsets as having a significant excess of independent association signals (Pschizoaffective features have either a particularly strong genetic contribution or that, as a group, are genetically more homogeneous than the other phenotypes tested. The results point to the importance of using diagnostic approaches that recognise this group of individuals. Our approach can be applied to similar data-sets for other psychiatric and non-psychiatric phenotypes. PMID:19567891

Assessing the utility of bipolar membranes for use in photoelectrochemical water-splitting cells.

Science.gov (United States)

Vargas-Barbosa, Nella M; Geise, Geoffrey M; Hickner, Michael A; Mallouk, Thomas E

2014-11-01

Membranes are important in water-splitting solar cells because they prevent crossover of hydrogen and oxygen. Here, bipolar membranes (BPMs) were tested as separators in water electrolysis cells. Steady-state membrane and solution resistances, electrode overpotentials, and pH gradients were measured at current densities relevant to solar photoelectrolysis. Under forward bias conditions, electrodialysis of phosphate buffer ions creates a pH gradient across a BPM. Under reverse bias, the BPM can maintain a constant buffer pH on both sides of the cell, but a large membrane potential develops. Thus, the BPM does not present a viable solution for electrolysis in buffered electrolytes. However, the membrane potential is minimized when the anode and cathode compartments of the cell contain strongly basic and acidic electrolytes, respectively. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Characterization of Thermal and Mechanical Properties of Polypropylene-Based Composites for Fuel Cell Bipolar Plates and Development of Educational Tools in Hydrogen and Fuel Cell Technologies

Science.gov (United States)

Lopez Gaxiola, Daniel

2011-01-01

In this project we developed conductive thermoplastic resins by adding varying amounts of three different carbon fillers: carbon black (CB), synthetic graphite (SG) and multi-walled carbon nanotubes (CNT) to a polypropylene matrix for application as fuel cell bipolar plates. This component of fuel cells provides mechanical support to the stack,…

Electronic monitoring in bipolar disorder.

Science.gov (United States)

Faurholt-Jepsen, Maria

2018-03-01

Major reasons for the insufficient effects of current treatment options in bipolar disorder include delayed intervention for prodromal depressive and manic symptoms and decreased adherence to psychopharmacological treatment. The reliance on subjective information and clinical evaluations when diagnosing and assessing the severity of depressive and manic symptoms calls for less biased and more objective markers. By using electronic devices, fine-grained data on complex psychopathological aspects of bipolar disorder can be evaluated unobtrusively over the long term. Moreover, electronic data could possibly represent candidate markers of diagnosis and illness activity in bipolar disorder and allow for early and individualized intervention for prodromal symptoms outside clinical settings. 
The present dissertation concerns the use of electronic monitoring as a marker and treatment intervention in bipolar disorder and investigated the scientific literature and body of evidence within the area, which includes ten original study reports and two systematic reviews, one of which included a meta-analysis, conducted by the author of the dissertation. 
Taken together, the literature presented in this dissertation illustrates that 1) smartphone-based electronic self-monitoring of mood seems to reflect clinically assessed depressive and manic symptoms and enables the long-term characterization of mood

instability in bipolar disorder; 2) preliminary results suggest that smartphone-based automatically generated data (e.g. the number of text messages sent/day; the number of incoming and outgoing calls/day; the number of changes in cell tower IDs/day; and voice features) seem to reflect clinically assessed depressive and manic symptoms in bipolar disorder; 3) smartphone-based electronic self-monitoring had no effects on the severity of depressive and manic symptoms in bipolar disorder, according to a randomized controlled trial; and 4) electronic monitoring of psychomotor

Triangle bipolar pulse shaping and pileup correction based on DSP

International Nuclear Information System (INIS)

Esmaeili-sani, Vahid; Moussavi-zarandi, Ali; Akbar-ashrafi, Nafiseh; Boghrati, Behzad

2011-01-01

Programmable Digital Signal Processing (DSP) microprocessors are capable of doing complex discrete signal processing algorithms with clock rates above 50 MHz. This combined with their low expense, ease of use and selected dedicated hardware make them an ideal option for spectrometer data acquisition systems. For this generation of spectrometers, functions that are typically performed in dedicated circuits, or offline, are being migrated to the field programmable gate array (FPGA). This will not only reduce the electronics, but the features of modern FPGAs can be utilized to add considerable signal processing power to produce higher resolution spectra. In this paper we report on an all-digital triangle bipolar pulse shaping and pileup correction algorithm that is being developed for the DSP. The pileup mitigation algorithm will allow the spectrometers to run at higher count rates or with multiple sources without imposing large data losses due to the overlapping of scintillation signals. This correction technique utilizes a very narrow bipolar triangle digital pulse shaping algorithm to extract energy information for most pileup events.

Triangle bipolar pulse shaping and pileup correction based on DSP

Energy Technology Data Exchange (ETDEWEB)

Esmaeili-sani, Vahid, E-mail: vaheed_esmaeely80@yahoo.com [Department of Nuclear Engineering and Physics, Amirkabir University of Technology, P.O. Box 4155-4494, Tehran (Iran, Islamic Republic of); Moussavi-zarandi, Ali; Akbar-ashrafi, Nafiseh; Boghrati, Behzad [Department of Nuclear Engineering and Physics, Amirkabir University of Technology, P.O. Box 4155-4494, Tehran (Iran, Islamic Republic of)

2011-02-11

Programmable Digital Signal Processing (DSP) microprocessors are capable of doing complex discrete signal processing algorithms with clock rates above 50 MHz. This combined with their low expense, ease of use and selected dedicated hardware make them an ideal option for spectrometer data acquisition systems. For this generation of spectrometers, functions that are typically performed in dedicated circuits, or offline, are being migrated to the field programmable gate array (FPGA). This will not only reduce the electronics, but the features of modern FPGAs can be utilized to add considerable signal processing power to produce higher resolution spectra. In this paper we report on an all-digital triangle bipolar pulse shaping and pileup correction algorithm that is being developed for the DSP. The pileup mitigation algorithm will allow the spectrometers to run at higher count rates or with multiple sources without imposing large data losses due to the overlapping of scintillation signals. This correction technique utilizes a very narrow bipolar triangle digital pulse shaping algorithm to extract energy information for most pileup events.

Calcium Signaling in Taste Cells

Science.gov (United States)

Medler, Kathryn F.

2014-01-01

The sense of taste is a common ability shared by all organisms and is used to detect nutrients as well as potentially harmful compounds. Thus taste is critical to survival. Despite its importance, surprisingly little is known about the mechanisms generating and regulating responses to taste stimuli. All taste responses depend on calcium signals to generate appropriate responses which are relayed to the brain. Some taste cells have conventional synapses and rely on calcium influx through voltage-gated calcium channels. Other taste cells lack these synapses and depend on calcium release to formulate an output signal through a hemichannel. Beyond establishing these characteristics, few studies have focused on understanding how these calcium signals are formed. We identified multiple calcium clearance mechanisms that regulate calcium levels in taste cells as well as a calcium influx that contributes to maintaining appropriate calcium homeostasis in these cells. Multiple factors regulate the evoked taste signals with varying roles in different cell populations. Clearly, calcium signaling is a dynamic process in taste cells and is more complex than has previously been appreciated. PMID:25450977

Bipolar disorders

DEFF Research Database (Denmark)

Vieta, Eduard; Berk, Michael; Schulze, Thomas G

2018-01-01

Bipolar disorders are chronic and recurrent disorders that affect >1% of the global population. Bipolar disorders are leading causes of disability in young people as they can lead to cognitive and functional impairment and increased mortality, particularly from suicide and cardiovascular disease...... and accurate diagnosis is difficult in clinical practice as the onset of bipolar disorder is commonly characterized by nonspecific symptoms, mood lability or a depressive episode, which can be similar in presentation to unipolar depression. Moreover, patients and their families do not always understand...... a bipolar disorder from other conditions. Optimal early treatment of patients with evidence-based medication (typically mood stabilizers and antipsychotics) and psychosocial strategies is necessary....

Signaling profiling at the single-cell level identifies a distinct signaling signature in murine hematopoietic stem cells.

Science.gov (United States)

Du, Juan; Wang, Jinyong; Kong, Guangyao; Jiang, Jing; Zhang, Jingfang; Liu, Yangang; Tong, Wei; Zhang, Jing

2012-07-01

Hematopoietic stem cell (HSC) function is tightly regulated by cytokine signaling. Although phospho-flow cytometry allows us to study signaling in defined populations of cells, there has been tremendous hurdle to carry out this study in rare HSCs due to unrecoverable critical HSC markers, low HSC number, and poor cell recovery rate. Here, we overcame these difficulties and developed a "HSC phospho-flow" method to analyze cytokine signaling in murine HSCs at the single-cell level and compare HSC signaling profile to that of multipotent progenitors (MPPs), a cell type immediately downstream of HSCs, and commonly used Lin(-) cKit(+) cells (LK cells, enriched for myeloid progenitors). We chose to study signaling evoked from three representative cytokines, stem cell factor (SCF) and thrombopoietin (TPO) that are essential for HSC function and granulocyte macrophage-colony-stimulating factor (GM-CSF) that is dispensable for HSCs. HSCs display a distinct TPO and GM-CSF signaling signature from MPPs and LK cells, which highly correlates with receptor surface expression. In contrast, although majority of LK cells express lower levels of cKit than HSCs and MPPs, SCF-evoked ERK1/2 activation in LK cells shows a significantly increased magnitude for a prolonged period. These results suggest that specific cellular context plays a more important role than receptor surface expression in SCF signaling. Our study of HSC signaling at the homeostasis stage paves the way to investigate signaling changes in HSCs under conditions of stress, aging, and hematopoietic diseases. Copyright © 2012 AlphaMed Press.

Neutrality in bipolar structures

DEFF Research Database (Denmark)

Montero, Javier; Rodríguez, J. Tinguaro; Franco, Camilo

2014-01-01

In this paper, we want to stress that bipolar knowledge representation naturally allows a family of middle states which define as a consequence different kinds of bipolar structures. These bipolar structures are deeply related to the three types of bipolarity introduced by Dubois and Prade, but our...... approach offers a systematic explanation of how such bipolar structures appear and can be identified....

Accurate automatic tuning circuit for bipolar integrated filters

NARCIS (Netherlands)

de Heij, Wim J.A.; de Heij, W.J.A.; Hoen, Klaas; Hoen, Klaas; Seevinck, Evert; Seevinck, E.

1990-01-01

An accurate automatic tuning circuit for tuning the cutoff frequency and Q-factor of high-frequency bipolar filters is presented. The circuit is based on a voltage controlled quadrature oscillator (VCO). The frequency and the RMS (root mean square) amplitude of the oscillator output signal are

Multilayer graphene for long-term corrosion protection of stainless steel bipolar plates for polymer electrolyte membrane fuel cell

DEFF Research Database (Denmark)

Stoot, Adam Carsten; Camilli, Luca; Spiegelhauer, Susie Ann

2015-01-01

Abstract Motivated by similar investigations recently published (Pu et al., 2015), we report a comparative corrosion study of three sets of samples relevant as bipolar plates for polymer electrolyte fuel cells: stainless steel, stainless steel with a nickel seed layer (Ni/SS) and stainless steel...

Neurofunctional changes in adolescent cannabis users with and without bipolar disorder.

Science.gov (United States)

Bitter, Samantha M; Adler, Caleb M; Eliassen, James C; Weber, Wade A; Welge, Jeffrey A; Burciaga, Joaquin; Shear, Paula K; Strakowski, Stephen M; DelBello, Melissa P

2014-11-01

To compare regional brain activation among adolescents with bipolar disorder and co-occurring cannabis use disorder. Cross-sectional study. Cincinnati, OH, USA. Adolescents with bipolar disorder (BP, n = 14), adolescents with cannabis use disorder (MJ, n = 13), adolescents with co-occurring cannabis use and bipolar disorders (BPMJ, n = 25) and healthy adolescents (HC, n = 15). Cannabis craving, substance use, Blood Oxygenation Level Dependent (BOLD) signal assessed by the Marijuana Craving Questionnaire (MCQ), Teen-Addiction Severity Index (T-ASI) and a cannabis cue-reactivity task during a functional magnetic resonance imaging (fMRI) session, respectively. The BP group exhibited significantly greater brain activation than the BPMJ group in the right amygdala (F = 4.14, P = 0.046), left nucleus accumbens (F = 3.8, P = 0.02), left thalamus (F = 3.8, P adolescents with comorbid cannabis use do not exhibit the same over-activation of the regions involved in emotional processing as seen in adolescents with bipolar disorder alone. The absence of these findings in patients with comorbid bipolar and cannabis use disorders suggests that these individuals may have a unique endophenotype of bipolar disorder or that cannabis use may alter brain activation uniquely in bipolar disorder patients who use cannabis. © 2014 Society for the Study of Addiction.

Tritium separation from light and heavy water by bipolar electrolysis

International Nuclear Information System (INIS)

Petek, M.; Ramey, D.W.; Taylor, R.D.

1981-01-01

Using multiple bipolar electrolytic separation of hydrogen isotopes with Pd-25%Ag electrodes, the mathematical feasibility of this method for tritium separation was shown and experimentally verified. Separation factors were measured on single bipolar electrodes and were found to be approximately equivalent to those associated with individual ordinary electrolytic systems. Multibipolar separations were experimentally achieved in single cascaded cells in which each bipolar electrode was of equal area to others in a series arrangement. Factors measured for multibipolar H-D separation were close to the values measured in single-stage cell measurements; for H-T separation, interstage leakage reduced the measured separation factor. However, in both cases separation of sufficient magnitude was achieved to show feasibility for real application to the extraction of tritium from large-volume systems at high current density. (author)

The thermodynamics of bipolarity: a bifurcation model of bipolar illness and bipolar character and its psychotherapeutic applications.

Science.gov (United States)

Sabelli, H C; Carlson-Sabelli, L; Javaid, J I

1990-11-01

Two models dominate current formulations of bipolar illness: the homeostatic model implicit in Freud's psychodynamics and most neuroamine deficit/excess theories; and the oscillatory model of exaggerated biological rhythms. The homeostatic model is based on the closed systems approach of classic thermodynamics, while the oscillatory model requires the open systems approach of modern thermodynamics. Here we present a thermodynamic model of bipolarity that includes both homeostatic and oscillatory features and adds the most important feature of open systems thermodynamics: the creation of novel structures in bifurcation processes. According to the proposed model, bipolarity is the result of exaggerated biological energy that augments homeostatic, oscillatory and creative psychological processes. Only low-energy closed systems tend to rest ("point attractor") and entropic disorder. Open processes containing and exchanging energy fluctuate between opposite states ("periodic attractors"); they are characteristic of most physiological rhythms and are exaggerated in bipolar subjects. At higher energies, their strong fluctuations destroy pre-existing patterns and structures, produce turbulence ("chaotic attractors"), which sudden switches between opposite states, and create new and more complex structures. Likewise, high-energy bipolars develop high spontaneity, great fluctuations between opposite moods, internal and interpersonal chaos, and enhanced creativity (personal, artistic, professional) as well as psychopathology (personality deviations, psychotic delusions). Offered here is a theoretical explanation of the dual--creative and destructive--nature of bipolarity in terms of the new enantiodromic concept of entropy generalized by process theory. Clinically, this article offers an integrative model of bipolarity that accounts for many clinical features and contributes to a definition of the bipolar personality.

Eliminating Glutamatergic Input onto Horizontal Cells Changes the Dynamic Range and Receptive Field Organization of Mouse Retinal Ganglion Cells.

Science.gov (United States)

Ströh, Sebastian; Puller, Christian; Swirski, Sebastian; Hölzel, Maj-Britt; van der Linde, Lea I S; Segelken, Jasmin; Schultz, Konrad; Block, Christoph; Monyer, Hannah; Willecke, Klaus; Weiler, Reto; Greschner, Martin; Janssen-Bienhold, Ulrike; Dedek, Karin

2018-02-21

In the mammalian retina, horizontal cells receive glutamatergic inputs from many rod and cone photoreceptors and return feedback signals to them, thereby changing photoreceptor glutamate release in a light-dependent manner. Horizontal cells also provide feedforward signals to bipolar cells. It is unclear, however, how horizontal cell signals also affect the temporal, spatial, and contrast tuning in retinal output neurons, the ganglion cells. To study this, we generated a genetically modified mouse line in which we eliminated the light dependency of feedback by deleting glutamate receptors from mouse horizontal cells. This genetic modification allowed us to investigate the impact of horizontal cells on ganglion cell signaling independent of the actual mode of feedback in the outer retina and without pharmacological manipulation of signal transmission. In control and genetically modified mice (both sexes), we recorded the light responses of transient OFF-α retinal ganglion cells in the intact retina. Excitatory postsynaptic currents (EPSCs) were reduced and the cells were tuned to lower temporal frequencies and higher contrasts, presumably because photoreceptor output was attenuated. Moreover, receptive fields of recorded cells showed a significantly altered surround structure. Our data thus suggest that horizontal cells are responsible for adjusting the dynamic range of retinal ganglion cells and, together with amacrine cells, contribute to the center/surround organization of ganglion cell receptive fields in the mouse. SIGNIFICANCE STATEMENT Horizontal cells represent a major neuronal class in the mammalian retina and provide lateral feedback and feedforward signals to photoreceptors and bipolar cells, respectively. The mode of signal transmission remains controversial and, moreover, the contribution of horizontal cells to visual processing is still elusive. To address the question of how horizontal cells affect retinal output signals, we recorded the light

Oxide bipolar electronics: materials, devices and circuits

International Nuclear Information System (INIS)

Grundmann, Marius; Klüpfel, Fabian; Karsthof, Robert; Schlupp, Peter; Schein, Friedrich-Leonhard; Splith, Daniel; Yang, Chang; Bitter, Sofie; Von Wenckstern, Holger

2016-01-01

We present the history of, and the latest progress in, the field of bipolar oxide thin film devices. As such we consider primarily pn-junctions in which at least one of the materials is a metal oxide semiconductor. A wide range of n-type and p-type oxides has been explored for the formation of such bipolar diodes. Since most oxide semiconductors are unipolar, challenges and opportunities exist with regard to the formation of heterojunction diodes and band lineups. Recently, various approaches have led to devices with high rectification, namely p-type ZnCo 2 O 4 and NiO on n-type ZnO and amorphous zinc-tin-oxide. Subsequent bipolar devices and applications such as photodetectors, solar cells, junction field-effect transistors and integrated circuits like inverters and ring oscillators are discussed. The tremendous progress shows that bipolar oxide electronics has evolved from the exploration of various materials and heterostructures to the demonstration of functioning integrated circuits. Therefore a viable, facile and high performance technology is ready for further exploitation and performance optimization. (topical review)

Single-event burnout of epitaxial bipolar transistors

Energy Technology Data Exchange (ETDEWEB)

Kuboyama, S.; Sugimoto, K.; Shugyo, S.; Matsuda, S. [National Space Development Agency of Japan, Tsukuba, Ibaraki (Japan); Hirao, T. [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan)

1998-12-01

Single-Event Burnout (SEB) of bipolar junction transistors (BJTs) has been observed nondestructively. It was revealed that all the NPN BJTs, including small signal transistors, with thinner epitaxial layers were inherently susceptible to the SEB phenomenon. It was demonstrated that several design parameters of BJTs were responsible for SEB susceptibility. Additionally, destructive and nondestructive modes of SEB were identified.

The bipolar silicon microstrip detector: A proposal for a novel precision tracking device

International Nuclear Information System (INIS)

Horisberger, R.

1990-01-01

It is proposed to combine the technology of fully depleted microstrip detectors fabricated on n doped high resistivity silicon with the concept of the bipolar transistor. This is done by adding a n ++ doped region inside the normal p + implanted region of the reverse biased p + n diode. The resulting structure has amplifying properties and is referred to as bipaolar pixel transistor. The simplest readout scheme of a bipolar pixel array by an aluminium strip bus leads to the bipolar microstrip detector. The bipolar pixel structure is expected to give a better signal-to-noise performance for the detection of minimum ionizing charged particle tracks than the normal silicon diode strip detector and therefore should allow in future the fabrication of thinner silicon detectors for precision tracking. (orig.)

Bipolar disorder in adolescence.

Science.gov (United States)

DeFilippis, Melissa; Wagner, Karen Dineen

2013-08-01

Bipolar disorder is a serious psychiatric condition that may have onset in childhood. It is important for physicians to recognize the symptoms of bipolar disorder in children and adolescents in order to accurately diagnose this illness early in its course. Evidence regarding the efficacy of various treatments is necessary to guide the management of bipolar disorder in youth. For example, several medications commonly used for adults with bipolar disorder have not shown efficacy for children and adolescents with bipolar disorder. This article reviews the prevalence, diagnosis, course, and treatment of bipolar disorder in children and adolescents and provides physicians with information that will aid in diagnosis and treatment.

Regulation of glycogen synthase kinase-3 during bipolar mania treatment.

Science.gov (United States)

Li, Xiaohong; Liu, Min; Cai, Zhuoji; Wang, Gang; Li, Xiaohua

2010-11-01

Bipolar disorder is a debilitating psychiatric illness presenting with recurrent mania and depression. The pathophysiology of bipolar disorder is poorly understood, and molecular targets in the treatment of bipolar disorder remain to be identified. Preclinical studies have suggested that glycogen synthase kinase-3 (GSK3) is a potential therapeutic target in bipolar disorder, but evidence of abnormal GSK3 in human bipolar disorder and its response to treatment is still lacking. This study was conducted in acutely ill type I bipolar disorder subjects who were hospitalized for a manic episode. The protein level and the inhibitory serine phosphorylation of GSK3 in peripheral blood mononuclear cells of bipolar manic and healthy control subjects were compared, and the response of GSK3 to antimanic treatment was evaluated. The levels of GSK3α and GSK3β in this group of bipolar manic subjects were higher than healthy controls. Symptom improvement during an eight-week antimanic treatment with lithium, valproate, and atypical antipsychotics was accompanied by a significant increase in the inhibitory serine phosphorylation of GSK3, but not the total level of GSK3, whereas concomitant electroconvulsive therapy treatment during a manic episode appeared to dampen the response of GSK3 to pharmacological treatment. Results of this study suggest that GSK3 can be modified during the treatment of bipolar mania. This finding in human bipolar disorder is in agreement with preclinical data suggesting that inhibition of GSK3 by increasing serine phosphorylation is a response of GSK3 to psychotropics used in bipolar disorder, supporting the notion that GSK3 is a promising molecular target in the pharmacological treatment of bipolar disorder. © 2010 John Wiley and Sons A/S.

Electronic monitoring in bipolar disorder

DEFF Research Database (Denmark)

Faurholt-Jepsen, Maria

2018-01-01

generated data (e.g. the number of text messages sent/day; the number of incoming and outgoing calls/day; the number of changes in cell tower IDs/day; and voice features) seem to reflect clinically assessed depressive and manic symptoms in bipolar disorder; 3) smartphone-based electronic self-monitoring had...

Gsk3 Signalling and Redox Status in Bipolar Disorder: Evidence from Lithium Efficacy

Directory of Open Access Journals (Sweden)

Antonina Luca

2016-01-01

Full Text Available Objective. To discuss the link between glycogen synthase kinase-3 (GSK3 and the main biological alterations demonstrated in bipolar disorder (BD, with special attention to the redox status and the evidence supporting the efficacy of lithium (a GSK3 inhibitor in the treatment of BD. Methods. A literature research on the discussed topics, using Pubmed and Google Scholar, has been conducted. Moreover, a manual selection of interesting references from the identified articles has been performed. Results. The main biological alterations of BD, pertaining to inflammation, oxidative stress, membrane ion channels, and circadian system, seem to be intertwined. The dysfunction of the GSK3 signalling pathway is involved in all the aforementioned “biological causes” of BD. In a complex scenario, it can be seen as the common denominator linking them all. Lithium inhibition of GSK3 could, at least in part, explain its positive effect on these biological dysfunctions and its superiority in terms of clinical efficacy. Conclusions. Deepening the knowledge on the molecular bases of BD is fundamental to identifying the biochemical pathways that must be targeted in order to provide patients with increasingly effective therapeutic tools against an invalidating disorder such as BD.

Cost and performance prospects for composite bipolar plates in fuel cells and redox flow batteries

Science.gov (United States)

Minke, Christine; Hickmann, Thorsten; dos Santos, Antonio R.; Kunz, Ulrich; Turek, Thomas

2016-02-01

Carbon-polymer-composite bipolar plates (BPP) are suitable for fuel cell and flow battery applications. The advantages of both components are combined in a product with high electrical conductivity and good processability in convenient polymer forming processes. In a comprehensive techno-economic analysis of materials and production processes cost factors are quantified. For the first time a technical cost model for BPP is set up with tight integration of material characterization measurements.

Bipolar Disorder

Science.gov (United States)

Bipolar disorder is a serious mental illness. People who have it go through unusual mood changes. They go ... The down feeling is depression. The causes of bipolar disorder aren't always clear. It runs in families. ...

Cell-Cell Contact Area Affects Notch Signaling and Notch-Dependent Patterning.

Science.gov (United States)

Shaya, Oren; Binshtok, Udi; Hersch, Micha; Rivkin, Dmitri; Weinreb, Sheila; Amir-Zilberstein, Liat; Khamaisi, Bassma; Oppenheim, Olya; Desai, Ravi A; Goodyear, Richard J; Richardson, Guy P; Chen, Christopher S; Sprinzak, David

2017-03-13

During development, cells undergo dramatic changes in their morphology. By affecting contact geometry, these morphological changes could influence cellular communication. However, it has remained unclear whether and how signaling depends on contact geometry. This question is particularly relevant for Notch signaling, which coordinates neighboring cell fates through direct cell-cell signaling. Using micropatterning with a receptor trans-endocytosis assay, we show that signaling between pairs of cells correlates with their contact area. This relationship extends across contact diameters ranging from micrometers to tens of micrometers. Mathematical modeling predicts that dependence of signaling on contact area can bias cellular differentiation in Notch-mediated lateral inhibition processes, such that smaller cells are more likely to differentiate into signal-producing cells. Consistent with this prediction, analysis of developing chick inner ear revealed that ligand-producing hair cell precursors have smaller apical footprints than non-hair cells. Together, these results highlight the influence of cell morphology on fate determination processes. Copyright © 2017 Elsevier Inc. All rights reserved.

Single-event burnout of epitaxial bipolar transistors

Energy Technology Data Exchange (ETDEWEB)

Kuboyama, Satoshi; Sugimoto, Kenji; Matsuda, Sumio [National Space Development Agency of Japan, Ysukuba, Ibaraki (Japan); Hirao, Toshio

1998-10-01

Single-event burnout (SEB) of bipolar junction transistors (BJTs) has been observed nondestructively. It was revealed that all the NPN BJTs including small signal transistors with thinner epitaxial layer were inherently susceptible to the SEB phenomenon. It was demonstrated that several design parameters of BJTs were responsible for SEB susceptibility. Additionally, destructive and nondestructive modes of SEB were identified. (author)

Scale-up of Carbon/Carbon Bipolar Plates

Energy Technology Data Exchange (ETDEWEB)

David P. Haack

2009-04-08

This project was focused upon developing a unique material technology for use in PEM fuel cell bipolar plates. The carbon/carbon composite material developed in this program is uniquely suited for use in fuel cell systems, as it is lightweight, highly conductive and corrosion resistant. The project further focused upon developing the manufacturing methodology to cost-effectively produce this material for use in commercial fuel cell systems. United Technology Fuel Cells Corp., a leading fuel cell developer was a subcontractor to the project was interested in the performance and low-cost potential of the material. The accomplishments of the program included the development and testing of a low-cost, fully molded, net-shape carbon-carbon bipolar plate. The process to cost-effectively manufacture these carbon-carbon bipolar plates was focused on extensively in this program. Key areas for cost-reduction that received attention in this program was net-shape molding of the detailed flow structures according to end-user design. Correlations between feature detail and process parameters were formed so that mold tooling could be accurately designed to meet a variety of flow field dimensions. A cost model was developed that predicted the cost of manufacture for the product in near-term volumes and long-term volumes (10+ million units per year). Because the roduct uses lowcost raw materials in quantities that are less than competitive tech, it was found that the cost of the product in high volume can be less than with other plate echnologies, and can meet the DOE goal of $4/kW for transportation applications. The excellent performance of the all-carbon plate in net shape was verified in fuel cell testing. Performance equivalent to much higher cost, fully machined graphite plates was found.

Novel multiple criteria decision making methods based on bipolar neutrosophic sets and bipolar neutrosophic graphs

OpenAIRE

Muhammad, Akram; Musavarah, Sarwar

2016-01-01

In this research study, we introduce the concept of bipolar neutrosophic graphs. We present the dominating and independent sets of bipolar neutrosophic graphs. We describe novel multiple criteria decision making methods based on bipolar neutrosophic sets and bipolar neutrosophic graphs. We also develop an algorithm for computing domination in bipolar neutrosophic graphs.

Modeling of charge transport in ion bipolar junction transistors.

Science.gov (United States)

Volkov, Anton V; Tybrandt, Klas; Berggren, Magnus; Zozoulenko, Igor V

2014-06-17

Spatiotemporal control of the complex chemical microenvironment is of great importance to many fields within life science. One way to facilitate such control is to construct delivery circuits, comprising arrays of dispensing outlets, for ions and charged biomolecules based on ionic transistors. This allows for addressability of ionic signals, which opens up for spatiotemporally controlled delivery in a highly complex manner. One class of ionic transistors, the ion bipolar junction transistors (IBJTs), is especially attractive for these applications because these transistors are functional at physiological conditions and have been employed to modulate the delivery of neurotransmitters to regulate signaling in neuronal cells. Further, the first integrated complementary ionic circuits were recently developed on the basis of these ionic transistors. However, a detailed understanding of the device physics of these transistors is still lacking and hampers further development of components and circuits. Here, we report on the modeling of IBJTs using Poisson's and Nernst-Planck equations and the finite element method. A two-dimensional model of the device is employed that successfully reproduces the main characteristics of the measurement data. On the basis of the detailed concentration and potential profiles provided by the model, the different modes of operation of the transistor are analyzed as well as the transitions between the different modes. The model correctly predicts the measured threshold voltage, which is explained in terms of membrane potentials. All in all, the results provide the basis for a detailed understanding of IBJT operation. This new knowledge is employed to discuss potential improvements of ion bipolar junction transistors in terms of miniaturization and device parameters.

Effect of surface treatment on the interfacial contact resistance and corrosion resistance of Fe–Ni–Cr alloy as a bipolar plate for polymer electrolyte membrane fuel cells

International Nuclear Information System (INIS)

Yang, Meijun; Zhang, Dongming

2014-01-01

The bipolar plate is an important component of the PEMFC (polymer electrolyte membrane fuel cell) because it supplies the pathway of electron flow between each unit cell. Fe–Ni–Cr alloy is considered as a good candidate material for bipolar plate, but it is limited to use as a bipolar plate due to its high ICR (interfacial contact resistance) and corrosion problem. In order to explore a cost-effective method on surface modification, various chemical and electrochemical treatments are performed on Fe–Ni–Cr alloy to acquire the effect of the surface modification on the ICR and corrosion behavior. The ICR and corrosion resistance of Fe–Ni–Cr alloy can be effectively controlled by the chemical treatment of immersion in the mixed acid solution with 10 vol% HNO 3 , 2 vol% HCl and 1 vol% HF for 10 min at 65 °C and then was placed in 30 vol% HNO 3 solution for 5 min. The chemical treatment is more effective on reducing ICR and improving corrosion resistance than that of electrochemical methods (be carried out in the 2 mol/L H 2 SO 4 solution with the electrical potential from −0.4 V to 0.6 V) for Fe–Ni–Cr alloy as a bipolar plate for polymer electrolyte membrane fuel cells. - Highlights: • The procedure of the surface treatments on Fe–Ni–Cr alloy as bipolar plate was described in detail. • Effects of various surface treatments on the interfacial contact resistivity and corrosion behavior were discussed. • The mechanism of the surface modification was particularly analyzed

Imunologia do transtorno bipolar Immunology of bipolar disorder

Directory of Open Access Journals (Sweden)

Izabela Guimarães Barbosa

2009-01-01

Full Text Available OBJETIVO: Pesquisas recentes têm implicado fatores imunes na patogênese de diversos transtornos neuropsiquiátricos. O objetivo do presente trabalho é revisar os trabalhos que investigaram a associação entre transtorno bipolar e alterações em parâmetros imunes. MÉTODOS: Artigos que incluíam as palavras-chave: "bipolar disorder", "mania", "immunology", "cytokines", "chemokines", "interleukins", "interferon" e "tumor necrosis factor" foram selecionados em uma revisão sistemática da literatura. As bases de dados avaliadas foram MedLine e Scopus, entre os anos de 1980 e 2008. RESULTADOS: Foram identificados 28 trabalhos que estudaram alterações imunes em pacientes com transtorno bipolar. Seis artigos investigaram genes relacionados à resposta imune; cinco, autoanticorpos; quatro, populações leucocitárias; 13, citocinas e/ou moléculas relacionadas à resposta imune e seis, leucócitos de pacientes in vitro. CONCLUSÕES: Embora haja evidências na literatura correlacionando o transtorno bipolar a alterações imunes, os dados não são conclusivos. O transtorno bipolar parece estar associado a níveis mais elevados de autoanticorpos circulantes, assim como à tendência à ativação imune com produção de citocinas pró-inflamatórias e redução de parâmetros anti-inflamatórios.OBJECTIVE: Emerging research has implicated immune factors in the pathogenesis of a variety of neuropsychiatric disorders. The objective of the present paper is to review the studies that investigated the association between bipolar disorder and immune parameters. METHODS: Papers that included the keywords "bipolar to disorder", "mania", "immunology", "cytokines", "chemokines", "interleukins", "interferon" and "tumor necrosis factor" were selected in a systematic review of the literature. The evaluated databases were MedLine and Scopus in the period between 1980 and 2008. RESULTS: Twenty eight works were found. Six studies investigated immune response

Genetic structure of personality factors and bipolar disorder in families segregating bipolar disorder.

Science.gov (United States)

Hare, Elizabeth; Contreras, Javier; Raventos, Henriette; Flores, Deborah; Jerez, Alvaro; Nicolini, Humberto; Ontiveros, Alfonso; Almasy, Laura; Escamilla, Michael

2012-02-01

Bipolar disorder (BPD) has been associated with variations in personality dimensions, but the nature of this relationship has been unclear. In this study, the heritabilities of BPD and the Big Five personality factors and the genetic correlations between BPD and personality factors are reported. The participants in this study were 1073 individuals from 172 families of Mexican or Central American ancestry. Heritabilities and genetic correlations were calculated under a polygenic model using the maximum-likelihood method of obtaining variance components implemented in the SOLAR software package. Heritabilities of 0.49, 0.43, and 0.43 were found for the narrowest phenotype (schizoaffective bipolar and bipolar I), the intermediate phenotype (schizoaffective bipolar, bipolar I, and bipolar II), and the broadest phenotype (schizoaffective bipolar, bipolar I, bipolar II, and recurrent depression), respectively. For the Big Five personality factors, heritabilities were 0.25 for agreeableness, 0.24 for conscientiousness, 0.24 for extraversion, 0.23 for neuroticism, and 0.32 for openness to experience. For the narrowest phenotype, a significant negative correlation (-0.32) with extraversion was found. For the broadest phenotype, negative correlations were found for agreeableness (-0.35), conscientiousness (-0.39), and extraversion (-0.44). A positive correlation (0.37) was found with neuroticism. It is not possible to determine whether aspects of personality are factors in the development of bipolar disorder or vice versa. The short form of the NEO does not provide the ability to examine in detail which facets of extraversion are most closely related to bipolar disorder or to compare our results with studies that have used the long version of the scale. This study establishes a partial genetic basis for the Big Five personality factors in this set of families, while the environmental variances demonstrate that non-genetic factors are also important in their influence on

Porous Composite for Bipolar Plate in Low Emission Hydrogen Fuel Cells

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Renata Katarzyna Włodarczyk

2018-01-01

Full Text Available The paper presents the results of graphite-stainless steel composites for the bipolar plates in low-temperature fuel cells. The sinters were performed by powder metallurgy technology. The influenceof technological parameters, especially molding pressure were examined. Following the requirements formulated by the DOE concerning the parameters of the materials, it indicated by the value of the parameters. The density, flowabilit, particle size of graphite and stainless steel powders have been evaluated. Composites have been tested by microstructure and phase analysis, properties of strength, functional properties: wettability, porosity, roughness. The special attention was paid to the analysis of corrosion resistance obtained sinters and influenceof technological parameters on the corrosion. Corrosion tests were carried out under conditions simulating the environment of the fuel cell under anode and cathode conditions. The effectof pH solution during working of the cell on corrosion resistance of composites have been evaluated. Contact resistance depends on roughness of sinters. Low ICR determined high contact area GDL-BP and high electrical conductivity on the contact surface. The ICR in anode conditions after corrosion tests are not change significantly; composite materials can be used for materials for B in terms of H 2 .

Nutrition and Bipolar Depression.

Science.gov (United States)

Beyer, John L; Payne, Martha E

2016-03-01

As with physical conditions, bipolar disorder is likely to be impacted by diet and nutrition. Patients with bipolar disorder have been noted to have relatively unhealthy diets, which may in part be the reason they also have an elevated risk of metabolic syndrome and obesity. An improvement in the quality of the diet should improve a bipolar patient's overall health risk profile, but it may also improve their psychiatric outcomes. New insights into biological dysfunctions that may be present in bipolar disorder have presented new theoretic frameworks for understanding the relationship between diet and bipolar disorder. Copyright © 2016 Elsevier Inc. All rights reserved.

Bipolar one diode-one resistor integration for high-density resistive memory applications.

Science.gov (United States)

Li, Yingtao; Lv, Hangbing; Liu, Qi; Long, Shibing; Wang, Ming; Xie, Hongwei; Zhang, Kangwei; Huo, Zongliang; Liu, Ming

2013-06-07

Different from conventional unipolar-type 1D-1R RRAM devices, a bipolar-type 1D-1R memory device concept is proposed and successfully demonstrated by the integration of Ni/TiOx/Ti diode and Pt/HfO2/Cu bipolar RRAM cell to suppress the undesired sneak current in a cross-point array. The bipolar 1D-1R memory device not only achieves self-compliance resistive switching characteristics by the reverse bias current of the Ni/TiOx/Ti diode, but also exhibits excellent bipolar resistive switching characteristics such as uniform switching, satisfactory data retention, and excellent scalability, which give it high potentiality for high-density integrated nonvolatile memory applications.

Comparison of methods for removing electromagnetic noise from electromyographic signals.

Science.gov (United States)

Defreitas, Jason M; Beck, Travis W; Stock, Matt S

2012-02-01

The purpose of this investigation was to compare three different methods of removing noise from monopolar electromyographic (EMG) signals: (a) electrical shielding with a Faraday cage, (b) denoising with a digital notch-filter and (c) applying a bipolar differentiation with another monopolar EMG signal. Ten men and ten women (mean age = 24.0 years) performed isometric muscle actions of the leg extensors at 10-100% of their maximal voluntary contraction on two separate occasions. One trial was performed inside a Faraday tent (a flexible Faraday cage made from conductive material), and the other was performed outside the Faraday tent. The EMG signals collected outside the Faraday tent were analyzed three separate ways: as a raw signal, as a bipolar signal, and as a signal digitally notch filtered to remove 60 Hz noise and its harmonics. The signal-to-noise ratios were greatest after notch-filtering (range: 3.0-33.8), and lowest for the bipolar arrangement (1.6-10.2). Linear slope coefficients for the EMG amplitude versus force relationship were also used to compare the methods of noise removal. The results showed that a bipolar arrangement had a significantly lower linear slope coefficient when compared to the three other conditions (raw, notch and tent). These results suggested that an appropriately filtered monopolar EMG signal can be useful in situations that require a large pick-up area. Furthermore, although it is helpful, a Faraday tent (or cage) is not required to achieve an appropriate signal-to-noise ratio, as long as the correct filters are applied.

Comparison of methods for removing electromagnetic noise from electromyographic signals

International Nuclear Information System (INIS)

DeFreitas, Jason M; Beck, Travis W; Stock, Matt S

2012-01-01

The purpose of this investigation was to compare three different methods of removing noise from monopolar electromyographic (EMG) signals: (a) electrical shielding with a Faraday cage, (b) denoising with a digital notch-filter and (c) applying a bipolar differentiation with another monopolar EMG signal. Ten men and ten women (mean age = 24.0 years) performed isometric muscle actions of the leg extensors at 10–100% of their maximal voluntary contraction on two separate occasions. One trial was performed inside a Faraday tent (a flexible Faraday cage made from conductive material), and the other was performed outside the Faraday tent. The EMG signals collected outside the Faraday tent were analyzed three separate ways: as a raw signal, as a bipolar signal, and as a signal digitally notch filtered to remove 60 Hz noise and its harmonics. The signal-to-noise ratios were greatest after notch-filtering (range: 3.0–33.8), and lowest for the bipolar arrangement (1.6–10.2). Linear slope coefficients for the EMG amplitude versus force relationship were also used to compare the methods of noise removal. The results showed that a bipolar arrangement had a significantly lower linear slope coefficient when compared to the three other conditions (raw, notch and tent). These results suggested that an appropriately filtered monopolar EMG signal can be useful in situations that require a large pick-up area. Furthermore, although it is helpful, a Faraday tent (or cage) is not required to achieve an appropriate signal-to-noise ratio, as long as the correct filters are applied. (paper)

Properties of Bipolar Fuzzy Hypergraphs

OpenAIRE

Akram, M.; Dudek, W. A.; Sarwar, S.

2013-01-01

In this article, we apply the concept of bipolar fuzzy sets to hypergraphs and investigate some properties of bipolar fuzzy hypergraphs. We introduce the notion of $A-$ tempered bipolar fuzzy hypergraphs and present some of their properties. We also present application examples of bipolar fuzzy hypergraphs.

Development of a large scale bipolar NiH2 battery

Science.gov (United States)

Adler, E.; Perez, F.

1983-01-01

The bipolar battery concept, developed in cooperation with NASA, is described in the context of the advantages afforded by near-term IPV and CVP cell technology. The projected performance, development requirements, and a possible approach to bipolar battery design are outlined. Consideration is given to packaging electrodes within a common hydrophobic plastic frame, electrode technology that involves a photochemically etched 0.1 mm thick nickel substrate coated with a 10 mg/sq cm mixture of platinum powder and TFE30, and an electrode design that eliminates the screen and doubles the electrode thickness (from the currently used 0.8 mm) while retaining the active material loading of 1.6-1.8 gm/cu cm. Also covered are thermal management, and electrolyte and oxygen management. It is concluded that a high voltage, high capacity, bipolar NiH2 cell can be configured with proper development for use in large power systems, and that it can provide considerable weight savings.

Bipolar Affective Disorder and Migraine

Directory of Open Access Journals (Sweden)

Birk Engmann

2012-01-01

Full Text Available This paper consists of a case history and an overview of the relationship, aetiology, and treatment of comorbid bipolar disorder migraine patients. A MEDLINE literature search was used. Terms for the search were bipolar disorder bipolar depression, mania, migraine, mood stabilizer. Bipolar disorder and migraine cooccur at a relatively high rate. Bipolar II patients seem to have a higher risk of comorbid migraine than bipolar I patients have. The literature on the common roots of migraine and bipolar disorder, including both genetic and neuropathological approaches, is broadly discussed. Moreover, bipolar disorder and migraine are often combined with a variety of other affective disorders, and, furthermore, behavioural factors also play a role in the origin and course of the diseases. Approach to treatment options is also difficult. Several papers point out possible remedies, for example, valproate, topiramate, which acts on both diseases, but no first-choice treatments have been agreed upon yet.

Presynaptic dystroglycan-pikachurin complex regulates the proper synaptic connection between retinal photoreceptor and bipolar cells.

Science.gov (United States)

Omori, Yoshihiro; Araki, Fumiyuki; Chaya, Taro; Kajimura, Naoko; Irie, Shoichi; Terada, Koji; Muranishi, Yuki; Tsujii, Toshinori; Ueno, Shinji; Koyasu, Toshiyuki; Tamaki, Yasuhiro; Kondo, Mineo; Amano, Shiro; Furukawa, Takahisa

2012-05-02

Dystroglycan (DG) is a key component of the dystrophin-glycoprotein complex (DGC) at the neuromuscular junction postsynapse. In the mouse retina, the DGC is localized at the presynapse of photoreceptor cells, however, the function of presynaptic DGC is poorly understood. Here, we developed and analyzed retinal photoreceptor-specific DG conditional knock-out (DG CKO) mice. We found that the DG CKO retina showed a reduced amplitude and a prolonged implicit time of the ERG b-wave. Electron microscopic analysis revealed that bipolar dendrite invagination into the photoreceptor terminus is perturbed in the DG CKO retina. In the DG CKO retina, pikachurin, a DG ligand in the retina, is markedly decreased at photoreceptor synapses. Interestingly, in the Pikachurin(-/-) retina, the DG signal at the ribbon synaptic terminus was severely reduced, suggesting that pikachurin is required for the presynaptic accumulation of DG at the photoreceptor synaptic terminus, and conversely DG is required for pikachurin accumulation. Furthermore, we found that overexpression of pikachurin induces formation and clustering of a DG-pikachurin complex on the cell surface. The Laminin G repeats of pikachurin, which are critical for its oligomerization and interaction with DG, were essential for the clustering of the DG-pikachurin complex as well. These results suggest that oligomerization of pikachurin and its interaction with DG causes DG assembly on the synapse surface of the photoreceptor synaptic terminals. Our results reveal that the presynaptic interaction of pikachurin with DG at photoreceptor terminals is essential for both the formation of proper photoreceptor ribbon synaptic structures and normal retinal electrophysiology.

Bipolar Disorder in Children

Science.gov (United States)

2014-01-01

Although bipolar disorder historically was thought to only occur rarely in children and adolescents, there has been a significant increase in children and adolescents who are receiving this diagnosis more recently (Carlson, 2005). Nonetheless, the applicability of the current bipolar disorder diagnostic criteria for children, particularly preschool children, remains unclear, even though much work has been focused on this area. As a result, more work needs to be done to further the understanding of bipolar symptoms in children. It is hoped that this paper can assist psychologists and other health service providers in gleaning a snapshot of the literature in this area so that they can gain an understanding of the diagnostic criteria and other behaviors that may be relevant and be informed about potential approaches for assessment and treatment with children who meet bipolar disorder criteria. First, the history of bipolar symptoms and current diagnostic criteria will be discussed. Next, assessment strategies that may prove helpful for identifying bipolar disorder will be discussed. Then, treatments that may have relevance to children and their families will be discussed. Finally, conclusions regarding work with children who may have a bipolar disorder diagnosis will be offered. PMID:24800202

Cytokines in bipolar disorder

DEFF Research Database (Denmark)

Munkholm, Klaus; Vinberg, Maj; Vedel Kessing, Lars

2012-01-01

BACKGROUND: Current research and hypothesis regarding the pathophysiology of bipolar disorder suggests the involvement of immune system dysfunction that is possibly related to disease activity. Our objective was to systematically review evidence of cytokine alterations in bipolar disorder according...... to affective state. METHODS: We conducted a systemtic review of studies measuring endogenous cytokine concentrations in patients with bipolar disorder and a meta-analysis, reporting results according to the PRISMA statement. RESULTS: Thirteen studies were included, comprising 556 bipolar disorder patients...

Determinants of cell-to-cell variability in protein kinase signaling.

Science.gov (United States)

Jeschke, Matthias; Baumgärtner, Stephan; Legewie, Stefan

2013-01-01

Cells reliably sense environmental changes despite internal and external fluctuations, but the mechanisms underlying robustness remain unclear. We analyzed how fluctuations in signaling protein concentrations give rise to cell-to-cell variability in protein kinase signaling using analytical theory and numerical simulations. We characterized the dose-response behavior of signaling cascades by calculating the stimulus level at which a pathway responds ('pathway sensitivity') and the maximal activation level upon strong stimulation. Minimal kinase cascades with gradual dose-response behavior show strong variability, because the pathway sensitivity and the maximal activation level cannot be simultaneously invariant. Negative feedback regulation resolves this trade-off and coordinately reduces fluctuations in the pathway sensitivity and maximal activation. Feedbacks acting at different levels in the cascade control different aspects of the dose-response curve, thereby synergistically reducing the variability. We also investigated more complex, ultrasensitive signaling cascades capable of switch-like decision making, and found that these can be inherently robust to protein concentration fluctuations. We describe how the cell-to-cell variability of ultrasensitive signaling systems can be actively regulated, e.g., by altering the expression of phosphatase(s) or by feedback/feedforward loops. Our calculations reveal that slow transcriptional negative feedback loops allow for variability suppression while maintaining switch-like decision making. Taken together, we describe design principles of signaling cascades that promote robustness. Our results may explain why certain signaling cascades like the yeast pheromone pathway show switch-like decision making with little cell-to-cell variability.

Abordagens psicoterápicas no transtorno bipolar Psychoterapeutic approach in bipolar disorder

Directory of Open Access Journals (Sweden)

Paulo Knapp

2005-01-01

Full Text Available Embora o tratamento farmacológico seja essencial para o tratamento do transtorno bipolar, apenas 40% de todos os pacientes que aderem às medicações permanecem assintomáticos durante o período de seguimento, o que tem levado ao desenvolvimento de intervenções psicoterápicas associadas. O objetivo deste artigo é examinar as evidências atuais da eficácia de intervenções psicoterápicas no tratamento do transtorno bipolar. Foi realizada uma pesquisa bibliográfica por meio do MedLine, PsychoINFO, Lilacs e Cochrane Data Bank, até o ano de 2004, em que foram procurados artigos originais e revisões sobre as abordagens psicoterápicas utilizadas no tratamento do transtorno bipolar. Há várias abordagens que podem se mostrar úteis no tratamento do transtorno bipolar. A psicoeducação e a terapia cognitivo-comportamental apresentam as evidências mais consistentes e são as técnicas mais amplamente estudadas. As intervenções envolvendo familiares e a terapia interpessoal e de ritmo social se mostram tratamentos eficazes em determinadas situações. Há alguns estudos empregando a terapia psicodinâmica no transtorno bipolar, mas são estudos com limitações metodológicas. Apesar de haver evidências demonstrando a eficácia de determinadas abordagens psicoterápicas no transtorno bipolar, ainda é necessária a realização de estudos posteriores que comprovem tais dados e que desenvolvam tratamentos baseados em modelos etiológicos e que identifiquem tratamentos específicos para as diferentes fases e tipos de transtorno bipolar.Although pharmacological treatment is essential for treating bipolar disorder, less than half of all medication compliant patients are non-symptomatic during follow-up, which has led to developments of adjunctive psychosocial interventions. This paper examines the current evidence for effectiveness of psychotherapeutic interventions in the treatment of bipolar disorder. Searches were undertaken through Med

ON BIPOLAR SINGLE VALUED NEUTROSOPHIC GRAPHS

OpenAIRE

Said Broumi; Mohamed Talea; Assia Bakali; Florentin Smarandache

2016-01-01

In this article, we combine the concept of bipolar neutrosophic set and graph theory. We introduce the notions of bipolar single valued neutrosophic graphs, strong bipolar single valued neutrosophic graphs, complete bipolar single valued neutrosophic graphs, regular bipolar single valued neutrosophic graphs and investigate some of their related properties.

CT-guided Bipolar and Multipolar Radiofrequency Ablation (RF Ablation) of Renal Cell Carcinoma: Specific Technical Aspects and Clinical Results

Energy Technology Data Exchange (ETDEWEB)

Sommer, C. M., E-mail: christof.sommer@med.uni-heidelberg.de [University Hospital Heidelberg, INF 110, Department of Diagnostic and Interventional Radiology (Germany); Lemm, G.; Hohenstein, E. [Minimally Invasive Therapies and Nuclear Medicine, SLK Kliniken Heilbronn GmbH, Clinic for Radiology (Germany); Bellemann, N.; Stampfl, U. [University Hospital Heidelberg, INF 110, Department of Diagnostic and Interventional Radiology (Germany); Goezen, A. S.; Rassweiler, J. [Clinic for Urology, SLK Kliniken Heilbronn GmbH (Germany); Kauczor, H. U.; Radeleff, B. A. [University Hospital Heidelberg, INF 110, Department of Diagnostic and Interventional Radiology (Germany); Pereira, P. L. [Minimally Invasive Therapies and Nuclear Medicine, SLK Kliniken Heilbronn GmbH, Clinic for Radiology (Germany)

2013-06-15

Purpose. This study was designed to evaluate the clinical efficacy of CT-guided bipolar and multipolar radiofrequency ablation (RF ablation) of renal cell carcinoma (RCC) and to analyze specific technical aspects between both technologies. Methods. We included 22 consecutive patients (3 women; age 74.2 {+-} 8.6 years) after 28 CT-guided bipolar or multipolar RF ablations of 28 RCCs (diameter 2.5 {+-} 0.8 cm). Procedures were performed with a commercially available RF system (Celon AG Olympus, Berlin, Germany). Technical aspects of RF ablation procedures (ablation mode [bipolar or multipolar], number of applicators and ablation cycles, overall ablation time and deployed energy, and technical success rate) were analyzed. Clinical results (local recurrence-free survival and local tumor control rate, renal function [glomerular filtration rate (GFR)]) and complication rates were evaluated. Results. Bipolar RF ablation was performed in 12 procedures and multipolar RF ablation in 16 procedures (2 applicators in 14 procedures and 3 applicators in 2 procedures). One ablation cycle was performed in 15 procedures and two ablation cycles in 13 procedures. Overall ablation time and deployed energy were 35.0 {+-} 13.6 min and 43.7 {+-} 17.9 kJ. Technical success rate was 100 %. Major and minor complication rates were 4 and 14 %. At an imaging follow-up of 15.2 {+-} 8.8 months, local recurrence-free survival was 14.4 {+-} 8.8 months and local tumor control rate was 93 %. GFR did not deteriorate after RF ablation (50.8 {+-} 16.6 ml/min/1.73 m{sup 2} before RF ablation vs. 47.2 {+-} 11.9 ml/min/1.73 m{sup 2} after RF ablation; not significant). Conclusions. CT-guided bipolar and multipolar RF ablation of RCC has a high rate of clinical success and low complication rates. At short-term follow-up, clinical efficacy is high without deterioration of the renal function.

Systematic review of the prevalence of bipolar disorder and bipolar spectrum disorders in population-based studies

Directory of Open Access Journals (Sweden)

José Caetano Dell'Aglio Jr.

2013-01-01

Full Text Available This paper describes the findings of a systematic literature review aimed at providing an overview of the lifetime prevalence of bipolar disorder and bipolar spectrum disorders in population-based studies. Databases MEDLINE, ProQuest, Psychnet, and Web of Science were browsed for papers published in English between 1999 and May 2012 using the following search string: bipolar disorders OR bipolar spectrum disorders AND prevalence OR cross-sectional OR epidemiology AND population-based OR non-clinical OR community based. The search yielded a total of 434 papers, but only those published in peer-reviewed journals and with samples aged ≥ 18 years were included, resulting in a final sample of 18 papers. Results revealed rather heterogeneous findings concerning the prevalence of bipolar disorders and bipolar spectrum disorders. Lifetime prevalence of bipolar disorder ranged from 0.1 to 7.5%, whereas lifetime prevalence of bipolar spectrum disorders ranged from 2.4 to 15.1%. Differences in the rates of bipolar disorder and bipolar spectrum disorders may be related to the consideration of subthreshold criteria upon diagnosis. Differences in the prevalence of different subtypes of the disorder are discussed in light of diagnostic criteria and instruments applied.

Psychosis and relapse in bipolar disorder are related to GRM3 ...

African Journals Online (AJOL)

; mGluR3; G72 protein; HumanDysfunction in glutamate signalling is thought to play a role in the pathophysiology of bipolar disorder (BD). There is evidence of associations between single nucleotide polymorphisms (SNPs) in GRM3, GRIN2B, ...

Scientific attitudes towards bipolar disorders

Directory of Open Access Journals (Sweden)

Mohammad-Hossein Biglu

2014-02-01

Full Text Available Introduction: Bipolar disorder is a psychiatric condition that is also called manic-depressive disease. It causes unusual changes in mood, energy, activity levels, and the ability to carry out day-to-day tasks. In the present study, 3 sets of data were considered and analyzed: first, all papers categorized under Bipolar Disorders in Science Citation Index Expanded (SCI-E database through 2001-2011; second, papers published by the international journal of Bipolar Disorders indexed in SCI-E during a period of 11 years; and third, all papers distributed by the international journal of Bipolar Disorders indexed in MEDLINE during the period of study. Methods: The SCI-E database was used to extract all papers indexed with the topic of Bipolar Disorders as well as all papers published by The International Journal of Bipolar Disorders. Extraction of data from MEDLINE was restricted to the journals name from setting menu. The Science of Science Tool was used to map the co-authorship network of papers published by The International Journal of Bipolar Disorders through 2009-2011. Results: Analysis of data showed that the majority of publications in the subject area of bipolar disorders indexed in SCI-E were published by The International Journal of Bipolar Disorders. Although journal articles consisted of 59% of the total publication type in SCI-E, 65% of publications distributed by The Journal of Bipolar Disorders were in the form of meetingabstracts. Journal articles consisted of only 23% of the total publications. USA was the leading country regarding sharing data in the field of bipolar disorders followed by England, Canada, and Germany. Conclusion: The editorial policy of The International Journal of Bipolar Disorders has been focused on new themes and new ways of researching in the subject area of bipolar disorder. Regarding the selection of papers for indexing, the SCI-E database selects data more comprehensively than MEDLINE. The number of papers

Bipolar Disorder.

Science.gov (United States)

Spearing, Melissa

Bipolar disorder, a brain disorder that causes unusual shifts in a person's mood, affects approximately one percent of the population. It commonly occurs in late adolescence and is often unrecognized. The diagnosis of bipolar disorder is made on the basis of symptoms, course of illness, and when possible, family history. Thoughts of suicide are…

N-Acetylglucosamine Functions in Cell Signaling

Directory of Open Access Journals (Sweden)

James B. Konopka

2012-01-01

Full Text Available The amino sugar N-acetylglucosamine (GlcNAc is well known for the important structural roles that it plays at the cell surface. It is a key component of bacterial cell wall peptidoglycan, fungal cell wall chitin, and the extracellular matrix of animal cells. Interestingly, recent studies have also identified new roles for GlcNAc in cell signaling. For example, GlcNAc stimulates the human fungal pathogen Candida albicans to undergo changes in morphogenesis and expression of virulence genes. Pathogenic E. coli responds to GlcNAc by altering the expression of fimbriae and CURLI fibers that promote biofilm formation and GlcNAc stimulates soil bacteria to undergo changes in morphogenesis and production of antibiotics. Studies with animal cells have revealed that GlcNAc influences cell signaling through the posttranslational modification of proteins by glycosylation. O-linked attachment of GlcNAc to Ser and Thr residues regulates a variety of intracellular proteins, including transcription factors such as NFκB, c-myc, and p53. In addition, the specificity of Notch family receptors for different ligands is altered by GlcNAc attachment to fucose residues in the extracellular domain. GlcNAc also impacts signal transduction by altering the degree of branching of N-linked glycans, which influences cell surface signaling proteins. These emerging roles of GlcNAc as an activator and mediator of cellular signaling in fungi, animals, and bacteria will be the focus of this paper.

Determinants of cell-to-cell variability in protein kinase signaling.

Directory of Open Access Journals (Sweden)

Matthias Jeschke

Full Text Available Cells reliably sense environmental changes despite internal and external fluctuations, but the mechanisms underlying robustness remain unclear. We analyzed how fluctuations in signaling protein concentrations give rise to cell-to-cell variability in protein kinase signaling using analytical theory and numerical simulations. We characterized the dose-response behavior of signaling cascades by calculating the stimulus level at which a pathway responds ('pathway sensitivity' and the maximal activation level upon strong stimulation. Minimal kinase cascades with gradual dose-response behavior show strong variability, because the pathway sensitivity and the maximal activation level cannot be simultaneously invariant. Negative feedback regulation resolves this trade-off and coordinately reduces fluctuations in the pathway sensitivity and maximal activation. Feedbacks acting at different levels in the cascade control different aspects of the dose-response curve, thereby synergistically reducing the variability. We also investigated more complex, ultrasensitive signaling cascades capable of switch-like decision making, and found that these can be inherently robust to protein concentration fluctuations. We describe how the cell-to-cell variability of ultrasensitive signaling systems can be actively regulated, e.g., by altering the expression of phosphatase(s or by feedback/feedforward loops. Our calculations reveal that slow transcriptional negative feedback loops allow for variability suppression while maintaining switch-like decision making. Taken together, we describe design principles of signaling cascades that promote robustness. Our results may explain why certain signaling cascades like the yeast pheromone pathway show switch-like decision making with little cell-to-cell variability.

High-gain bipolar detector on float-zone silicon

Science.gov (United States)

Han, D. J.; Batignani, G.; Del Guerra, A.; Dalla Betta, G.-F.; Boscardin, M.; Bosisio, L.; Giorgi, M.; Forti, F.

2003-10-01

Since the float-zone (FZ) silicon has lower contaminations and longer minority-carrier lifetime than those in Czochralski silicon and other semiconductor materials, it has potential advantages to fabricate bipolar detectors on the high-purity FZ silicon substrate to achieve a high gain at ultra-low-signal levels. The authors present preliminary experimental results on a bipolar detector fabricated on an unusual high-purity FZ silicon substrate. A backside gettering layer of phosphorus-doped polysilicon was employed to preserve the long carrier lifetime of the high-purity FZ silicon. The device has been investigated in the detection of a continuous flux of X-ray and infrared light. The bipolar detector with a circular emitter of 2 mm diameter has demonstrated high gains up to 3820 for 22 keV X-ray from a 1 mCi Cd radioactive source (the X-ray photon flux, received by the detector is estimated to be ˜7.77×10 4/s). High gain up to 4400 for 0.17 nW light with a wavelength of 0.83 μm has been observed for the same device.

High-gain bipolar detector on float-zone silicon

International Nuclear Information System (INIS)

Han, D.J.; Batignani, G.; Guerra, A.D.A. Del; Dalla Betta, G.-F.; Boscardin, M.; Bosisio, L.; Giorgi, M.; Forti, F.

2003-01-01

Since the float-zone (FZ) silicon has lower contaminations and longer minority-carrier lifetime than those in Czochralski silicon and other semiconductor materials, it has potential advantages to fabricate bipolar detectors on the high-purity FZ silicon substrate to achieve a high gain at ultra-low-signal levels. The authors present preliminary experimental results on a bipolar detector fabricated on an unusual high-purity FZ silicon substrate. A backside gettering layer of phosphorus-doped polysilicon was employed to preserve the long carrier lifetime of the high-purity FZ silicon. The device has been investigated in the detection of a continuous flux of X-ray and infrared light. The bipolar detector with a circular emitter of 2 mm diameter has demonstrated high gains up to 3820 for 22 keV X-ray from a 1 mCi Cd radioactive source (the X-ray photon flux, received by the detector is estimated to be ∼7.77x10 4 /s). High gain up to 4400 for 0.17 nW light with a wavelength of 0.83 μm has been observed for the same device

Lipid rafts and B cell signaling.

Science.gov (United States)

Gupta, Neetu; DeFranco, Anthony L

2007-10-01

B cells comprise an essential component of the humoral immune system. They are equipped with the unique ability to synthesize and secrete pathogen-neutralizing antibodies, and share with professional antigen presenting cells the ability to internalize foreign antigens, and process them for presentation to helper T cells. Recent evidence indicates that specialized cholesterol- and glycosphingolipid-rich microdomains in the plasma membrane commonly referred to as lipid rafts, serve to compartmentalize key signaling molecules during the different stages of B cell activation including B cell antigen receptor (BCR)-initiated signal transduction, endocytosis of BCR-antigen complexes, loading of antigenic peptides onto MHC class II molecules, MHC-II associated antigen presentation to helper T cells, and receipt of helper signals via the CD40 receptor. Here we review the recent literature arguing for a role of lipid rafts in the spatial organization of B cell function.

Thwarted interpersonal needs and suicide ideation: Comparing psychiatric inpatients with bipolar and non-bipolar mood disorders.

Science.gov (United States)

Taylor, Nathanael J; Mitchell, Sean M; Roush, Jared F; Brown, Sarah L; Jahn, Danielle R; Cukrowicz, Kelly C

2016-12-30

Psychiatric inpatients are at heightened risk for suicide, and evidence suggests that psychiatric inpatients with bipolar mood disorders may be at greater risk for suicide ideation compared to those with non-bipolar mood disorders. There is a paucity of research directly comparing risk factors for suicide ideation in bipolar versus non-bipolar mood disorders in an inpatient sample. The current study sought to clarify the association between two constructs from the interpersonal theory of suicide (i.e., perceived burdensomeness and thwarted belongingness) in leading to suicide ideation among psychiatric inpatients with bipolar and non-bipolar mood disorders. Participants were (N=90) psychiatric inpatients with a bipolar (n = 20) or non-bipolar mood disorder (n=70; per their medical charts). Perceived burdensomeness, but not thwarted belongingness, was significantly associated with suicide ideation after adjusting for other covariates. This suggests perceived burdensomeness may play a key role in suicide ideation among psychiatric inpatients with any mood disorder and highlights the importance of assessment and intervention of perceived burdensomeness in this population. Contrary to our hypothesis, mood disorder group (i.e., bipolar versus non-bipolar) did not moderate the relations between perceived burdensomeness/thwarted belongingness and suicide ideation. Published by Elsevier Ireland Ltd.

Bipolar polygenic loading and bipolar spectrum features in major depressive disorder

Science.gov (United States)

Wiste, Anna; Robinson, Elise B; Milaneschi, Yuri; Meier, Sandra; Ripke, Stephan; Clements, Caitlin C; Fitzmaurice, Garrett M; Rietschel, Marcella; Penninx, Brenda W; Smoller, Jordan W; Perlis, Roy H

2014-01-01

Objectives Family and genetic studies indicate overlapping liability for major depressive disorder and bipolar disorder. The purpose of this study was to determine whether this shared genetic liability influences clinical presentation. Methods A polygenic risk score for bipolar disorder, derived from a large genome-wide association meta-analysis, was generated for each subject of European–American ancestry (n = 1,274) in the Sequential Treatment Alternatives to Relieve Depression study (STAR*D) outpatient major depressive disorder cohort. A hypothesis-driven approach was used to test for association between bipolar disorder risk score and features of depression associated with bipolar disorder in the literature. Follow-up analyses were performed in two additional cohorts. Results A generalized linear mixed model including seven features hypothesized to be associated with bipolar spectrum illness was significantly associated with bipolar polygenic risk score [F = 2.07, degrees of freedom (df) = 7, p = 0.04). Features included early onset, suicide attempt, recurrent depression, atypical depression, subclinical mania, subclinical psychosis, and severity. Post-hoc univariate analyses demonstrated that the major contributors to this omnibus association were onset of illness at age ≤ 18 years [odds ratio (OR) = 1.2, p = 0.003], history of suicide attempt (OR = 1.21, p = 0.03), and presence of at least one manic symptom (OR = 1.16, p = 0.02). The maximal variance in these traits explained by polygenic score ranged from 0.8–1.1%. However, analyses in two replication cohorts testing a five feature model did not support this association. Conclusions Bipolar genetic loading appeared to be associated with bipolar-like presentation in major depressive disorder in the primary analysis. However, results are at most inconclusive because of lack of replication. Replication efforts are challenged by different ascertainment and assessment strategies in the different cohorts

Development of a portable PEM fuel cell system with bipolar plates consisting an electronically conductive thermoplastic Compound material; Entwicklung eines portablen PEM-Brennstoffzellensystems mit Bipolarplatten aus einem elektronisch leitfaehigen thermoplastischen Compound-Material

Energy Technology Data Exchange (ETDEWEB)

Niemzig, O.C.

2005-07-18

In order to meet the cost targets of PEM fuel cells for commercialization significant cost reductions of cell stack components like membrane/electrode assemblies and bipolar plates have become key aspects of research and development. Central topics of his work are the bipolar plates and humidification for portable applications. Best results concerning conductivity of an extensive screening of a variety of carbon polymer compounds with polypropylene as matrix could be achieved with the carbon black/graphite/polypropylene-base system. Successful tests of this material in a fuel cell stack could be performed as well as the proof of suitability concerning material- and manufacturing costs. Dependent on application a decrease of material cost to 2 Euro/kg to 1,8 Euro/kW seems to be possible. Finally bipolar plates consisting of a selected carbon polymer compound were successfully integrated and tested in a 20-cell stack which was implemented in a portable PEFC-demonstrator unit with a power output between 50 and 150 W. (orig.)

Daily electronic self-monitoring of subjective and objective symptoms in bipolar disorder—the MONARCA trial protocol (MONitoring, treAtment and pRediCtion of bipolAr disorder episodes)

DEFF Research Database (Denmark)

Faurholt-Jepsen, Maria; Vinberg, Maj; Christensen, Ellen Margrethe

2013-01-01

Electronic self-monitoring of affective symptoms using cell phones is suggested as a practical and inexpensive way to monitor illness activity and identify early signs of affective symptoms. It has never been tested in a randomised clinical trial whether electronic self-monitoring improves outcomes...... in bipolar disorder. We are conducting a trial testing the effect of using a Smartphone for self-monitoring in bipolar disorder....

Genetics Home Reference: bipolar disorder

Science.gov (United States)

... Email Facebook Twitter Home Health Conditions Bipolar disorder Bipolar disorder Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Bipolar disorder is a mental health condition that causes extreme ...

Coupling Planar Cell Polarity Signaling to Morphogenesis

Directory of Open Access Journals (Sweden)

Jeffrey D. Axelrod

2002-01-01

Full Text Available Epithelial cells and other groups of cells acquire a polarity orthogonal to their apical–basal axes, referred to as Planar Cell Polarity (PCP. The process by which these cells become polarized requires a signaling pathway using Frizzled as a receptor. Responding cells sense cues from their environment that provide directional information, and they translate this information into cellular asymmetry. Most of what is known about PCP derives from studies in the fruit fly, Drosophila. We review what is known about how cells translate an unknown signal into asymmetric cytoskeletal reorganization. We then discuss how the vertebrate processes of convergent extension and cochlear hair-cell development may relate to Drosophila PCP signaling.

A Narrow and Highly Significant Linkage Signal for Severe Bipolar Disorder in the Chromosome 5q33 Region in Latin American Pedigrees

Science.gov (United States)

Jasinska, A.J.; Service, S.; Jawaheer, D.; DeYoung, J.; Levinson, M.; Zhang, Z.; Kremeyer, B.; Muller, H.; Aldana, I.; Garcia, J.; Restrepo, G.; Lopez, C.; Palacio, C.; Duque, C.; Parra, M.; Vega, J.; Ortiz, D.; Bedoya, G.; Mathews, C.; Davanzo, P.; Fournier, E.; Bejarano, J.; Ramirez, M.; Ortiz, C. Araya; Araya, X.; Molina, J.; Sabatti, C.; Reus, V.; Ospina, J.; Macaya, G.; Ruiz-Linares, A.; Freimer, N.B.

2016-01-01

We previously reported linkage of bipolar disorder to 5q33-q34 in families from two closely related population isolates, the Central Valley of Costa Rica (CVCR) and Antioquia, Colombia (CO). Here we present follow up results from fine-scale mapping in large CVCR and CO families segregating severe bipolar disorder, BP-I, and in 343 population trios/duos from CVCR and CO. Employing densely spaced SNPs to fine map the prior linkage peak region increases linkage evidence and clarifies the position of the putative BP-I locus. We performed two-point linkage analysis with 1134 SNPs in an approximately 9 Mb region between markers D5S410 and D5S422. Combining pedigrees from CVCR and CO yields a LOD score of 4.9 at SNP rs10035961. Two other SNPs (rs7721142 and rs1422795) within the same 94 kb region also displayed LOD scores greater than 4. This linkage peak coincides with our prior microsatellite results and suggests a narrowed BP-I susceptibility regions in these families. To investigate if the locus implicated in the familial form of BP-I also contributes to disease risk in the population, we followed up the family results with association analysis in duo and trio samples, obtaining signals within 2 Mb of the peak linkage signal in the pedigrees; rs12523547 and rs267015 (P = 0.00004 and 0.00016, respectively) in the CO sample and rs244960 in the CVCR sample and the combined sample, with P = 0.00032 and 0.00016, respectively. It remains unclear whether these association results reflect the same locus contributing to BP susceptibility within the extended pedigrees. PMID:19319892

Bipolar nickel-hydrogen battery design

Science.gov (United States)

Koehler, C. W.; Applewhite, A. Z.; Kuo, Y.

1985-01-01

The initial design for the NASA-Lewis advanced nickel-hydrogen battery is discussed. Fabrication of two 10-cell boilerplate battery stacks will soon begin. The test batteries will undergo characterization testing and low Earth orbit life cycling. The design effectively deals with waste heat generated in the cell stack. Stack temperatures and temperature gradients are maintained to acceptable limits by utilizing the bipolar conduction plate as a heat path to the active cooling fluid panel external to the edge of the cell stack. The thermal design and mechanical design of the battery stack together maintain a materials balance within the cell. An electrolyte seal on each cell frame prohibits electrolyte bridging. An oxygen recombination site and electrolyte reservoir/separator design does not allow oxygen to leave the cell in which it was generated.

Life expectancy in bipolar disorder

DEFF Research Database (Denmark)

Kessing, Lars Vedel; Vradi, Eleni; Andersen, Per Kragh

2015-01-01

OBJECTIVE: Life expectancy in patients with bipolar disorder has been reported to be decreased by 11 to 20 years. These calculations are based on data for individuals at the age of 15 years. However, this may be misleading for patients with bipolar disorder in general as most patients have a later...... onset of illness. The aim of the present study was to calculate the remaining life expectancy for patients of different ages with a diagnosis of bipolar disorder. METHODS: Using nationwide registers of all inpatient and outpatient contacts to all psychiatric hospitals in Denmark from 1970 to 2012 we...... remaining life expectancy in bipolar disorder and that of the general population decreased with age, indicating that patients with bipolar disorder start losing life-years during early and mid-adulthood. CONCLUSIONS: Life expectancy in bipolar disorder is decreased substantially, but less so than previously...

Distinct lithium-induced gene expression effects in lymphoblastoid cell lines from patients with bipolar disorder.

Science.gov (United States)

Fries, Gabriel R; Colpo, Gabriela D; Monroy-Jaramillo, Nancy; Zhao, Junfei; Zhao, Zhongming; Arnold, Jodi G; Bowden, Charles L; Walss-Bass, Consuelo

2017-11-01

Lithium is the most commonly prescribed medication for the treatment of bipolar disorder (BD), yet the mechanisms underlying its beneficial effects are still unclear. We aimed to compare the effects of lithium treatment in lymphoblastoid cell lines (LCLs) from BD patients and controls. LCLs were generated from sixty-two BD patients (based on DSM-IV) and seventeen healthy controls matched for age, sex, and ethnicity. Patients were recruited from outpatient clinics from February 2012 to October 2014. LCLs were treated with 1mM lithium for 7 days followed by microarray gene expression assay and validation by real-time quantitative PCR. Baseline differences between groups, as well as differences between vehicle- and lithium-treated cells within each group were analyzed. The biological significance of differentially expressed genes was examined by pathway enrichment analysis. No significant differences in baseline gene expression (adjusted p-value < 0.05) were detected between groups. Lithium treatment of LCLs from controls did not lead to any significant differences. However, lithium altered the expression of 236 genes in LCLs from patients; those genes were enriched for signaling pathways related to apoptosis. Among those genes, the alterations in the expression of PIK3CG, SERP1 and UPP1 were validated by real-time PCR. A significant correlation was also found between circadian functioning and CEBPG and FGF2 expression levels. In summary, our results suggest that lithium treatment induces expression changes in genes associated with the apoptosis pathway in BD LCLs. The more pronounced effects of lithium in patients compared to controls suggest a disease-specific effect of this drug. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.

Bipolar Disorder in Women

Directory of Open Access Journals (Sweden)

Sermin Kesebir

2013-06-01

Full Text Available The research on gender's role in bipolar disorders has drawn significant interest recently. The presentation and course of bipolar disorder differs between women and men. Women experience depressive episodes, dysphoric mood, mixed states, rapid cycling and seasonal patterns more often than men. Comorbidity, particularly thyroid disease, migraine, obesity, and anxiety disorders laso occur more frequently in women than men. On the other hand men with bipolar disorder are also more likely than women to have problems with drug or alcohol abuse. The pregnancy and postpartum period is a time of high risk for onset and recurrence of bipolar disorder in women.

Decoding Signal Processing at the Single-Cell Level

Energy Technology Data Exchange (ETDEWEB)

Wiley, H. Steven

2017-12-01

The ability of cells to detect and decode information about their extracellular environment is critical to generating an appropriate response. In multicellular organisms, cells must decode dozens of signals from their neighbors and extracellular matrix to maintain tissue homeostasis while still responding to environmental stressors. How cells detect and process information from their surroundings through a surprisingly limited number of signal transduction pathways is one of the most important question in biology. Despite many decades of research, many of the fundamental principles that underlie cell signal processing remain obscure. However, in this issue of Cell Systems, Gillies et al present compelling evidence that the early response gene circuit can act as a linear signal integrator, thus providing significant insight into how cells handle fluctuating signals and noise in their environment.

Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4.

LENUS (Irish Health Repository)

Sklar, Pamela

2011-10-01

We conducted a combined genome-wide association study (GWAS) of 7,481 individuals with bipolar disorder (cases) and 9,250 controls as part of the Psychiatric GWAS Consortium. Our replication study tested 34 SNPs in 4,496 independent cases with bipolar disorder and 42,422 independent controls and found that 18 of 34 SNPs had P < 0.05, with 31 of 34 SNPs having signals with the same direction of effect (P = 3.8 × 10(-7)). An analysis of all 11,974 bipolar disorder cases and 51,792 controls confirmed genome-wide significant evidence of association for CACNA1C and identified a new intronic variant in ODZ4. We identified a pathway comprised of subunits of calcium channels enriched in bipolar disorder association intervals. Finally, a combined GWAS analysis of schizophrenia and bipolar disorder yielded strong association evidence for SNPs in CACNA1C and in the region of NEK4-ITIH1-ITIH3-ITIH4. Our replication results imply that increasing sample sizes in bipolar disorder will confirm many additional loci.

Bipolar polygenic loading and bipolar spectrum features in major depressive disorder

NARCIS (Netherlands)

Wiste, Anna; Robinson, Elise B.; Milaneschi, Yuri; Meier, Sandra; Ripke, Stephan; Clements, Caitlin C.; Fitzmaurice, Garrett M.; Rietschel, Marcella; Penninx, Brenda W.; Smoller, Jordan W.; Perlis, Roy H.

Objectives Family and genetic studies indicate overlapping liability for major depressive disorder and bipolar disorder. The purpose of the present study was to determine whether this shared genetic liability influences clinical presentation. Methods A polygenic risk score for bipolar disorder,

Early Intervention in Bipolar Disorder.

Science.gov (United States)

Vieta, Eduard; Salagre, Estela; Grande, Iria; Carvalho, André F; Fernandes, Brisa S; Berk, Michael; Birmaher, Boris; Tohen, Mauricio; Suppes, Trisha

2018-05-01

Bipolar disorder is a recurrent disorder that affects more than 1% of the world population and usually has its onset during youth. Its chronic course is associated with high rates of morbidity and mortality, making bipolar disorder one of the main causes of disability among young and working-age people. The implementation of early intervention strategies may help to change the outcome of the illness and avert potentially irreversible harm to patients with bipolar disorder, as early phases may be more responsive to treatment and may need less aggressive therapies. Early intervention in bipolar disorder is gaining momentum. Current evidence emerging from longitudinal studies indicates that parental early-onset bipolar disorder is the most consistent risk factor for bipolar disorder. Longitudinal studies also indicate that a full-blown manic episode is often preceded by a variety of prodromal symptoms, particularly subsyndromal manic symptoms, therefore supporting the existence of an at-risk state in bipolar disorder that could be targeted through early intervention. There are also identifiable risk factors that influence the course of bipolar disorder, some of them potentially modifiable. Valid biomarkers or diagnosis tools to help clinicians identify individuals at high risk of conversion to bipolar disorder are still lacking, although there are some promising early results. Pending more solid evidence on the best treatment strategy in early phases of bipolar disorder, physicians should carefully weigh the risks and benefits of each intervention. Further studies will provide the evidence needed to finish shaping the concept of early intervention. AJP AT 175 Remembering Our Past As We Envision Our Future April 1925: Interpretations of Manic-Depressive Phases Earl Bond and G.E. Partridge reviewed a number of patients with manic-depressive illness in search of a unifying endo-psychic conflict. They concluded that understanding either phase of illness was "elusive" and

Virginia Woolf, neuroprogression, and bipolar disorder

Directory of Open Access Journals (Sweden)

Manuela V. Boeira

2016-01-01

Full Text Available Family history and traumatic experiences are factors linked to bipolar disorder. It is known that the lifetime risk of bipolar disorder in relatives of a bipolar proband are 5-10% for first degree relatives and 40-70% for monozygotic co-twins. It is also known that patients with early childhood trauma present earlier onset of bipolar disorder, increased number of manic episodes, and more suicide attempts. We have recently reported that childhood trauma partly mediates the effect of family history on bipolar disorder diagnosis. In light of these findings from the scientific literature, we reviewed the work of British writer Virginia Woolf, who allegedly suffered from bipolar disorder. Her disorder was strongly related to her family background. Moreover, Virginia Woolf was sexually molested by her half siblings for nine years. Her bipolar disorder symptoms presented a pernicious course, associated with hospitalizations, suicidal behavioral, and functional impairment. The concept of neuroprogression has been used to explain the clinical deterioration that takes places in a subgroup of bipolar disorder patients. The examination of Virgina Woolf’s biography and art can provide clinicians with important insights about the course of bipolar disorder.

Nonimmune cells equipped with T-cell-receptor-like signaling for cancer cell ablation.

Science.gov (United States)

Kojima, Ryosuke; Scheller, Leo; Fussenegger, Martin

2018-01-01

The ability to engineer custom cell-contact-sensing output devices into human nonimmune cells would be useful for extending the applicability of cell-based cancer therapies and for avoiding risks associated with engineered immune cells. Here we have developed a new class of synthetic T-cell receptor-like signal-transduction device that functions efficiently in human nonimmune cells and triggers release of output molecules specifically upon sensing contact with a target cell. This device employs an interleukin signaling cascade, whose OFF/ON switching is controlled by biophysical segregation of a transmembrane signal-inhibitory protein from the sensor cell-target cell interface. We further show that designer nonimmune cells equipped with this device driving expression of a membrane-penetrator/prodrug-activating enzyme construct could specifically kill target cells in the presence of the prodrug, indicating its potential usefulness for target-cell-specific, cell-based enzyme-prodrug cancer therapy. Our study also contributes to the advancement of synthetic biology by extending available design principles to transmit extracellular information to cells.

CRY2 is associated with rapid cycling in bipolar disorder patients.

Directory of Open Access Journals (Sweden)

Louise K Sjöholm

2010-09-01

Full Text Available Bipolar disorder patients often display abnormalities in circadian rhythm, and they are sensitive to irregular diurnal rhythms. CRY2 participates in the core clock that generates circadian rhythms. CRY2 mRNA expression in blood mononuclear cells was recently shown to display a marked diurnal variation and to respond to total sleep deprivation in healthy human volunteers. It was also shown that bipolar patients in a depressive state had lower CRY2 mRNA levels, nonresponsive to total sleep deprivation, compared to healthy controls, and that CRY2 gene variation was associated with winter depression in both Swedish and Finnish cohorts.Four CRY2 SNPs spanning from intron 2 to downstream 3'UTR were analyzed for association to bipolar disorder type 1 (n = 497, bipolar disorder type 2 (n = 60 and bipolar disorder with the feature rapid cycling (n = 155 versus blood donors (n = 1044 in Sweden. Also, the rapid cycling cases were compared with bipolar disorder cases without rapid cycling (n = 422. The haplotype GGAC was underrepresented among rapid cycling cases versus controls and versus bipolar disorder cases without rapid cycling (OR = 0.7, P = 0.006-0.02, whereas overrepresentation among rapid cycling cases was seen for AAAC (OR = 1.3-1.4, P = 0.03-0.04 and AGGA (OR = 1.5, P = 0.05. The risk and protective CRY2 haplotypes and their effect sizes were similar to those recently suggested to be associated with winter depression in Swedes.We propose that the circadian gene CRY2 is associated with rapid cycling in bipolar disorder. This is the first time a clock gene is implicated in rapid cycling, and one of few findings showing a molecular discrimination between rapid cycling and other forms of bipolar disorder.

Epidemiology in Pediatric Bipolar Disorder

Directory of Open Access Journals (Sweden)

Caner Mutlu

2015-12-01

Full Text Available Childhood and adolescent bipolar disorder diagnosis has been increasing recently. Since studies evaluating attempted suicide rates in children and adolescents have shown bipolarity to be a significant risk factor, diagnosis and treatment of bipolarity has become a very important issue. Since there is a lack of specific diagnostic criteria for especially preadolescent samples and evaluations are made mostly symptomatically, suspicions about false true diagnosis and increased prevalence rates have emerged. This situation leads to controversial data about the prevalence rates of bipolar disorder in children and adolescents. The aim of this article is to review the prevalence of childhood and adolescent bipolar disorder in community, inpatient and outpatient based samples in literature.

BIPOLAR DISORDER: A REVIEW

OpenAIRE

Pathan Dilnawaz N; Ziyaurrahaman A.R; Bhise K.S.

2010-01-01

Bipolar disorder (BD) is a severe psychiatric disorder that results in poor global functioning, reduced quality of life and high relapse rates. Research finds that many adults with bipolar disorder identify the onset of symptoms in childhood and adolescence, indicating the importance of early accurate diagnosis and treatment. Accurate diagnosis of mood disorders is critical for treatment to be effective. Distinguishing between major depression and bipolar disorders, especially the depressed p...

Securing Communication via Transmission of Artificial Noise by Both Sides: Bipolar-Beamforming Optimization

Directory of Open Access Journals (Sweden)

Yongkai Zhou

2013-01-01

Full Text Available The paper considers the secure transmission in a wireless environment in which both the transmitter (Alice and the legitimate receiver (Bob send artificial noise (AN to interfere with the eavesdropper (Eve. Optimal design is analyzed in detail for this AN-by-both-side model to deal with Eve’s stochastic channel condition and random spatial distribution. Bipolar-beamforming is first proposed to jointly design Alice and Bob’s transmitting signals. By optimally assigning the transmitting antenna for Bob and allocating the power ratio between Alice’s information and the AN signal, maximum secrecy capacity can be achieved. Simulation is done to illustrate the process of bipolar-beamforming optimization. Results show that the AN-by-both-side model has good secrecy performance on both average and extreme conditions as Eve approaches Alice or Bob.

Illegitimate WNT signaling promotes proliferation of multiple myeloma cells

Science.gov (United States)

Derksen, Patrick W. B.; Tjin, Esther; Meijer, Helen P.; Klok, Melanie D.; Mac Gillavry, Harold D.; van Oers, Marinus H. J.; Lokhorst, Henk M.; Bloem, Andries C.; Clevers, Hans; Nusse, Roel; van der Neut, Ronald; Spaargaren, Marcel; Pals, Steven T.

2004-01-01

The unrestrained growth of tumor cells is generally attributed to mutations in essential growth control genes, but tumor cells are also influenced by signals from the environment. In multiple myeloma (MM), the factors and signals coming from the bone marrow microenvironment are possibly even essential for the growth of the tumor cells. As targets for intervention, these signals may be equally important as mutated oncogenes. Given their oncogenic potential, WNT signals form a class of paracrine growth factors that could act to influence MM cell growth. In this paper, we report that MM cells have hallmarks of active WNT signaling, whereas the cells have not undergone detectable mutations in WNT signaling genes such as adenomatous polyposis coli and β-catenin (CTNNB1). We show that the malignant MM plasma cells overexpress β-catenin, including its N-terminally unphosphorylated form, suggesting active β-catenin/T cell factor-mediated transcription. Further accumulation and nuclear localization of β-catenin, and/or increased cell proliferation, was achieved by stimulation of WNT signaling with either Wnt3a, LiCl, or the constitutively active S33Y mutant of β-catenin. In contrast, by blocking WNT signaling by dominant-negative T cell factor, we can interfere with the growth of MM cells. We therefore suggest that MM cells are dependent on an active WNT signal, which may have important implications for the management of this incurable form of cancer. PMID:15067127

Differential TCR signals for T helper cell programming.

Science.gov (United States)

Morel, Penelope A

2018-05-02

Upon encounter with their cognate antigen naïve CD4 T cells become activated and are induced to differentiate into several possible T helper (Th) cell subsets. This differentiation depends on a number of factors including antigen presenting cells, cytokines and costimulatory molecules. The strength of the T cell receptor (TCR) signal, related to the affinity of TCR for antigen and antigen dose, has emerged as a dominant factor in determining Th cell fate. Recent studies have revealed that TCR signals of high or low strength do not simply induce quantitatively different signals in the T cells, but rather qualitatively distinct pathways can be induced based on TCR signal strength. This review examines the recent literature in this area and highlights important new developments in our understanding of Th cell differentiation and TCR signal strength. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Test results of a 60 volt bipolar nickel-hydrogen battery

Science.gov (United States)

Cataldo, Robert L.; Gonzalez-Sanabria, Olga; Gahn, Randall F.; Manzo, Michelle A.; Gemeiner, Russel P.

1987-01-01

In July 1986, a high-voltage nickel-hydrogen battery was assembled at the NASA Lewis Research Center. This battery incorporated bipolar construction techniques to build a 50-cell stack with approximately 1.0 A-hr capacity (C) and an open-circuit voltage of 65 V. The battery was characterized at both low and high current rates prior to pulsed and nonpulsed discharges. Pulse discharges at 5 and 10 C were performed before placing the battery on over 1400, 40-percent depth-of-discharge, low-earth-orbit cycles. The successful demonstration of a high-voltage bipolar battery in one containment vessel has advanced the technology to where nickel-hydrogen high-voltage systems can be constructed of several modules instead of hundreds of individual cells.

CT-guided Bipolar and Multipolar Radiofrequency Ablation (RF Ablation) of Renal Cell Carcinoma: Specific Technical Aspects and Clinical Results

International Nuclear Information System (INIS)

Sommer, C. M.; Lemm, G.; Hohenstein, E.; Bellemann, N.; Stampfl, U.; Goezen, A. S.; Rassweiler, J.; Kauczor, H. U.; Radeleff, B. A.; Pereira, P. L.

2013-01-01

Purpose. This study was designed to evaluate the clinical efficacy of CT-guided bipolar and multipolar radiofrequency ablation (RF ablation) of renal cell carcinoma (RCC) and to analyze specific technical aspects between both technologies. Methods. We included 22 consecutive patients (3 women; age 74.2 ± 8.6 years) after 28 CT-guided bipolar or multipolar RF ablations of 28 RCCs (diameter 2.5 ± 0.8 cm). Procedures were performed with a commercially available RF system (Celon AG Olympus, Berlin, Germany). Technical aspects of RF ablation procedures (ablation mode [bipolar or multipolar], number of applicators and ablation cycles, overall ablation time and deployed energy, and technical success rate) were analyzed. Clinical results (local recurrence-free survival and local tumor control rate, renal function [glomerular filtration rate (GFR)]) and complication rates were evaluated. Results. Bipolar RF ablation was performed in 12 procedures and multipolar RF ablation in 16 procedures (2 applicators in 14 procedures and 3 applicators in 2 procedures). One ablation cycle was performed in 15 procedures and two ablation cycles in 13 procedures. Overall ablation time and deployed energy were 35.0 ± 13.6 min and 43.7 ± 17.9 kJ. Technical success rate was 100 %. Major and minor complication rates were 4 and 14 %. At an imaging follow-up of 15.2 ± 8.8 months, local recurrence-free survival was 14.4 ± 8.8 months and local tumor control rate was 93 %. GFR did not deteriorate after RF ablation (50.8 ± 16.6 ml/min/1.73 m 2 before RF ablation vs. 47.2 ± 11.9 ml/min/1.73 m 2 after RF ablation; not significant). Conclusions. CT-guided bipolar and multipolar RF ablation of RCC has a high rate of clinical success and low complication rates. At short-term follow-up, clinical efficacy is high without deterioration of the renal function.

Experimental demonstration of all-optical CDMA using bipolar codes

Science.gov (United States)

Dennis, Tasshi

1999-10-01

Fiber optic networks capable of supporting a large pool of subscribers, many simultaneous users, and high data rates are receiving heightened interest as solutions to a growing communications need. The experiments reported in this study constitute the first experimental demonstration of a novel bipolar equivalent code-division multiple-access (CDMA) scheme. The sophisticated encoding increases noise tolerance, provides user security, and enables network flexibility. The scheme is based on an established bipolar radio frequency (RF) technique adapted to the unipolar optical domain. Whereas the phase of an RF signal can be readily detected, the high carrier frequency ( ~ 200 THz at 1.5 μm) of an optical wave necessitates that optical signals be detected and processed solely by intensity. Asynchronous operation makes the CDMA scheme data rate independent, while all-optical implementation avoids the bandwidth limitations imposed by electrical processing. A proof-of-principle experiment was conducted by spectrally encoding an erbium-doped superfluorescent fiber source (SFS) using a diffraction grating and an amplitude mask. The optical properties of the system were measured and the bipolar correlation of codes was verified. The practical implementation of the scheme was investigated by the design, construction, and operation of a fiber-based testbed. Correlation measurements performed with modulated signals confirmed that the scheme can recover a binary information symbol while rejecting multiple access interference. A theoretical analysis of the optical correlation process was conducted, which identified key optical parameters important to future implementations. The theory of excess noise associated with the photodetection of a thermal source was considered, followed by noise measurements of a light bulb and the erbium-doped SFS used for spectral encoding. Finally, the ability of the proposed scheme to effectively transmit data was investigated. Signal-to- noise

Thyroid Hormone Signaling in the Mouse Retina.

Directory of Open Access Journals (Sweden)

Patrick Arbogast

Full Text Available Thyroid hormone is a crucial regulator of gene expression in the developing and adult retina. Here we sought to map sites of thyroid hormone signaling at the cellular level using the transgenic FINDT3 reporter mouse model in which neurons express β-galactosidase (β-gal under the control of a hybrid Gal4-TRα receptor when triiodothyronine (T3 and cofactors of thyroid receptor signaling are present. In the adult retina, nearly all neurons of the ganglion cell layer (GCL, ganglion cells and displaced amacrine cells showed strong β-gal labeling. In the inner nuclear layer (INL, a minority of glycineric and GABAergic amacrine cells showed β-gal labeling, whereas the majority of amacrine cells were unlabeled. At the level of amacrine types, β-gal labeling was found in a large proportion of the glycinergic AII amacrines, but only in a small proportion of the cholinergic/GABAergic 'starburst' amacrines. At postnatal day 10, there also was a high density of strongly β-gal-labeled neurons in the GCL, but only few amacrine cells were labeled in the INL. There was no labeling of bipolar cells, horizontal cells and Müller glia cells at both stages. Most surprisingly, the photoreceptor somata in the outer nuclear layer also showed no β-gal label, although thyroid hormone is known to control cone opsin expression. This is the first record of thyroid hormone signaling in the inner retina of an adult mammal. We hypothesize that T3 levels in photoreceptors are below the detection threshold of the reporter system. The topographical distribution of β-gal-positive cells in the GCL follows the overall neuron distribution in that layer, with more T3-signaling cells in the ventral than the dorsal half-retina.

Application of bipolar electrodialysis to E.coli fermentation for simultaneous acetate removal and pH control

DEFF Research Database (Denmark)

Wong, M.; Woodley, John; Lye, G.J.

2010-01-01

The application of bipolar electrodialysis (BPED) for the simultaneous removal of inhibitory acetate and pH control during E. coli fermentation was investigated. A two cell pair electrodialysis module, consisting of cation exchange, anion exchange and bipolar membranes with working area of 100 cm2...

Recent Advances in the Study of Bipolar/Rod-Shaped Microglia and their Roles in Neurodegeneration

Directory of Open Access Journals (Sweden)

Ngan Pan Bennett Au

2017-05-01

Full Text Available Microglia are the resident immune cells of the central nervous system (CNS and they contribute to primary inflammatory responses following CNS injuries. The morphology of microglia is closely associated with their functional activities. Most previous research efforts have attempted to delineate the role of ramified and amoeboid microglia in the pathogenesis of neurodegenerative diseases. In addition to ramified and amoeboid microglia, bipolar/rod-shaped microglia were first described by Franz Nissl in 1899 and their presence in the brain was closely associated with the pathology of infectious diseases and sleeping disorders. However, studies relating to bipolar/rod-shaped microglia are very limited, largely due to the lack of appropriate in vitro and in vivo experimental models. Recent studies have reported the formation of bipolar/rod-shaped microglia trains in in vivo models of CNS injury, including diffuse brain injury, focal transient ischemia, optic nerve transection and laser-induced ocular hypertension (OHT. These bipolar/rod-shaped microglia formed end-to-end alignments in close proximity to the adjacent injured axons, but they showed no interactions with blood vessels or other types of glial cell. Recent studies have also reported on a highly reproducible in vitro culture model system to enrich bipolar/rod-shaped microglia that acts as a powerful tool with which to characterize this form of microglia. The molecular aspects of bipolar/rod-shaped microglia are of great interest in the field of CNS repair. This review article focuses on studies relating to the morphology and transformation of microglia into the bipolar/rod-shaped form, along with the differential gene expression and spatial distribution of bipolar/rod-shaped microglia in normal and pathological CNSs. The spatial arrangement of bipolar/rod-shaped microglia is crucial in the reorganization and remodeling of neuronal and synaptic circuitry following CNS injuries. Finally, we

Bipolar nickel-hydrogen battery development

Science.gov (United States)

Koehler, C. W.; Applewhite, A. Z.; Hall, A. M.; Russell, P. G.

1985-01-01

A comparison of the bipolar Ni-H2 battery with other energy systems to be used in future high-power space systems is presented. The initial design for the battery under the NASA-sponsored program is described and the candidate stack components are evaluated, including electrodes, separator, electrolyte reservoir plate, and recombination sites. The compressibility of the cell elements, electrolyte activation, and thermal design are discussed. Manufacturing and prototype test results are summarized.

The retina of the shovel-nosed ray, Rhinobatos batillum (Rhinobatidae): morphology and quantitative analysis of the ganglion, amacrine and bipolar cell populations.

Science.gov (United States)

Collin, S P

1988-01-01

A light microscopy study of the retina of the shovel-nosed ray, Rhinobatos batillum (Rhinobatidae) has revealed a duplex retina with a rod to cone ratio between 4:1 and 6:1. The inner nuclear layer consists of three layers of large horizontal cells, tightly packed, stellate bipolar cells, and up to three substrata of amacrine cells. The collaterals of the many supporting Müller cells project from the inner to the outer limiting membrane and divide the retina into many subunits. The cells of the ganglion cell layer are distributed into two layers, although a large proportion of ganglion cells are also displaced into the inner plexiform and inner nuclear layers. Topographic analysis of the cells in the ganglion cell layer, inner plexiform and inner nuclear layers reveals a number of regional specializations or "areae centrales". Ganglion cells were retrogradely-labelled with cobalt-lysine from the optic nerve, and three sub-populations of neurons characterized on their soma size and position. Small (20-50 microns2), large (80-300 microns2) and giant (greater than 300 microns2) sub-populations of ganglion cells each revealed distinct retinal specializations with peak densities of 3 x 10(3), 1.25 x 10(3) and 1.57 x 10(3) cells per mm2, respectively. Topographical comparison between Nissl-stained and retrogradely-labelled ganglion cell populations have established that a maximum of 20% in the "area centralis", and 75% in unspecialized, peripheral regions of the retina are non-ganglion cells. Out of a total of 210,566 cells in the ganglion cell layer, 49% were found to be non-ganglion cells. Iso-density contour maps of amacrine and bipolar cell distributions also reveal some specializations. These cell concentrations lie in corresponding regions to areas of increased density in the large and giant ganglion cell populations, suggesting some functional association.

Parametric and cycle tests of a 40-A-hr bipolar nickel-hydrogen battery

Science.gov (United States)

Cataldo, R. L.

1986-01-01

A series of tests was performed to characterize battery performance relating to certain operating parameters which included charge current, discharge current, temperature and pressure. The parameters were varied to confirm battery design concepts and to determine optimal operating conditions. Spacecraft power requirements are constantly increasing. Special spacecraft such as the Space Station and platforms will require energy storage systems of 130 and 25 kWh, respectively. The complexity of these high power systems will demand high reliability, and reduced mass and volume. A system that uses batteries for storage will require a cell count in excess of 400 units. These cell units must then be assembled into several batteries with over 100 cells in a series connected string. In an attempt to simplify the construction of conventional cells and batteries, the NASA Lewis Research Center battery systems group initiated work on a nickel-hydrogen battery in a bipolar configuration in early 1981. Features of the battery with this bipolar construction show promise in improving both volumetric and gravimetric energy densities as well as thermal management. Bipolar construction allows cooling in closer proximity to the cell components, thus heat removal can be accomplished at a higher rejection temperature than conventional cell designs. Also, higher current densities are achievable because of low cell impedance. Lower cell impedance is achieved via current flow perpendicular to the electrode face, thus reducing voltage drops in the electrode grid and electrode terminals tabs.

A bipolar analog front-end integrated circuit for the SDC silicon tracker

International Nuclear Information System (INIS)

Kipnis, I.; Spieler, H.; Collins, T.

1993-11-01

A low-noise, low-power, high-bandwidth, radiation hard, silicon bipolar-transistor full-custom integrated circuit (IC) containing 64 channels of analog signal processing has been developed for the SDC silicon tracker. The IC was designed and tested at LBL and was fabricated using AT ampersand T's CBIC-U2, 4 GHz f T complementary bipolar technology. Each channel contains the following functions: low-noise preamplification, pulse shaping and threshold discrimination. This is the first iteration of the production analog IC for the SDC silicon tracker. The IC is laid out to directly match the 50 μm pitch double-sided silicon strip detector. The chip measures 6.8 mm x 3.1 mm and contains 3,600 transistors. Three stages of amplification provide 180 mV/fC of gain with a 35 nsec peaking time at the comparator input. For a 14 pF detector capacitance, the equivalent noise charge is 1300 el. rms at a power consumption of 1 mW/channel from a single 3.5 V supply. With the discriminator threshold set to 4 times the noise level, a 16 nsec time-walk for 1.25 to 10fC signals is achieved using a time-walk compensation network. Irradiation tests at TRIUMF to a Φ=10 14 protons/cm 2 have been performed on the IC, demonstrating the radiation hardness of the complementary bipolar process

Six years of evidence-based adult dissection tonsillectomy with ultrasonic scalpel, bipolar electrocautery, bipolar radiofrequency or 'cold steel' dissection.

Science.gov (United States)

Ragab, S M

2012-10-01

To conduct an adequately powered, prospective, randomised, controlled trial comparing adult dissection tonsillectomy using either ultrasonic scalpel, bipolar electrocautery, bipolar radiofrequency or 'cold steel' dissection. Three hundred patients were randomised into four tonsillectomy technique groups. The operative time, intra-operative bleeding, post-operative pain, tonsillar fossa healing, return to full diet, return to work and post-operative complications were recorded. The bipolar radiofrequency group had a shorter mean operative time. The mean intra-operative blood loss during bipolar radiofrequency tonsillectomy was significantly less compared with cold dissection and ultrasonic scalpel tonsillectomy. Pain scores were significantly higher after bipolar electrocautery tonsillectomy. Patients undergoing bipolar electrocautery tonsillectomy required significantly more days to return to full diet and work. The bipolar electrocautery group showed significantly reduced tonsillar fossa healing during the first and second post-operative weeks. In this adult series, bipolar radiofrequency tonsillectomy was superior to ultrasonic, bipolar electrocautery and cold dissection tonsillectomies. This method combines the advantages of 'hot' and 'cold' tonsillectomy.

Course of Subthreshold Bipolar Disorder in Youth: Diagnostic Progression from Bipolar Disorder Not Otherwise Specified

Science.gov (United States)

Axelson, David A.; Birmaher, Boris; Strober, Michael A.; Goldstein, Benjamin I.; Ha, Wonho; Gill, Mary Kay; Goldstein, Tina R.; Yen, Shirley; Hower, Heather; Hunt, Jeffrey I.; Liao, Fangzi; Iyengar, Satish; Dickstein, Daniel; Kim, Eunice; Ryan, Neal D.; Frankel, Erica; Keller, Martin B.

2011-01-01

Objective: To determine the rate of diagnostic conversion from an operationalized diagnosis of bipolar disorder not otherwise specified (BP-NOS) to bipolar I disorder (BP-I) or bipolar II disorder (BP-II) in youth over prospective follow-up and to identify factors associated with conversion. Method: Subjects were 140 children and adolescents…

Mechanisms underlying the benefits of anticonvulsants over lithium in the treatment of bipolar disorder.

Science.gov (United States)

Corrado, Alisa C; Walsh, John P

2016-02-10

Close to 3% of the world's population suffers from bipolar disease (I and II). Of this 3%, bipolar disease affects largely women (∼ 3 : 2 compared with men). The median age of diagnosis is 25 in women and even lower in men. A diagnosis of bipolar disease is an expensive psychiatric diagnosis, costing patients more than twice as much money as a diagnosis of unipolar depression. Bipolar I is characterized by one or more manic or mixed episodes, with both mania and depression occurring each day for at least 1 week, whereas bipolar II is characterized by one or more major depressive episode and at least one episode of hypomania. Bipolar I is the more severe diagnosis. A wide range of medications are available to help patients maintain a healthy lifestyle, including lithium, antidepressants, and anticonvulsants. Improved methods for identifying bipolar disease, including a more structured approach and a more complete use of medical records, have increased the rate of diagnosis, especially in children, which underscores the need for innovation in development and in practice of new treatment options for treating bipolar disease. Although lithium has been the 'gold standard' for treating bipolar disorder for decades, new research into other forms of treatment has shown anticonvulsants to be a particularly useful therapy for treating bipolar disease. Anticonvulsants have remarkable mood-stabilization abilities and they do not lead to serious side effects, which increases the tolerability, and consequently, patient adherence to this form of treatment. Recent studies have shown that anticonvulsants improve behavior in bipolar disease by modulating the balance of excitatory and inhibitory synapses through a number of complementary molecular cascades that affect gene expression and cell survival.

The International Society for Bipolar Disorders (ISBD) Task Force Report on Antidepressant Use in Bipolar Disorders

Science.gov (United States)

Pacchiarotti, Isabella; Bond, David J.; Baldessarini, Ross J.; Nolen, Willem A.; Grunze, Heinz; Licht, Rasmus W.; Post, Robert M.; Berk, Michael; Goodwin, Guy M.; Sachs, Gary S.; Tondo, Leonardo; Findling, Robert L.; Youngstrom, Eric A.; Tohen, Mauricio; Undurraga, Juan; González-Pinto, Ana; Goldberg, Joseph F.; Yildiz, Ayşegül; Altshuler, Lori L.; Calabrese, Joseph R.; Mitchell, Philip B.; Thase, Michael E.; Koukopoulos, Athanasios; Colom, Francesc; Frye, Mark A.; Malhi, Gin S.; Fountoulakis, Konstantinos N.; Vázquez, Gustavo; Perlis, Roy H.; Ketter, Terence A.; Cassidy, Frederick; Akiskal, Hagop; Azorin, Jean-Michel; Valentí, Marc; Mazzei, Diego Hidalgo; Lafer, Beny; Kato, Tadafumi; Mazzarini, Lorenzo; Martínez-Aran, Anabel; Parker, Gordon; Souery, Daniel; Özerdem, Ayşegül; McElroy, Susan L.; Girardi, Paolo; Bauer, Michael; Yatham, Lakshmi N.; Zarate, Carlos A.; Nierenberg, Andrew A.; Birmaher, Boris; Kanba, Shigenobu; El-Mallakh, Rif S.; Serretti, Alessandro; Rihmer, Zoltan; Young, Allan H.; Kotzalidis, Georgios D.; MacQueen, Glenda M.; Bowden, Charles L.; Ghaemi, S. Nassir; Lopez-Jaramillo, Carlos; Rybakowski, Janusz; Ha, Kyooseob; Perugi, Giulio; Kasper, Siegfried; Amsterdam, Jay D.; Hirschfeld, Robert M.; Kapczinski, Flávio; Vieta, Eduard

2014-01-01

Objective The risk-benefit profile of antidepressant medications in bipolar disorder is controversial. When conclusive evidence is lacking, expert consensus can guide treatment decisions. The International Society for Bipolar Disorders (ISBD) convened a task force to seek consensus recommendations on the use of antidepressants in bipolar disorders. Method An expert task force iteratively developed consensus through serial consensus-based revisions using the Delphi method. Initial survey items were based on systematic review of the literature. Subsequent surveys included new or reworded items and items that needed to be rerated. This process resulted in the final ISBD Task Force clinical recommendations on antidepressant use in bipolar disorder. Results There is striking incongruity between the wide use of and the weak evidence base for the efficacy and safety of antidepressant drugs in bipolar disorder. Few well-designed, long-term trials of prophylactic benefits have been conducted, and there is insufficient evidence for treatment benefits with antidepressants combined with mood stabilizers. A major concern is the risk for mood switch to hypomania, mania, and mixed states. Integrating the evidence and the experience of the task force members, a consensus was reached on 12 statements on the use of antidepressants in bipolar disorder. Conclusions Because of limited data, the task force could not make broad statements endorsing antidepressant use but acknowledged that individual bipolar patients may benefit from antidepressants. Regarding safety, serotonin reuptake inhibitors and bupropion may have lower rates of manic switch than tricyclic and tetracyclic antidepressants and norepinephrine-serotonin reuptake inhibitors. The frequency and severity of antidepressant-associated mood elevations appear to be greater in bipolar I than bipolar II disorder. Hence, in bipolar I patients antidepressants should be prescribed only as an adjunct to mood-stabilizing medications

Inhibitory neurons modulate spontaneous signaling in cultured cortical neurons: density-dependent regulation of excitatory neuronal signaling

International Nuclear Information System (INIS)

Serra, Michael; Guaraldi, Mary; Shea, Thomas B

2010-01-01

Cortical neuronal activity depends on a balance between excitatory and inhibitory influences. Culturing of neurons on multi-electrode arrays (MEAs) has provided insight into the development and maintenance of neuronal networks. Herein, we seeded MEAs with murine embryonic cortical/hippocampal neurons at different densities ( 1000 cells mm −2 ) and monitored resultant spontaneous signaling. Sparsely seeded cultures displayed a large number of bipolar, rapid, high-amplitude individual signals with no apparent temporal regularity. By contrast, densely seeded cultures instead displayed clusters of signals at regular intervals. These patterns were observed even within thinner and thicker areas of the same culture. GABAergic neurons (25% of total neurons in our cultures) mediated the differential signal patterns observed above, since addition of the inhibitory antagonist bicuculline to dense cultures and hippocampal slice cultures induced the signal pattern characteristic of sparse cultures. Sparsely seeded cultures likely lacked sufficient inhibitory neurons to modulate excitatory activity. Differential seeding of MEAs can provide a unique model for analyses of pertubation in the interaction between excitatory and inhibitory function during aging and neuropathological conditions where dysregulation of GABAergic neurons is a significant component

Signaling hierarchy regulating human endothelial cell development.

Science.gov (United States)

Kelly, Melissa A; Hirschi, Karen K

2009-05-01

Our present knowledge of the regulation of mammalian endothelial cell differentiation has been largely derived from studies of mouse embryonic development. However, unique mechanisms and hierarchy of signals that govern human endothelial cell development are unknown and, thus, explored in these studies. Using human embryonic stem cells as a model system, we were able to reproducibly and robustly generate differentiated endothelial cells via coculture on OP9 marrow stromal cells. We found that, in contrast to studies in the mouse, bFGF and VEGF had no specific effects on the initiation of human vasculogenesis. However, exogenous Ihh promoted endothelial cell differentiation, as evidenced by increased production of cells with cobblestone morphology that coexpress multiple endothelial-specific genes and proteins, form lumens, and exhibit DiI-AcLDL uptake. Inhibition of BMP signaling using Noggin or BMP4, specifically, using neutralizing antibodies suppressed endothelial cell formation; whereas, addition of rhBMP4 to cells treated with the hedgehog inhibitor cyclopamine rescued endothelial cell development. Our studies revealed that Ihh promoted human endothelial cell differentiation from pluripotent hES cells via BMP signaling, providing novel insights applicable to modulating human endothelial cell formation and vascular regeneration for human clinical therapies.

Guard Cell Signal Transduction Network: Advances in Understanding Abscisic Acid, CO2, and Ca2+ Signaling

KAUST Repository

Kim, Tae-Houn

2010-05-04

Stomatal pores are formed by pairs of specialized epidermal guard cells and serve as major gateways for both CO2 influx into plants from the atmosphere and transpirational water loss of plants. Because they regulate stomatal pore apertures via integration of both endogenous hormonal stimuli and environmental signals, guard cells have been highly developed as a model system to dissect the dynamics and mechanisms of plant-cell signaling. The stress hormone ABA and elevated levels of CO2 activate complex signaling pathways in guard cells that are mediated by kinases/phosphatases, secondary messengers, and ion channel regulation. Recent research in guard cells has led to a new hypothesis for how plants achieve specificity in intracellular calcium signaling: CO2 and ABA enhance (prime) the calcium sensitivity of downstream calcium-signaling mechanisms. Recent progress in identification of early stomatal signaling components are reviewed here, including ABA receptors and CO2-binding response proteins, as well as systems approaches that advance our understanding of guard cell-signaling mechanisms.

Guard Cell Signal Transduction Network: Advances in Understanding Abscisic Acid, CO2, and Ca2+ Signaling

KAUST Repository

Kim, Tae-Houn; Bö hmer, Maik; Hu, Honghong; Nishimura, Noriyuki; Schroeder, Julian I.

2010-01-01

Stomatal pores are formed by pairs of specialized epidermal guard cells and serve as major gateways for both CO2 influx into plants from the atmosphere and transpirational water loss of plants. Because they regulate stomatal pore apertures via integration of both endogenous hormonal stimuli and environmental signals, guard cells have been highly developed as a model system to dissect the dynamics and mechanisms of plant-cell signaling. The stress hormone ABA and elevated levels of CO2 activate complex signaling pathways in guard cells that are mediated by kinases/phosphatases, secondary messengers, and ion channel regulation. Recent research in guard cells has led to a new hypothesis for how plants achieve specificity in intracellular calcium signaling: CO2 and ABA enhance (prime) the calcium sensitivity of downstream calcium-signaling mechanisms. Recent progress in identification of early stomatal signaling components are reviewed here, including ABA receptors and CO2-binding response proteins, as well as systems approaches that advance our understanding of guard cell-signaling mechanisms.

Iron-based alloy and nitridation treatment for PEM fuel cell bipolar plates

Science.gov (United States)

Brady, Michael P [Oak Ridge, TN; Yang, Bing [Oak Ridge, TN; Maziasz, Philip J [Oak Ridge, TN

2010-11-09

A corrosion resistant electrically conductive component that can be used as a bipolar plate in a PEM fuel cell application is composed of an alloy substrate which has 10-30 wt. % Cr, 0.5 to 7 wt. % V, and base metal being Fe, and a continuous surface layer of chromium nitride and vanadium nitride essentially free of base metal. A oxide layer of chromium vanadium oxide can be disposed between the alloy substrate and the continuous surface nitride layer. A method to prepare the corrosion resistant electrically conductive component involves a two-step nitridization sequence by exposing the alloy to a oxygen containing gas at an elevated temperature, and subsequently exposing the alloy to an oxygen free nitrogen containing gas at an elevated temperature to yield a component where a continuous chromium nitride layer free of iron has formed at the surface.

Bipolar disorder and age-related functional impairment Prejuízo funcional associado à idade e transtorno bipolar

Directory of Open Access Journals (Sweden)

Alice Aita Cacilhas

2009-12-01

Full Text Available OBJECTIVE: Although bipolar disorder is a major contributor to functional impairment worldwide, an independent impact of bipolar disorder and ageing on functioning has yet to be demonstrated. The objective of the present study was to evaluate the effect of bipolar disorder on age-related functional status using matched controls as a standard. METHOD: One-hundred patients with bipolar disorder and matched controls were evaluated for disability. Age-related effects controlled for confounders were cross-sectionally evaluated. RESULTS: Patients were significantly more impaired than controls. Regression showed effects for aging in both groups. The effect, size, however, was significantly stronger in patients. CONCLUSION: Bipolar disorder was an important effect modifier of the age impact on functioning. While a longitudinal design is needed to effectively demonstrate this different impact, this study further depicts bipolar disorder as a chronic and progressively impairing illness.OBJETIVO: O transtorno bipolar é responsável por importante parcela do prejuízo funcional ao redor do mundo. Um efeito independente do transtorno bipolar e da idade no funcionamento ainda não foi demonstrado. O presente estudo tem o objetivo de avaliar o efeito do transtorno bipolar no prejuízo funcional relacionado à idade, com controles pareados como padrão. MÉTODO: Cem pacientes com transtorno bipolar e controles pareados foram avaliados para incapacidade. Efeitos relacionados à idade, com controle para confundidores, foram investigados. RESULTADOS: Pacientes tiveram significativamente mais prejuízo que controles. A regressão mostrou efeito para a idade em ambos os grupos, e o efeito foi significativamente mais forte nos pacientes. CONCLUSÃO: O transtorno bipolar foi um importante modificador de efeito no impacto da idade no funcionamento. Enquanto um desenho de estudo longitudinal é necessário para efetivamente demonstrar este impacto diferencial, este

Cognitive vulnerability to bipolar disorder in offspring of parents with bipolar disorder.

Science.gov (United States)

Pavlickova, Hana; Turnbull, Oliver; Bentall, Richard P

2014-11-01

Bipolar disorder is a highly heritable illness, with a positive family history robustly predictive of its onset. It follows that studying biological children of parents with bipolar disorder may provide information about developmental pathways to the disorder. Moreover, such studies may serve as a useful test of theories that attribute a causal role in the development of mood disorders to psychological processes. Psychological style (including self-esteem, coping style with depression, domain-specific risk-taking, sensation-seeking, sensitivity to reward and punishment, and hypomanic personality and cognition) was assessed in 30 offspring of bipolar parents and 30 children of well parents. Parents of both child groups completed identical assessments. Although expected differences between parents with bipolar disorder and well parents were detected (such as low self-esteem, increased rumination, high sensitivity to reward and punishment), offspring of bipolar parents were, as a group, not significantly different from well offspring, apart from a modest trend towards lower adaptive coping. When divided into affected and non-affected subgroups, both groups of index children showed lower novelty-seeking. Only affected index children showed lower self-esteem, increased rumination, sensitivity to punishment, and hypomanic cognitions. Notably, these processes were associated with symptoms of depression. Psychological abnormalities in index offspring were associated with having met diagnostic criteria for psychiatric illnesses and the presence of mood symptoms, rather than preceding them. Implications of the present findings for our understanding of the development of bipolar disorder, as well as for informing early interventions, are discussed. © 2014 The British Psychological Society.

[Lithium and anticonvulsants in bipolar depression].

Science.gov (United States)

Samalin, L; Nourry, A; Llorca, P-M

2011-12-01

For decades, lithium and anticonvulsants have been widely used in the treatment of bipolar disorder. Their efficacy in the treatment of mania is recognized. These drugs have been initially evaluated in old and methodologically heterogeneous studies. Their efficacy in bipolar depression has not always been confirmed in more recent and methodologically more reliable studies. Thus, lithium's efficacy as monotherapy was challenged by the study of Young (2008) that showed a lack of efficacy compared with placebo in the treatment of bipolar depression. In two recent meta-analyses, valproate has shown a modest efficacy in the treatment of bipolar depression. As for lithium, valproate appeared to have a larger antimanic effect for acute phase and prophylaxis of bipolar disorder. In contrast, lamotrigine is more effective on the depressive pole of bipolar disorder with better evidence for the prevention of depressive recurrences. The guidelines include these recent studies and recommend lamotrigine as a first-line treatment of bipolar depression and for maintenance treatment. Because of more discordant data concerning lithium and valproate, these two drugs are placed either as first or as second line treatment of bipolar depression. The different safety/efficacy ratios of mood stabilizers underlie the complementarity and the importance of combination between them, or with some second-generation antipsychotics, in the treatment of patients with bipolar disorder. Copyright © 2011 L’Encéphale. Published by Elsevier Masson SAS.. All rights reserved.

Electropermeabilization by uni- or bipolar nanosecond electric pulses: The impact of extracellular conductivity.

Science.gov (United States)

Gianulis, Elena C; Casciola, Maura; Xiao, Shu; Pakhomova, Olga N; Pakhomov, Andrei G

2018-02-01

Cellular effects caused by nanosecond electric pulses (nsEP) can be reduced by an electric field reversal, a phenomenon known as bipolar cancellation. The reason for this cancellation effect remains unknown. We hypothesized that assisted membrane discharge is the mechanism for bipolar cancellation. CHO-K1 cells bathed in high (16.1mS/cm; HCS) or low (1.8mS/cm; LCS) conductivity solutions were exposed to either one unipolar (300-ns) or two opposite polarity (300+300-ns; bipolar) nsEP (4-40kV/cm) with increasing interpulse intervals (0.1-50μs). Time-lapse YO-PRO-1 (YP) uptake revealed enhanced membrane permeabilization in LCS compared to HCS at all tested voltages. The time-dependence of bipolar cancellation was similar in both solutions, using either identical (22kV/cm) or isoeffective nsEP treatments (12 and 32kV/cm for LCS and HCS, respectively). However, cancellation was significantly stronger in LCS when the bipolar nsEP had no, or very short (bipolar cancellation was still present with interpulse intervals as long as 50μs, beyond the time expected for membrane discharge. Our findings do not support assisted membrane discharge as the mechanism for bipolar cancellation. Instead they exemplify the sustained action of nsEP that can be reversed long after the initial stimulus. Copyright © 2017 Elsevier B.V. All rights reserved.

The role of macrophage polarization on bipolar disorder: Identifying new therapeutic targets.

Science.gov (United States)

Ascoli, Bruna M; Géa, Luiza P; Colombo, Rafael; Barbé-Tuana, Florência M; Kapczinski, Flávio; Rosa, Adriane Ribeiro

2016-07-01

Bipolar disorder is a chronic, severe and disabling disease; however, its pathophysiology remains poorly understood. Recent evidence has suggested that inflammation and immune dysregulation play a significant role in the pathophysiology of bipolar disorder. This review is aimed to highlight the importance of systemic inflammation in modulating the inflammatory response of microglia and hence its potential involvement with bipolar disorder. We also discuss novel therapeutic strategies that emerge from this new research. This article presents a theoretical synthesis of the effects of systemic inflammation on the immune response of the central nervous system in bipolar disorder. The complex relationship between stress, pro-inflammatory cytokines and microglial dysfunction is summarized, emphasizing the role of the kynurenine pathway in this process and, consequently, their effects on neuronal plasticity. Bipolar patients demonstrate increased serum levels of pro-inflammatory cytokines (interleukin-1β, interleukin-6 and tumor necrosis factor-α) and lower hypothalamic-pituitary-adrenal axis sensitivity. This imbalance in the immune system promotes a change in blood-brain barrier permeability, leading to an inflammatory signal spread in the central nervous system from the periphery, through macrophages activation (M1 polarization). Chronic microglial activation can result in neuronal apoptosis, neurogenesis inhibition, hippocampal volume reduction, lower neurotransmitters synthesis and cytotoxicity, by increasing glutamate production and kynurenine metabolism. This review provides an overview of the mechanisms involved in the immune system imbalance and its potential involvement in the pathophysiology of bipolar disorder. Consequently, new strategies that normalize the immune-inflammatory pathways may provide a valuable therapeutic target for the treatment of these disorders. © The Royal Australian and New Zealand College of Psychiatrists 2016.

Application of Bipolar Fuzzy Sets in Graph Structures

Directory of Open Access Journals (Sweden)

Muhammad Akram

2016-01-01

Full Text Available A graph structure is a useful tool in solving the combinatorial problems in different areas of computer science and computational intelligence systems. In this paper, we apply the concept of bipolar fuzzy sets to graph structures. We introduce certain notions, including bipolar fuzzy graph structure (BFGS, strong bipolar fuzzy graph structure, bipolar fuzzy Ni-cycle, bipolar fuzzy Ni-tree, bipolar fuzzy Ni-cut vertex, and bipolar fuzzy Ni-bridge, and illustrate these notions by several examples. We study ϕ-complement, self-complement, strong self-complement, and totally strong self-complement in bipolar fuzzy graph structures, and we investigate some of their interesting properties.

Multikilowatt Bipolar Nickel/Hydrogen Battery

Science.gov (United States)

1986-01-01

High energy densities appear feasible. Nickel/hydrogen battery utilizing bipolar construction in common pressure vessel, addressing needs for multikilowatt storage for low-Earth-orbit applications, designed and 10-cell prototype model tested. Modular-concept-design 35-kW battery projected energy densities of 20 to 24 Wh/b (160 to 190 kj/kg) and 700 to 900 Wh/ft3 (90 to 110 MJ/m3) and incorporated significant improvements over state-of-the-art storage systems.

Chansporter complexes in cell signaling.

Science.gov (United States)

Abbott, Geoffrey W

2017-09-01

Ion channels facilitate diffusion of ions across cell membranes for such diverse purposes as neuronal signaling, muscular contraction, and fluid homeostasis. Solute transporters often utilize ionic gradients to move aqueous solutes up their concentration gradient, also fulfilling a wide variety of tasks. Recently, an increasing number of ion channel-transporter ('chansporter') complexes have been discovered. Chansporter complex formation may overcome what could otherwise be considerable spatial barriers to rapid signal integration and feedback between channels and transporters, the ions and other substrates they transport, and environmental factors to which they must respond. Here, current knowledge in this field is summarized, covering both heterologous expression structure/function findings and potential mechanisms by which chansporter complexes fulfill contrasting roles in cell signaling in vivo. © 2017 Federation of European Biochemical Societies.

A composite peripheral blood gene expression measure as a potential diagnostic biomarker in bipolar disorder

DEFF Research Database (Denmark)

Munkholm, Klaus; Peijs, L; Vinberg, M

2015-01-01

as a diagnostic and state biomarker in bipolar disorder. First, messenger RNA levels of 19 candidate genes were assessed in peripheral blood mononuclear cells of 37 rapid cycling bipolar disorder patients in different affective states (depression, mania and euthymia) during a 6-12-month period and in 40 age...... subjects. In patients with bipolar disorder, upregulation of NDUFV2 was observed in a depressed state compared with a euthymic state. The composite gene expression measure for discrimination between patients and healthy control subjects on the basis of 19 genes generated an area under the receiver...

Wnt Signalling in Gastrointestinal Epithelial Stem Cells

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Dustin J. Flanagan

2018-03-01

Full Text Available Wnt signalling regulates several cellular functions including proliferation, differentiation, apoptosis and migration, and is critical for embryonic development. Stem cells are defined by their ability for self-renewal and the ability to be able to give rise to differentiated progeny. Consequently, they are essential for the homeostasis of many organs including the gastrointestinal tract. This review will describe the huge advances in our understanding of how stem cell functions in the gastrointestinal tract are regulated by Wnt signalling, including how deregulated Wnt signalling can hijack these functions to transform cells and lead to cancer.

Regulation of Cell Wall Biogenesis in Saccharomyces cerevisiae: The Cell Wall Integrity Signaling Pathway

Science.gov (United States)

Levin, David E.

2011-01-01

The yeast cell wall is a strong, but elastic, structure that is essential not only for the maintenance of cell shape and integrity, but also for progression through the cell cycle. During growth and morphogenesis, and in response to environmental challenges, the cell wall is remodeled in a highly regulated and polarized manner, a process that is principally under the control of the cell wall integrity (CWI) signaling pathway. This pathway transmits wall stress signals from the cell surface to the Rho1 GTPase, which mobilizes a physiologic response through a variety of effectors. Activation of CWI signaling regulates the production of various carbohydrate polymers of the cell wall, as well as their polarized delivery to the site of cell wall remodeling. This review article centers on CWI signaling in Saccharomyces cerevisiae through the cell cycle and in response to cell wall stress. The interface of this signaling pathway with other pathways that contribute to the maintenance of cell wall integrity is also discussed. PMID:22174182

Risk factors for suicide among children and youths with bipolar spectrum and early bipolar disorder.

Science.gov (United States)

Rajewska-Rager, Aleksandra; Sibilski, Piotr; Lepczyńska, Natalia

2015-01-01

In recent years much attention has been given to determine risk factors for suicide among adults with bipolar disorder. Such studies concerning children and youths, which would also take into account the specificity of the developmental age, are still too few. The ability to identify risk factors for children and youths with mood disorders, as well as the possibility to monitor them, is an essential element in preventing suicidal behaviours. Previous studies have clearly indicated that in the group of patients with an early onset of the bipolar disorder the occurrence of suicidal thoughts and intentions were significantly increased. Identifying the risk of suicide is hindered further by the complexity of the phenomenon, which is a compound interaction of various factors: biological, environmental, sociological, psychological and clinical. This is especially true with young adults suffering from mental illness and presenting a number of other psychopathological symptoms. The following paper introduces and reviews the results of current studies, which analysed the risk factors for suicide among children and youths with bipolar spectrum or already diagnosed with bipolar disorder. For this purpose we conducted the overview of recent years literature available in PubMed/MEDLINE database, including the following search criteria: early onset bipolar disorder, bipolar disorder in children and young people, the spectrum of bipolar disorder, and suicidal ideation, suicidal intent, suicide.

Lower switch rate in depressed patients with bipolar II than bipolar I disorder treated adjunctively with second-generation antidepressants

NARCIS (Netherlands)

Altshuler, LL; Suppes, T; Nolen, WA; Leverich, G; Keck, PE; Frye, MA; Kupka, R; McElroy, SL; Grunze, H; Kitchen, CMR; Post, R; Black, D.O.

Objectives: The authors compared the switch rate into hypomania/mania in depressed patients treated with second-generation antidepressants who had either bipolar I or bipolar II disorder. Method: In a 10-week trial, 184 outpatients with bipolar depression (134 with bipolar I disorder, 48 with

Bipolar Disorder and Early Affective Trauma.

Science.gov (United States)

de Codt, Aloise; Monhonval, Pauline; Bongaerts, Xavier; Belkacemi, Ikram; Tecco, Juan Martin

2016-09-01

Bipolar disorder is a chronic psychiatric disease with a high prevalence and is a major psychosocial and medical burden. The exact etiological pathways of bipolar disorder are not fully understood. Genetic factors are known to play an important role in the etiology of bipolar disorder. However, high rates of discordance among identical twins and a growing body of evidence that environmental factors such as early stress can influence the onset and course of psychiatric diseases underline the importance of additional etiological mechanisms of bipolar disorders. There has been little investigation about early trauma in bipolar disorder. The aim of this study was to review the literature on the association between early traumatic interactions like child neglect, mistreatment, abuse or early parental separation and the occurrence of bipolar disorder in adulthood or impact on the course of the disease. Studies investigating associations between child neglect, mistreatment, abuse or early parental separation and occurrence of bipolar disorder in adulthood or impact on the course of the disease were searched in the Pubmed database. More than 700 articles were sorted independently by two of the authors using predefined criteria. Only research articles, reviews and meta-analyses were selected for this review. 53 articles met the inclusion criteria. To date, four systematic reviews partially addressed our research question. Early trauma is more frequently found in the past of bipolar patients than in the general population. Studies support a harmful effect of childhood trauma on the course of bipolar disease, with more anxious, depressive or psychotic symptoms, an early age of onset and a worse prognosis. Early trauma is more often found in the past of bipolar adult patients than the general population and studies support a harmful effect of childhood trauma on the course of bipolar disease, with more anxious, depressive or psychotic symptoms, an early age of onset and a

Bipolar polaron pair recombination in polymer/fullerene solar cells

DEFF Research Database (Denmark)

Kupijai, Alexander J.; Behringer, Konstantin M.; Schaeble, Florian G.

2015-01-01

We present a study of the rate-limiting spin-dependent charge-transfer processes in different polymer/fullerene bulk-heterojunction solar cells at 10 K. Observing central spin-locking signals in pulsed electrically detected magnetic resonance and an inversion of Rabi oscillations in multifrequency...

Late Onset Bipolar Disorder: Case Report

OpenAIRE

Filipa Araújo; Adriana Horta

2016-01-01

Background: Bipolar disorder affects approximately 1% of the population, with diagnosis often being made during late adolescence and early adulthood, and only rarely (0.1%) in the elderly. Late onset bipolar disorder in the elderly has a impact on the nature and course of bipolar disorder. Aims: The authors report a case of bipolar disorder emerging in late life  (76years old) with no cleary identified organic cause. Conclusion: This case highlights the importance of a broad different...

Reconstruction and signal propagation analysis of the Syk signaling network in breast cancer cells.

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Aurélien Naldi

2017-03-01

Full Text Available The ability to build in-depth cell signaling networks from vast experimental data is a key objective of computational biology. The spleen tyrosine kinase (Syk protein, a well-characterized key player in immune cell signaling, was surprisingly first shown by our group to exhibit an onco-suppressive function in mammary epithelial cells and corroborated by many other studies, but the molecular mechanisms of this function remain largely unsolved. Based on existing proteomic data, we report here the generation of an interaction-based network of signaling pathways controlled by Syk in breast cancer cells. Pathway enrichment of the Syk targets previously identified by quantitative phospho-proteomics indicated that Syk is engaged in cell adhesion, motility, growth and death. Using the components and interactions of these pathways, we bootstrapped the reconstruction of a comprehensive network covering Syk signaling in breast cancer cells. To generate in silico hypotheses on Syk signaling propagation, we developed a method allowing to rank paths between Syk and its targets. We first annotated the network according to experimental datasets. We then combined shortest path computation with random walk processes to estimate the importance of individual interactions and selected biologically relevant pathways in the network. Molecular and cell biology experiments allowed to distinguish candidate mechanisms that underlie the impact of Syk on the regulation of cortactin and ezrin, both involved in actin-mediated cell adhesion and motility. The Syk network was further completed with the results of our biological validation experiments. The resulting Syk signaling sub-networks can be explored via an online visualization platform.

Cell signaling during Trypanosoma cruzi invasion

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Fernando Yukio Maeda

2012-11-01

Full Text Available Cell signaling is an essential requirement for mammalian cell invasion by Trypanosoma cruzi. Depending on the parasite strain and the parasite developmental form, distinct signaling pathways may be induced. In this short review, we focus on the data coming from studies with metacyclic trypomastigotes (MT generated in vitro and tissue culture-derived trypomastigotes (TCT, used as counterparts of insect-borne and bloodstream parasites respectively. During invasion of host cells by MT or TCT, intracellular Ca2+ mobilization and host cell lysosomal exocytosis are triggered. Invasion mediated by MT surface molecule gp82 requires the activation of mammalian target of rapamycin (mTOR, phosphatidylinositol 3-kinase (PI3K and protein kinase C (PKC in the host cell, associated with Ca2+-dependent disruption of the actin cytoskeleton. In MT, protein tyrosine kinase (PTK, PI3K, phospholipase C (PLC and PKC appear to be activated. TCT invasion, on the other hand, does not rely on mTOR activation, rather on target cell PI3K, and may involve the host cell autophagy for parasite internalization. Enzymes, such oligopeptidase B and the major T. cruzi cysteine proteinase cruzipain, have been shown to generate molecules that induce target cell Ca2+ signal. In addition, TCT may trigger host cell responses mediated by TGF-β receptor or integrin family member. Further investigations are needed for a more complete and detailed picture of T. cruzi invasion.

Bipolar outflow in B335

International Nuclear Information System (INIS)

Hirano, N.; Kameya, O.; Nakayama, M.; Takakubo, K.

1988-01-01

The high-velocity (C-12)O (J = 1-0) emission in B335 with a high angular resolution of 16 arcsec has been mapped. The high-velocity emission shows distinct bipolar pattern centered at IRAS 19345+0727, toward which a strong high-velocity (C-12)O emission has been detected. The bipolar lobes delineate remarkable collimation toward the IRAS source, indicating that the flow is focused within 0.02 pc of the driving source. Each lobe is accompanied by significant wing emission with the opposite velocity shift, which clearly shows the association with IRAS 19345+0727. This feature is well explained as a bipolar flow the axis of which is nearly perpendicular to the line of sight. There is no evidence of another evolved bipolar flow which does not associate with any dense core as previously suggested. This suggests that B335 is a site of very recent star formation, containing a single bipolar flow with an age of about 30,000 yr. 15 references

Influences of bipolar plate channel blockages on PEM fuel cell performances

International Nuclear Information System (INIS)

Heidary, Hadi; Kermani, Mohammad J.; Dabir, Bahram

2016-01-01

Highlights: • Effect of partial- or full-blockage of PEMFC flow channels is numerically studied. • The anode blockage does not show any positive effects on cell performance. • Full blockages, despite higher pressure drop, better enhance net electrical power. • Additions of blocks more than five do not improve the cell performance. • Full blockage of cathode channels with five blocks enhances the net power by 30%. - Abstract: In this paper, the effect of partial- or full-block placement along the flow channels of PEM fuel cells is numerically studied. Blockage in the channel of flow-field diverts the flow into the gas diffusion layer (GDL) and enhances the mass transport from the channel core part to the catalyst layer, which in turn improves the cell performance. By partial blockage, only a part of the channel flow is shut off. While in full blockage, in which the flow channel cross sections are fully blocked, the only avenue left for the continuation of the gas is to travel over the blocks via the porous zone (GDL). In this study, a 3D numerical model consisting of a 9-layer PEM fuel cell is performed. A wide spectrum of numerical studies is performed to study the influences of the number of blocks, blocks height, and anode/cathode-side flow channel blockage. The results show that the case of full blockage enhances the net electrical power more than that of the partial blockage, in spite of higher pressure drop. Performed studies show that full blockage of the cathode-side flow channels with five blocks along the 5 cm channel enhances the net power by 30%. The present work provides helpful guidelines to bipolar plate manufacturers.

C-reactive protein and white blood cell levels in schizophrenia, bipolar disorders and depression - associations with mortality and psychiatric outcomes

DEFF Research Database (Denmark)

Horsdal, H T; Köhler-Forsberg, O; Benros, Michael E

2017-01-01

BACKGROUND: Mental disorders have been associated with increased levels of inflammatory markers, which can affect disease trajectories. We aimed to assess levels of C-reactive protein (CRP) and white blood cells (WBC) across individuals with schizophrenia, bipolar disorder, and depression......, and to investigate associations with subsequent psychiatric admission and mortality. METHODS: We identified all adults in the Central Denmark Region during 2000-2012 with a first diagnosis of schizophrenia, bipolar disorder, or depression and a baseline measurement of CRP and/or WBC count. We followed.......5mg/L) (particularly during manic states, 3.9mg/L), followed by schizophrenia (3.1mg/L), and depression (2.8mg/L), while baseline WBC count did not differ (median 7.1×10(9)/L). Elevated CRP levels were associated with increased all-cause mortality by adjusted HRs of 1.56 (95% CI: 1.02-2.38) for levels...

BMP signaling regulates satellite cell-dependent postnatal muscle growth.

Science.gov (United States)

Stantzou, Amalia; Schirwis, Elija; Swist, Sandra; Alonso-Martin, Sonia; Polydorou, Ioanna; Zarrouki, Faouzi; Mouisel, Etienne; Beley, Cyriaque; Julien, Anaïs; Le Grand, Fabien; Garcia, Luis; Colnot, Céline; Birchmeier, Carmen; Braun, Thomas; Schuelke, Markus; Relaix, Frédéric; Amthor, Helge

2017-08-01

Postnatal growth of skeletal muscle largely depends on the expansion and differentiation of resident stem cells, the so-called satellite cells. Here, we demonstrate that postnatal satellite cells express components of the bone morphogenetic protein (BMP) signaling machinery. Overexpression of noggin in postnatal mice (to antagonize BMP ligands), satellite cell-specific knockout of Alk3 (the gene encoding the BMP transmembrane receptor) or overexpression of inhibitory SMAD6 decreased satellite cell proliferation and accretion during myofiber growth, and ultimately retarded muscle growth. Moreover, reduced BMP signaling diminished the adult satellite cell pool. Abrogation of BMP signaling in satellite cell-derived primary myoblasts strongly diminished cell proliferation and upregulated the expression of cell cycle inhibitors p21 and p57 In conclusion, these results show that BMP signaling defines postnatal muscle development by regulating satellite cell-dependent myofiber growth and the generation of the adult muscle stem cell pool. © 2017. Published by The Company of Biologists Ltd.

Bipolar mixed features - Results from the comparative effectiveness for bipolar disorder (Bipolar CHOICE) study.

Science.gov (United States)

Tohen, Mauricio; Gold, Alexandra K; Sylvia, Louisa G; Montana, Rebecca E; McElroy, Susan L; Thase, Michael E; Rabideau, Dustin J; Nierenberg, Andrew A; Reilly-Harrington, Noreen A; Friedman, Edward S; Shelton, Richard C; Bowden, Charles L; Singh, Vivek; Deckersbach, Thilo; Ketter, Terence A; Calabrese, Joseph R; Bobo, William V; McInnis, Melvin G

2017-08-01

DSM-5 changed the criteria from DSM-IV for mixed features in mood disorder episodes to include non-overlapping symptoms of depression and hypomania/mania. It is unknown if, by changing these criteria, the same group would qualify for mixed features. We assessed how those meeting DSM-5 criteria for mixed features compare to those meeting DSM-IV criteria. We analyzed data from 482 adult bipolar patients in Bipolar CHOICE, a randomized comparative effectiveness trial. Bipolar diagnoses were confirmed through the MINI International Neuropsychiatric Interview (MINI). Presence and severity of mood symptoms were collected with the Bipolar Inventory of Symptoms Scale (BISS) and linked to DSM-5 and DSM-IV mixed features criteria. Baseline demographics and clinical variables were compared between mood episode groups using ANOVA for continuous variables and chi-square tests for categorical variables. At baseline, the frequency of DSM-IV mixed episodes diagnoses obtained with the MINI was 17% and with the BISS was 20%. Using DSM-5 criteria, 9% of participants met criteria for hypomania/mania with mixed features and 12% met criteria for a depressive episode with mixed features. Symptom severity was also associated with increased mixed features with a high rate of mixed features in patients with mania/hypomania (63.8%) relative to those with depression (8.0%). Data on mixed features were collected at baseline only and thus do not reflect potential patterns in mixed features within this sample across the study duration. The DSM-5 narrower, non-overlapping definition of mixed episodes resulted in fewer patients who met mixed criteria compared to DSM-IV. Copyright © 2017. Published by Elsevier B.V.

Brief Report: A Family Risk Study Exploring Bipolar Spectrum Problems and Cognitive Biases in Adolescent Children of Bipolar Parents

Science.gov (United States)

Espie, Jonathan; Jones, Steven H.; Vance, Yvonne H.; Tai, Sara J.

2012-01-01

Children of parents with bipolar disorder are at increased risk of bipolar spectrum diagnoses. This cross-sectional study explores cognitive factors in the prediction of vulnerability to bipolar disorder. Adolescents at high-risk (with a parent with bipolar disorder; n = 23) and age and gender matched adolescents (n = 24) were recruited. Parent…

Three times more days depressed than manic or hypomanic in both bipolar I and bipolar II disorder

NARCIS (Netherlands)

Kupka, Ralph W.; Altshuler, Lori L.; Nolen, Willem A.; Suppes, Trisha; Luckenbaugh, David A.; Leverich, Gabriele S.; Frye, Mark A.; Keck, Paul E.; McElroy, Susan L.; Grunze, Heinz; Post, Robert M.

Objectives: To assess the proportion of time spent in mania, depression and euthymia in a large cohort of bipolar subjects studied longitudinally, and to investigate depression/mania ratios in patients with bipolar I versus bipolar II disorder. Methods: Clinician-adjusted self-ratings of mood were

A possible common basis for MDD, bipolar disorder and schizophrenia: Lessons from electrophysiology

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Goded eShahaf

2016-06-01

Full Text Available There is ample electrophysiological evidence of attention dysfunction in the EEG/ERP signal of various psychopathologies such as major depressive disorder (MDD, bipolar disorder, and schizophrenia. The reduced attention-related ERP waves show much similarity between MDD, bipolar disorder, and schizophrenia, raising the question whether there are similarities in the neurophysiologic process that underlies attention dysfunction in these pathologies. The present work suggests that there is such a unified underlying neurophysiologic process, which results in reduced attention in the three pathologies. Naturally, as these pathologies involve different clinical manifestations, we expect differences in their underlying neurophysiology. These differences and their subtle manifestation in the ERP marker for attention are also discussed.MDD, bipolar disorder and schizophrenia are just three of multiple neuropsychiatric disorders, which involve changes in the EEG/ERP manifestations of attention. Further work should expand the basic model presented here to offer comprehensive modeling of these multiple disorders and to emphasize similarities and dissimilarities of the underlying neurophysiologic processes.

Peripheral inflammation during abnormal mood states in bipolar I disorder.

Science.gov (United States)

Fiedorowicz, Jess G; Prossin, Alan R; Johnson, Casey P; Christensen, Gary E; Magnotta, Vincent A; Wemmie, John A

2015-11-15

Bipolar disorder carries a substantive morbidity and mortality burden, particularly related to cardiovascular disease. Abnormalities in peripheral inflammatory markers, which have been commonly reported in case-control studies, potentially link these co-morbidities. However, it is not clear whether inflammatory markers change episodically in response to mood states or are indicative of chronic pro-inflammatory activity, regardless of mood, in bipolar disorder. Investigations focused on comparing concentrations of specific inflammatory cytokines associated with immune activation status (primary outcome=tumor necrosis factor alpha (TNF-α)) in 37 participants with bipolar disorder across 3 mood states (mania N=15, depression N=9, normal mood N=13) and 29 controls without a psychiatric disorder (total N=66). Cytokine levels were also compared to T1ρ, a potential neuroimaging marker for inflammation, in select brain regions in a subsample (N=39). Participants with bipolar disorder and healthy controls did not differ significantly in inflammatory cytokine concentrations. However, compared to cases with normal mood, cases with abnormal mood states (mania and depression) had significantly elevated levels of TNF-α, its soluble receptors (sTNFR1/sTNFR2), other macrophage-derived cytokines (interleukin 1β (IL-1β), IL-6, IL-10, and IL-18) in addition to IL-4, interferon-γ, monocyte chemotactic protein-1, fibroblast growth factor β, and vascular endothelial growth factor. Cytokine levels were not correlated with signals from T1ρ imaging in selected structures (amygdalae, hippocampi, hypothalamus, anterior cingulate gyrus, and middle frontal gyrus). Participants were not followed prospectively across mood states. Activation of inflammatory markers was found in abnormal mood states of bipolar disorder. Longitudinal study of individuals with mood disorders is needed to confirm these findings and to elucidate the time course of any such changes. Copyright © 2015 Elsevier B

Apoptotic Cells Induced Signaling for Immune Homeostasis in Macrophages and Dendritic Cells

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Uriel Trahtemberg

2017-10-01

Full Text Available Inefficient and abnormal clearance of apoptotic cells (efferocytosis contributes to systemic autoimmune disease in humans and mice, and inefficient chromosomal DNA degradation by DNAse II leads to systemic polyarthritis and a cytokine storm. By contrast, efficient clearance allows immune homeostasis, generally leads to a non-inflammatory state for both macrophages and dendritic cells (DCs, and contributes to maintenance of peripheral tolerance. As many as 3 × 108 cells undergo apoptosis every hour in our bodies, and one of the primary “eat me” signals expressed by apoptotic cells is phosphatidylserine (PtdSer. Apoptotic cells themselves are major contributors to the “anti-inflammatory” nature of the engulfment process, some by secreting thrombospondin-1 (TSP-1 or adenosine monophosphate and possibly other immune modulating “calm-down” signals that interact with macrophages and DCs. Apoptotic cells also produce “find me” and “tolerate me” signals to attract and immune modulate macrophages and DCs that express specific receptors for some of these signals. Neither macrophages nor DCs are uniform, and each cell type may variably express membrane proteins that function as receptors for PtdSer or for opsonins like complement or opsonins that bind to PtdSer, such as protein S and growth arrest-specific 6. Macrophages and DCs also express scavenger receptors, CD36, and integrins that function via bridging molecules such as TSP-1 or milk fat globule-EGF factor 8 protein and that differentially engage in various multi-ligand interactions between apoptotic cells and phagocytes. In this review, we describe the anti-inflammatory and pro-homeostatic nature of apoptotic cell interaction with the immune system. We do not review some forms of immunogenic cell death. We summarize the known apoptotic cell signaling events in macrophages and DCs that are related to toll-like receptors, nuclear factor kappa B, inflammasome, the lipid

Vectorial signalling mechanism required for cell-cell communication during sporulation in Bacillus subtilis.

Science.gov (United States)

Diez, Veronica; Schujman, Gustavo E; Gueiros-Filho, Frederico J; de Mendoza, Diego

2012-01-01

Spore formation in Bacillus subtilis takes place in a sporangium consisting of two chambers, the forespore and the mother cell, which are linked by pathways of cell-cell communication. One pathway, which couples the proteolytic activation of the mother cell transcription factor σ(E) to the action of a forespore synthesized signal molecule, SpoIIR, has remained enigmatic. Signalling by SpoIIR requires the protein to be exported to the intermembrane space between forespore and mother cell, where it will interact with and activate the integral membrane protease SpoIIGA. Here we show that SpoIIR signal activity as well as the cleavage of its N-terminal extension is strictly dependent on the prespore fatty acid biosynthetic machinery. We also report that a conserved threonine residue (T27) in SpoIIR is required for processing, suggesting that signalling of SpoIIR is dependent on fatty acid synthesis probably because of acylation of T27. In addition, SpoIIR localization in the forespore septal membrane depends on the presence of SpoIIGA. The orchestration of σ(E) activation in the intercellular space by an acylated signal protein provides a new paradigm to ensure local transmission of a weak signal across the bilayer to control cell-cell communication during development. © 2011 Blackwell Publishing Ltd.

Quetiapine monotherapy for bipolar depression

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Michael E Thase

2008-03-01

Full Text Available Michael E ThaseDepartments of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; the Philadelphia Veterans Affairs Medical Center, Philadelphia, PA, USA; and the University of Pittsburgh Medical Center, Pittsburgh, PA, USAAbstract: Bipolar depression is more common, disabling, and difficult-to-treat than the manic and hypomanic phases that define bipolar disorder. Unlike the treatment of so-called “unipolar” depressions, antidepressants generally are not indicated as monotherapies for bipolar depressions and recent studies suggest that - even when used in combination with traditional mood stabilizers – antidepressants may have questionable value for bipolar depression. The current practice is that mood stabilizers are initiated first as monotherapies; however, the antidepressant efficacy of lithium and valproate is modest at best. Within this context the role of atypical antipsychotics is being evaluated. The combination of olanzapine and the antidepressant fluoxetine was the first treatment to receive regulatory approval in the US specifically for bipolar I depression. Quetiapine was the second medication to be approved for this indication, largely as the result of two pivotal trials known by the acronyms of BOLDER (BipOLar DEpRession I and II. Both studies demonstrated that two doses of quetiapine (300 mg and 600 mg given once daily at bedtime were significantly more effective than placebo, with no increased risk of patients switching into mania. Pooling the two studies, quetiapine was effective for both bipolar I and bipolar II depressions and for patients with (and without a history of rapid cycling. The two doses were comparably effective in both studies. Although the efficacy of quetiapine monotherapy has been established, much additional research is necessary. Further studies are needed to more fully investigate dose-response relationships and comparing quetiapine monotherapy to other mood stabilizers

Chemokines: a new dendritic cell signal for T cell activation

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Christoph A Thaiss

2011-08-01

Full Text Available Dendritic cells (DCs are the main inducers and regulators of cytotoxic T lymphocyte (CTL responses against viruses and tumors. One checkpoint to avoid misguided CTL activation, which might damage healthy cells of the body, is the necessity for multiple activation signals, involving both antigenic as well as additional signals that reflect the presence of pathogens. DCs provide both signals when activated by ligands of pattern recognition receptors and licensed by helper lymphocytes. Recently, it has been established that such T cell licensing can be facilitated by CD4+ T helper cells (classical licensing or by NKT cells (alternative licensing. Licensing regulates the DC/CTL cross-talk at multiple layers. Direct recruitment of CTLs through chemokines released by licensed DCs has recently emerged as a common theme and has a crucial impact on the efficiency of CTL responses. Here, we discuss recent advances in our understanding of DC licensing for cross-priming and implications for the temporal and spatial regulation underlying this process. Future vaccination strategies will benefit from a deeper insight into the mechanisms that govern CTL activation.

A new bipolar RRAM selector based on anti-parallel connected diodes for crossbar applications

International Nuclear Information System (INIS)

Li, Yingtao; Gong, Qingchun; Li, Rongrong; Jiang, Xinyu

2014-01-01

Crossbar arrays are the most promising application of a resistive random access memory (RRAM) device for achieving high density memory. However, cross-talk interference in the crossbar array limits the increase in the integration density. In this paper, the combination of two anti-parallel connected diodes and a bipolar RRAM cell is proposed to suppress the sneak current in a crossbar array with anti-parallel connected diodes as the selector for the bipolar RRAM. By using the anti-parallel connected diodes as a selector, the sneak current can be effectively suppressed and the high density crossbar array of more than 1 Mb can be realized as estimated by the 1/2V read voltage scheme. These results indicate that anti-parallel connected diodes can be used as a bipolar selector and have great potential for high density bipolar RRAM crossbar array applications. (papers)

Development of new bi-polar plates based on electrically conductive filled polymers for PEMFC

Energy Technology Data Exchange (ETDEWEB)

Jousse, F.; Salas, J.F.; Giroud, F. [C.E.A., Le Ripault, Monts (France); Icard, B.; Laurent, J.Y.; Serre Combe, P.

2000-07-01

In polymer electrolyte membrane fuel cell technology, the bi-polar plates are dedicated to: the current collection, the separation and distribution of gas (hydrogen and oxygen) at the cathode and the anode. To achieve these functions, bi-polar plate materials must satisfy the following properties: high conductivity (higher than 10 S/cm), high chemical resistance to acid and water, very low permeability to hydrogen (permeability < Pe{sup H2}{sub Nafion} (20 C) = 7.10{sup -17} m{sup 2}/Pa/s). Traditionally bi-polar plates have been designed with stainless steel or graphite. However, the cost of these plates are incompatible to transport applications, principally because of the gas channel machining step. Recently, we have noticed the work of T.M. Besmann [1] on the manufacturing of bi-polar plates based on carbon fibres and phenolic resin, processed by pyrolisis and densification on surface by a chemical vapour infiltration process. However, this kind of process seems too expensive and complex for the needs of the road electric transportation industry. Organic composites based on conductive chemical resistant fillers and processed by molding could be an alternative solution. Bi-polar plates requirements can be achieved by controlling and optimising experimental parameters such as the nature and morphology of fillers, the resin characteristics, and the process conditions. To avoid corrosion of the composite material, and then, the contamination of the cell, we have selected non metallic fillers, based on graphite or carbon black. (orig.)

Probing Embryonic Stem Cell Autocrine and Paracrine Signaling Using Microfluidics

Science.gov (United States)

Przybyla, Laralynne; Voldman, Joel

2012-07-01

Although stem cell fate is traditionally manipulated by exogenously altering the cells' extracellular signaling environment, the endogenous autocrine and paracrine signals produced by the cells also contribute to their two essential processes: self-renewal and differentiation. Autocrine and/or paracrine signals are fundamental to both embryonic stem cell self-renewal and early embryonic development, but the nature and contributions of these signals are often difficult to fully define using conventional methods. Microfluidic techniques have been used to explore the effects of cell-secreted signals by controlling cell organization or by providing precise control over the spatial and temporal cellular microenvironment. Here we review how such techniques have begun to be adapted for use with embryonic stem cells, and we illustrate how many remaining questions in embryonic stem cell biology could be addressed using microfluidic technologies.

Cytoskeleton in Mast Cell Signaling

Science.gov (United States)

Dráber, Pavel; Sulimenko, Vadym; Dráberová, Eduarda

2012-01-01

Mast cell activation mediated by the high affinity receptor for IgE (FcεRI) is a key event in allergic response and inflammation. Other receptors on mast cells, as c-Kit for stem cell factor and G protein-coupled receptors (GPCRs) synergistically enhance the FcεRI-mediated release of inflammatory mediators. Activation of various signaling pathways in mast cells results in changes in cell morphology, adhesion to substrate, exocytosis, and migration. Reorganization of cytoskeleton is pivotal in all these processes. Cytoskeletal proteins also play an important role in initial stages of FcεRI and other surface receptors induced triggering. Highly dynamic microtubules formed by αβ-tubulin dimers as well as microfilaments build up from polymerized actin are affected in activated cells by kinases/phosphatases, Rho GTPases and changes in concentration of cytosolic Ca2+. Also important are nucleation proteins; the γ-tubulin complexes in case of microtubules or Arp 2/3 complex with its nucleation promoting factors and formins in case of microfilaments. The dynamic nature of microtubules and microfilaments in activated cells depends on many associated/regulatory proteins. Changes in rigidity of activated mast cells reflect changes in intermediate filaments build up from vimentin. This review offers a critical appraisal of current knowledge on the role of cytoskeleton in mast cells signaling. PMID:22654883

Role of Notch signaling in cell-fate determination of human mammary stem/progenitor cells

International Nuclear Information System (INIS)

Dontu, Gabriela; Jackson, Kyle W; McNicholas, Erin; Kawamura, Mari J; Abdallah, Wissam M; Wicha, Max S

2004-01-01

Notch signaling has been implicated in the regulation of cell-fate decisions such as self-renewal of adult stem cells and differentiation of progenitor cells along a particular lineage. Moreover, depending on the cellular and developmental context, the Notch pathway acts as a regulator of cell survival and cell proliferation. Abnormal expression of Notch receptors has been found in different types of epithelial metaplastic lesions and neoplastic lesions, suggesting that Notch may act as a proto-oncogene. The vertebrate Notch1 and Notch4 homologs are involved in normal development of the mammary gland, and mutated forms of these genes are associated with development of mouse mammary tumors. In order to determine the role of Notch signaling in mammary cell-fate determination, we have utilized a newly described in vitro system in which mammary stem/progenitor cells can be cultured in suspension as nonadherent 'mammospheres'. Notch signaling was activated using exogenous ligands, or was inhibited using previously characterized Notch signaling antagonists. Utilizing this system, we demonstrate that Notch signaling can act on mammary stem cells to promote self-renewal and on early progenitor cells to promote their proliferation, as demonstrated by a 10-fold increase in secondary mammosphere formation upon addition of a Notch-activating DSL peptide. In addition to acting on stem cells, Notch signaling is also able to act on multipotent progenitor cells, facilitating myoepithelial lineage-specific commitment and proliferation. Stimulation of this pathway also promotes branching morphogenesis in three-dimensional Matrigel cultures. These effects are completely inhibited by a Notch4 blocking antibody or a gamma secretase inhibitor that blocks Notch processing. In contrast to the effects of Notch signaling on mammary stem/progenitor cells, modulation of this pathway has no discernable effect on fully committed, differentiated, mammary epithelial cells. These studies

Cross Entropy Measures of Bipolar and Interval Bipolar Neutrosophic Sets and Their Application for Multi-Attribute Decision-Making

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Surapati Pramanik

2018-03-01

Full Text Available The bipolar neutrosophic set is an important extension of the bipolar fuzzy set. The bipolar neutrosophic set is a hybridization of the bipolar fuzzy set and neutrosophic set. Every element of a bipolar neutrosophic set consists of three independent positive membership functions and three independent negative membership functions. In this paper, we develop cross entropy measures of bipolar neutrosophic sets and prove their basic properties. We also define cross entropy measures of interval bipolar neutrosophic sets and prove their basic properties. Thereafter, we develop two novel multi-attribute decision-making strategies based on the proposed cross entropy measures. In the decision-making framework, we calculate the weighted cross entropy measures between each alternative and the ideal alternative to rank the alternatives and choose the best one. We solve two illustrative examples of multi-attribute decision-making problems and compare the obtained result with the results of other existing strategies to show the applicability and effectiveness of the developed strategies. At the end, the main conclusion and future scope of research are summarized.

AlliedSignal solid oxide fuel cell technology

Energy Technology Data Exchange (ETDEWEB)

Minh, N.; Barr, K.; Kelly, P.; Montgomery, K. [AlliedSignal Aerospace Equipment Systems, Torrance, CA (United States)

1996-12-31

AlliedSignal has been developing high-performance, lightweight solid oxide fuel cell (SOFC) technology for a broad spectrum of electric power generation applications. This technology is well suited for use in a variety of power systems, ranging from commercial cogeneration to military mobile power sources. The AlliedSignal SOFC is based on stacking high-performance thin-electrolyte cells with lightweight metallic interconnect assemblies to form a compact structure. The fuel cell can be operated at reduced temperatures (600{degrees} to 800{degrees}C). SOFC stacks based on this design has the potential of producing 1 kW/kg and 1 ML. This paper summarizes the technical status of the design, manufacture, and operation of AlliedSignal SOFCs.

Laminated exfoliated graphite composite-metal compositions for fuel cell flow field plate or bipolar plate applications

Science.gov (United States)

Zhamu, Aruna; Shi, Jinjun; Guo, Jiusheng; Jang, Bor Z

2014-05-20

An electrically conductive laminate composition for fuel cell flow field plate or bipolar plate applications. The laminate composition comprises at least a thin metal sheet having two opposed exterior surfaces and a first exfoliated graphite composite sheet bonded to the first of the two exterior surfaces of the metal sheet wherein the exfoliated graphite composite sheet comprises: (a) expanded or exfoliated graphite and (b) a binder or matrix material to bond the expanded graphite for forming a cohered sheet, wherein the binder or matrix material is between 3% and 60% by weight based on the total weight of the first exfoliated graphite composite sheet. Preferably, the first exfoliated graphite composite sheet further comprises particles of non-expandable graphite or carbon in the amount of between 3% and 60% by weight based on the total weight of the non-expandable particles and the expanded graphite. Further preferably, the laminate comprises a second exfoliated graphite composite sheet bonded to the second surface of the metal sheet to form a three-layer laminate. Surface flow channels and other desired geometric features can be built onto the exterior surfaces of the laminate to form a flow field plate or bipolar plate. The resulting laminate has an exceptionally high thickness-direction conductivity and excellent resistance to gas permeation.

RBX2 maintains final retinal cell position in a DAB1-dependent and -independent fashion.

Science.gov (United States)

Fairchild, Corinne L; Hino, Keiko; Han, Jisoo S; Miltner, Adam M; Peinado Allina, Gabriel; Brown, Caileigh E; Burns, Marie E; La Torre, Anna; Simó, Sergi

2018-02-02

The laminated structure of the retina is fundamental for the organization of the synaptic circuitry that translates light input into patterns of action potentials. However, the molecular mechanisms underlying cell migration and layering of the retina are poorly understood. Here, we show that RBX2, a core component of the E3 ubiquitin ligase CRL5, is essential for retinal layering and function. RBX2 regulates the final cell position of rod bipolar cells, cone photoreceptors and Muller glia. Our data indicate that sustained RELN/DAB1 signaling, triggered by depletion of RBX2 or SOCS7 - a CRL5 substrate adaptor known to recruit DAB1 - causes rod bipolar cell misposition. Moreover, whereas SOCS7 also controls Muller glia cell lamination, it is not responsible for cone photoreceptor positioning, suggesting that RBX2, most likely through CRL5 activity, controls other signaling pathways required for proper cone localization. Furthermore, RBX2 depletion reduces the number of ribbon synapses and disrupts cone photoreceptor function. Together, these results uncover RBX2 as a crucial molecular regulator of retina morphogenesis and cone photoreceptor function. © 2018. Published by The Company of Biologists Ltd.

Surface code—biophysical signals for apoptotic cell clearance

International Nuclear Information System (INIS)

Biermann, Mona; Maueröder, Christian; Brauner, Jan M; Chaurio, Ricardo; Herrmann, Martin; Muñoz, Luis E; Janko, Christina

2013-01-01

Apoptotic cell death and the clearance of dying cells play an important and physiological role in embryonic development and normal tissue turnover. In contrast to necrosis, apoptosis proceeds in an anti-inflammatory manner. It is orchestrated by the timed release and/or exposure of so-called ‘find-me’, ‘eat me’ and ‘tolerate me’ signals. Mononuclear phagocytes are attracted by various ‘find-me’ signals, including proteins, nucleotides, and phospholipids released by the dying cell, whereas the involvement of granulocytes is prevented via ‘stay away’ signals. The exposure of anionic phospholipids like phosphatidylserine (PS) by apoptotic cells on the outer leaflet of the plasma membrane is one of the main ‘eat me’ signals. PS is recognized by a number of innate receptors as well as by soluble bridging molecules on the surface of phagocytes. Importantly, phagocytes are able to discriminate between viable and apoptotic cells both exposing PS. Due to cytoskeleton remodeling PS has a higher lateral mobility on the surfaces of apoptotic cells thereby promoting receptor clustering on the phagocyte. PS not only plays an important role in the engulfment process, but also acts as ‘tolerate me’ signal inducing the release of anti-inflammatory cytokines by phagocytes. An efficient and fast clearance of apoptotic cells is required to prevent secondary necrosis and leakage of intracellular danger signals into the surrounding tissue. Failure or prolongation of the clearance process leads to the release of intracellular antigens into the periphery provoking inflammation and development of systemic inflammatory autoimmune disease like systemic lupus erythematosus. Here we review the current findings concerning apoptosis-inducing pathways, important players of apoptotic cell recognition and clearance as well as the role of membrane remodeling in the engulfment of apoptotic cells by phagocytes. (paper)

Cytokine signalling in embryonic stem cells

DEFF Research Database (Denmark)

Kristensen, David Møbjerg; Kalisz, Mark; Nielsen, Jens Høiriis

2006-01-01

Cytokines play a central role in maintaining self-renewal in mouse embryonic stem (ES) cells through a member of the interleukin-6 type cytokine family termed leukemia inhibitory factor (LIF). LIF activates the JAK-STAT3 pathway through the class I cytokine receptor gp130, which forms a trimeric...... pathways seem to converge on c-myc as a common target to promote self-renewal. Whereas LIF does not seem to stimulate self-renewal in human embryonic stem cells it cannot be excluded that other cytokines are involved. The pleiotropic actions of the increasing number of cytokines and receptors signalling...... via JAKs, STATs and SOCS exhibit considerable redundancy, compensation and plasticity in stem cells in accordance with the view that stem cells are governed by quantitative variations in strength and duration of signalling events known from other cell types rather than qualitatively different stem...

Adipocyte activation of cancer stem cell signaling in breast cancer

Institute of Scientific and Technical Information of China (English)

Benjamin; Wolfson; Gabriel; Eades; Qun; Zhou

2015-01-01

Signaling within the tumor microenvironment has a critical role in cancer initiation and progression. Adipocytes, one of the major components of the breast microenvironment,have been shown to provide pro-tumorigenic signals that promote cancer cell proliferation and invasiveness in vitro and tumorigenicity in vivo. Adipocyte secreted factors such as leptin and interleukin-6(IL-6) have a paracrine effect on breast cancer cells. In adipocyte-adjacent breast cancer cells, the leptin and IL-6 signaling pathways activate janus kinase 2/signal transducer and activatorof transcription 5, promoting the epithelial-mesenchymal transition, and upregulating stemness regulators such as Notch, Wnt and the Sex determining region Y-box 2/octamer binding transcription factor 4/Nanog signaling axis. In this review we will summarize the major signaling pathways that regulate cancer stem cells in breast cancer and describe the effects that adipocyte secreted IL-6 and leptin have on breast cancer stem cell signaling. Finally we will introduce a new potential treatment paradigm of inhibiting the adipocyte-breast cancer cell signaling via targeting the IL-6 or leptin pathways.

mTOR signaling promotes foam cell formation and inhibits foam cell egress through suppressing the SIRT1 signaling pathway.

Science.gov (United States)

Zheng, Haixiang; Fu, Yucai; Huang, Yusheng; Zheng, Xinde; Yu, Wei; Wang, Wei

2017-09-01

Atherosclerosis (AS) is a chronic immuno‑inflammatory disease accompanied by dyslipidemia. The authors previously demonstrated that sirtuin 1 (SIRT1) may prevent atherogenesis through influencing the liver X receptor/C‑C chemokine receptor type 7/nuclear factor‑κB (LXR‑CCR7/NF‑κB) signaling pathway. Previous studies have suggested a role for mammalian target of rapamycin (mTOR) signaling in the pathogenesis of cardiovascular diseases. The present study investigated the potential association between mTOR signaling and SIRT1‑LXR‑CCR7/NF‑κB signaling (SIRT1 signaling) in AS pathogenesis. To induce foam cell formation, U937 cells were differentiated into macrophages by exposure to phorbol 12‑myristate 13‑acetate (PMA) for 24 h, followed by treatment with palmitate and oxidized low density lipoprotein for a further 24 h. Oil red O staining revealed a large accumulation of lipid droplets present in foam cells. Western blot analysis demonstrated increased protein levels of phosphorylated (p)‑mTOR and its downstream factor p‑ribosomal protein S6 kinase (p70S6K). Reverse transcription‑quantitative polymerase chain reaction and western blot analyses additionally revealed decreased expression of SIRT1, LXRα and CCR7 and increased expression of NF‑κB and its downstream factor tumor necrosis factor‑α (TNF‑α) in an atherogenetic condition induced by lysophosphatidic acid (LPA). In addition, abundant lipid droplets accumulated in U937‑LPA‑treated foam cells. Rapamycin, an mTOR inhibitor, suppressed the expression and activity of mTOR and p70S6K, however enhanced expression of SIRT1, LXRα, and CCR7. Conversely, rapamycin deceased TNF‑α and NF‑κB activity, the latter of which was further confirmed by immunofluorescence analysis demonstrating increased levels of NF‑κB present in the cytoplasm compared with the nucleus. The findings of the present study suggest that mTOR signaling promotes foam cell formation and inhibits foam

Prediction of transition from common adolescent bipolar experiences to bipolar disorder: 10-year study.

Science.gov (United States)

Tijssen, Marijn J A; van Os, Jim; Wittchen, Hans-Ulrich; Lieb, Roselind; Beesdo, Katja; Mengelers, Ron; Wichers, Marieke

2010-02-01

Although (hypo)manic symptoms are common in adolescence, transition to adult bipolar disorder is infrequent. To examine whether the risk of transition to bipolar disorder is conditional on the extent of persistence of subthreshold affective phenotypes. In a 10-year prospective community cohort study of 3021 adolescents and young adults, the association between persistence of affective symptoms over 3 years and the 10-year clinical outcomes of incident DSM-IV (hypo)manic episodes and incident use of mental healthcare was assessed. Transition to clinical outcome was associated with persistence of symptoms in a dose-dependent manner. Around 30-40% of clinical outcomes could be traced to prior persistence of affective symptoms. In a substantial proportion of individuals, onset of clinical bipolar disorder may be seen as the poor outcome of a developmentally common and usually transitory non-clinical bipolar phenotype.

Alcoholism and anxiety in bipolar illness : Differential lifetime anxiety comorbidity in bipolar I women with and without alcoholism

NARCIS (Netherlands)

Levander, Eric; Frye, Mark A.; McElroy, Susan; Suppes, Trisha; Grunze, Heinz; Nolen, Willem A.; Kupka, Ralph; Keck, Paul E.; Leverich, Gabriele S.; Altshuler, Lori L.; Hwang, Sun; Mintz, Jim; Post, Robert M.

Introduction: This study was undertaken to evaluate the prevalence rate of anxiety comorbidity in bipolar subjects with and without alcohol use disorders (AUD). Methods: Bipolar men and women who entered the Stanley Foundation Bipolar Network (SFBN) underwent a Structured Clinical Interview for

"Is it menopause or bipolar?": a qualitative study of the experience of menopause for women with bipolar disorder.

Science.gov (United States)

Perich, Tania; Ussher, Jane; Parton, Chloe

2017-11-16

Menopause can be a time of change for women and may be marked by disturbances in mood. For women living with a mental illness, such as bipolar disorder, little is known about how they experience mood changes during menopause. This study aimed to explore how women with bipolar disorder constructed mood changes during menopause and how this impacted on treatment decisions. Semi-structured interviews were undertaken with fifteen women who reported they had been diagnosed with bipolar disorder. Data was analysed using thematic analysis guided by a social constructionist framework. Themes identified included 'Constructions of mood change: menopause or bipolar disorder?',' Life events, bipolar disorder and menopause coming together'; 'Treatment choices for mood change during menopause'. The accounts suggested that women related to the experience of mood changes during menopause through the lens of their existing framework of bipolar disorder, with implications for understanding of self and treatment choices.

Cellular Architecture Regulates Collective Calcium Signaling and Cell Contractility.

Directory of Open Access Journals (Sweden)

Jian Sun

2016-05-01

Full Text Available A key feature of multicellular systems is the ability of cells to function collectively in response to external stimuli. However, the mechanisms of intercellular cell signaling and their functional implications in diverse vascular structures are poorly understood. Using a combination of computational modeling and plasma lithography micropatterning, we investigate the roles of structural arrangement of endothelial cells in collective calcium signaling and cell contractility. Under histamine stimulation, endothelial cells in self-assembled and microengineered networks, but not individual cells and monolayers, exhibit calcium oscillations. Micropatterning, pharmacological inhibition, and computational modeling reveal that the calcium oscillation depends on the number of neighboring cells coupled via gap junctional intercellular communication, providing a mechanistic basis of the architecture-dependent calcium signaling. Furthermore, the calcium oscillation attenuates the histamine-induced cytoskeletal reorganization and cell contraction, resulting in differential cell responses in an architecture-dependent manner. Taken together, our results suggest that endothelial cells can sense and respond to chemical stimuli according to the vascular architecture via collective calcium signaling.

Stem cell signaling. An integral program for tissue renewal and regeneration : Wnt signaling and stem cell control

NARCIS (Netherlands)

Clevers, Hans; Loh, Kyle M; Nusse, Roel

2014-01-01

Stem cells fuel tissue development, renewal, and regeneration, and these activities are controlled by the local stem cell microenvironment, the "niche." Wnt signals emanating from the niche can act as self-renewal factors for stem cells in multiple mammalian tissues. Wnt proteins are lipid-modified,

Modeling suicide in bipolar disorders.

Science.gov (United States)

Malhi, Gin S; Outhred, Tim; Das, Pritha; Morris, Grace; Hamilton, Amber; Mannie, Zola

2018-02-19

Suicide is a multicausal human behavior, with devastating and immensely distressing consequences. Its prevalence is estimated to be 20-30 times greater in patients with bipolar disorders than in the general population. The burden of suicide and its high prevalence in bipolar disorders make it imperative that our current understanding be improved to facilitate prediction of suicide and its prevention. In this review, we provide a new perspective on the process of suicide in bipolar disorder, in the form of a novel integrated model that is derived from extant knowledge and recent evidence. A literature search of articles on suicide in bipolar disorder was conducted in recognized databases such as Scopus, PubMed, and PsycINFO using the keywords "suicide", "suicide in bipolar disorders", "suicide process", "suicide risk", "neurobiology of suicide" and "suicide models". Bibliographies of identified articles were further scrutinized for papers and book chapters of relevance. Risk factors for suicide in bipolar disorders are well described, and provide a basis for a framework of epigenetic mechanisms, moderated by neurobiological substrates, neurocognitive functioning, and social inferences within the environment. Relevant models and theories include the diathesis-stress model, the bipolar model of suicide and the ideation-to-action models, the interpersonal theory of suicide, the integrated motivational-volitional model, and the three-step theory. Together, these models provide a basis for the generation of an integrated model that illuminates the suicidal process, from ideation to action. Suicide is complex, and it is evident that a multidimensional and integrated approach is required to reduce its prevalence. The proposed model exposes and provides access to components of the suicide process that are potentially measurable and may serve as novel and specific therapeutic targets for interventions in the context of bipolar disorder. Thus, this model is useful not only

Basolateral BMP signaling in polarized epithelial cells.

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Masao Saitoh

Full Text Available Bone morphogenetic proteins (BMPs regulate various biological processes, mostly mediated by cells of mesenchymal origin. However, the roles of BMPs in epithelial cells are poorly understood. Here, we demonstrate that, in polarized epithelial cells, BMP signals are transmitted from BMP receptor complexes exclusively localized at the basolateral surface of the cell membrane. In addition, basolateral stimulation with BMP increased expression of components of tight junctions and enhanced the transepithelial resistance (TER, counteracting reduction of TER by treatment with TGF-β or an anti-tumor drug. We conclude that BMPs maintain epithelial polarity via intracellular signaling from basolaterally localized BMP receptors.

Depression and Bipolar Support Alliance

Science.gov (United States)

Depression and Bipolar Support Alliance Crisis Hotline Information Coping with a Crisis Suicide Prevention Information Psychiatric Hospitalization ... sign-up Education info, training, events Mood Disorders Depression Bipolar Disorder Anxiety Screening Center Co-occurring Illnesses/ ...

Late Onset Bipolar Disorder: Case Report

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Filipa Araújo

2016-07-01

Full Text Available Background: Bipolar disorder affects approximately 1% of the population, with diagnosis often being made during late adolescence and early adulthood, and only rarely (0.1% in the elderly. Late onset bipolar disorder in the elderly has a impact on the nature and course of bipolar disorder. Aims: The authors report a case of bipolar disorder emerging in late life  (76years old with no cleary identified organic cause. Conclusion: This case highlights the importance of a broad differential diagnosis and pharmacologic management when approaching new-onset manic/depressive symptoms among geriatric patients.

Photostable bipolar fluorescent probe for video tracking plasma membranes related cellular processes.

Science.gov (United States)

Zhang, Xinfu; Wang, Chao; Jin, Liji; Han, Zhuo; Xiao, Yi

2014-08-13

Plasma membranes can sense the stimulations and transmit the signals from extracellular environment and then make further responses through changes in locations, shapes or morphologies. Common fluorescent membrane markers are not well suited for long time tracking due to their shorter retention time inside plasma membranes and/or their lower photostability. To this end, we develop a new bipolar marker, Mem-SQAC, which can stably insert into plasma membranes of different cells and exhibits a long retention time over 30 min. Mem-SQAC also inherits excellent photostability from the BODIPY dye family. Large two-photon absorption cross sections and long wavelength fluorescence emissions further enhance the competitiveness of Mem-SQAC as a membrane marker. By using Mem-SQAC, significant morphological changes of plasma membranes have been monitored during heavy metal poisoning and drug induced apoptosis of MCF-7 cells; the change tendencies are so distinctly different from each other that they can be used as indicators to distinguish different cell injuries. Further on, the complete processes of endocytosis toward Staphylococcus aureus and Escherichia coli by RAW 264.7 cells have been dynamically tracked. It is discovered that plasma membranes take quite different actions in response to the two bacteria, information unavailable in previous research reports.

Redox signaling during hypoxia in mammalian cells

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Kimberly A. Smith

2017-10-01

Full Text Available Hypoxia triggers a wide range of protective responses in mammalian cells, which are mediated through transcriptional and post-translational mechanisms. Redox signaling in cells by reactive oxygen species (ROS such as hydrogen peroxide (H2O2 occurs through the reversible oxidation of cysteine thiol groups, resulting in structural modifications that can change protein function profoundly. Mitochondria are an important source of ROS generation, and studies reveal that superoxide generation by the electron transport chain increases during hypoxia. Other sources of ROS, such as the NAD(PH oxidases, may also generate oxidant signals in hypoxia. This review considers the growing body of work indicating that increased ROS signals during hypoxia are responsible for regulating the activation of protective mechanisms in diverse cell types.

Natural killer cell signal integration balances synapse symmetry and migration.

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Fiona J Culley

2009-07-01

Full Text Available Natural killer (NK cells discern the health of other cells by recognising the balance of activating and inhibitory ligands expressed by each target cell. However, how the integration of activating and inhibitory signals relates to formation of the NK cell immune synapse remains a central question in our understanding of NK cell recognition. Here we report that ligation of LFA-1 on NK cells induced asymmetrical cell spreading and migration. In contrast, ligation of the activating receptor NKG2D induced symmetrical spreading of ruffled lamellipodia encompassing a dynamic ring of f-actin, concurrent with polarization towards a target cell and a "stop" signal. Ligation of both LFA-1 and NKG2D together resulted in symmetrical spreading but co-ligation of inhibitory receptors reverted NK cells to an asymmetrical migratory configuration leading to inhibitory synapses being smaller and more rapidly disassembled. Using micropatterned activating and inhibitory ligands, signals were found to be continuously and locally integrated during spreading. Together, these data demonstrate that NK cells spread to form large, stable, symmetrical synapses if activating signals dominate, whereas asymmetrical migratory "kinapses" are favoured if inhibitory signals dominate. This clarifies how the integration of activating and inhibitory receptor signals is translated to an appropriate NK cell response.

Robustness of MEK-ERK Dynamics and Origins of Cell-to-Cell Variability in MAPK Signaling

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Sarah Filippi

2016-06-01

Full Text Available Cellular signaling processes can exhibit pronounced cell-to-cell variability in genetically identical cells. This affects how individual cells respond differentially to the same environmental stimulus. However, the origins of cell-to-cell variability in cellular signaling systems remain poorly understood. Here, we measure the dynamics of phosphorylated MEK and ERK across cell populations and quantify the levels of population heterogeneity over time using high-throughput image cytometry. We use a statistical modeling framework to show that extrinsic noise, particularly that from upstream MEK, is the dominant factor causing cell-to-cell variability in ERK phosphorylation, rather than stochasticity in the phosphorylation/dephosphorylation of ERK. We furthermore show that without extrinsic noise in the core module, variable (including noisy signals would be faithfully reproduced downstream, but the within-module extrinsic variability distorts these signals and leads to a drastic reduction in the mutual information between incoming signal and ERK activity.

Parametric and cycle tests of a 40-AH bipolar nickel-hydrogen battery

Science.gov (United States)

Cataldo, R. L.

1986-01-01

The performance of a 12 V, 40 ampere-hour bipolar battery during various charge current, discharge current, temperature, and pressure operating conditions is investigated. The cell voltages, temperatures, ampere-hours, and watt-hours derived from the charge/discharge cycle tests are studied. Consideration is given to battery voltage and discharge capacity as a function of discharge current, the correlation between energy delivered on a discharge and battery temperature, battery voltage response to pulse discharges, and the voltage-temperature relationship. The data reveal that the bipolar Ni-H battery is applicable to high power systems.

Suprasensory phenomena in those with a bipolar disorder.

Science.gov (United States)

Parker, Gordon; Paterson, Amelia; Romano, Mia; Granville Smith, Isabelle

2018-03-01

To increase awareness of the sensory changes experienced during hypo/manic and depressive states by those with a bipolar disorder and determine if the prevalence of such features is similar across differing bipolar sub-types. We interviewed 66 patients who acknowledged sensory changes during hypo/manic states. They were allocated to bipolar I, bipolar II and soft bipolar diagnostic categories and the prevalence of 10 differing sensory changes was quantified during hypo/manic and depressive phases. Bipolar I patients were just as likely, if not more likely, to report suprasensory changes which typically involved enhancement of senses during hypo/manic phases and muting or blunting during depressive phases. The high prevalence of changes in intuition, empathy, appreciation of danger and predictive capacities suggests that these are more part of the intrinsic bipolar mood domain states and not necessarily suprasensory, while changes in primary senses of smell, taste, vision, touch and hearing appear to more commonly define the suprasensory domain. It is important for clinicians and patients with a bipolar disorder to be aware of non-psychotic, suprasensory phenomena. Identification of such features may aid diagnosis and also explain the recognised increased creativity in those with a bipolar condition.

The bipolarity of light and dark: A review on Bipolar Disorder and circadian cycles.

Science.gov (United States)

Abreu, T; Bragança, M

2015-10-01

Bipolar Disorder is characterized by episodes running the full mood spectrum, from mania to depression. Between mood episodes, residual symptoms remain, as sleep alterations, circadian cycle disturbances, emotional deregulation, cognitive impairment and increased risk for comorbidities. The present review intends to reflect about the most recent and relevant information concerning the biunivocal relation between bipolar disorder and circadian cycles. It was conducted a literature search on PubMed database using the search terms "bipolar", "circadian", "melatonin", "cortisol", "body temperature", "Clock gene", "Bmal1 gene", "Per gene", "Cry gene", "GSK3β", "chronotype", "light therapy", "dark therapy", "sleep deprivation", "lithum" and "agomelatine". Search results were manually reviewed, and pertinent studies were selected for inclusion as appropriate. Several studies support the relationship between bipolar disorder and circadian cycles, discussing alterations in melatonin, body temperature and cortisol rhythms; disruption of sleep/wake cycle; variations of clock genes; and chronotype. Some therapeutics for bipolar disorder directed to the circadian cycles disturbances are also discussed, including lithium carbonate, agomelatine, light therapy, dark therapy, sleep deprivation and interpersonal and social rhythm therapy. This review provides a summary of an extensive research for the relevant literature on this theme, not a patient-wise meta-analysis. In the future, it is essential to achieve a better understanding of the relation between bipolar disorder and the circadian system. It is required to establish new treatment protocols, combining psychotherapy, therapies targeting the circadian rhythms and the latest drugs, in order to reduce the risk of relapse and improve affective behaviour. Copyright © 2015 Elsevier B.V. All rights reserved.

Cell signalling and phospholipid metabolism

Energy Technology Data Exchange (ETDEWEB)

Boss, W.F.

1990-01-01

These studies explored whether phosphoinositide (PI) has a role in plants analogous to its role in animal cells. Although no parallel activity of PI in signal transduction was found in plant cells, activity of inositol phospholipid kinase was found to be modulated by light and by cell wall degrading enzymes. These studies indicate a major role for inositol phospholipids in plant growth and development as membrane effectors but not as a source of second messengers.

Lightweight Stacks of Direct Methanol Fuel Cells

Science.gov (United States)

Narayanan, Sekharipuram; Valdez, Thomas

2004-01-01

An improved design concept for direct methanol fuel cells makes it possible to construct fuel-cell stacks that can weigh as little as one-third as much as do conventional bipolar fuel-cell stacks of equal power. The structural-support components of the improved cells and stacks can be made of relatively inexpensive plastics. Moreover, in comparison with conventional bipolar fuel-cell stacks, the improved fuel-cell stacks can be assembled, disassembled, and diagnosed for malfunctions more easily. These improvements are expected to bring portable direct methanol fuel cells and stacks closer to commercialization. In a conventional bipolar fuel-cell stack, the cells are interspersed with bipolar plates (also called biplates), which are structural components that serve to interconnect the cells and distribute the reactants (methanol and air). The cells and biplates are sandwiched between metal end plates. Usually, the stack is held together under pressure by tie rods that clamp the end plates. The bipolar stack configuration offers the advantage of very low internal electrical resistance. However, when the power output of a stack is only a few watts, the very low internal resistance of a bipolar stack is not absolutely necessary for keeping the internal power loss acceptably low.

Transtorno bipolar

Directory of Open Access Journals (Sweden)

Alda Martin

1999-01-01

Full Text Available Os resultados de estudos de famílias sugerem que o transtorno bipolar tenha uma base genética. Essa hipótese foi reforçada em estudos de adoção e de gêmeos. A herança do transtorno bipolar é complexa, envolve vários genes, além de apresentar heterogeneidade e interação entre fatores genéticos e não-genéticos. Achados, que já foram replicados, já implicaram os cromossomos 4, 12, 18 e 21, entre outros, na busca por genes de suscetibilidade. Os resultados mais promissores foram obtidos através de estudos de ligação. Por outro lado, os estudos de associação geraram dados interessantes, mas ainda vagos. Os estudos de populações de pacientes homogêneos e a melhor definição do fenótipo deverão contribuir para avanços futuros. A identificação dos genes relacionados ao transtorno bipolar irá permitir o melhor entendimento e tratamento dessa doença.

Cell to cell signalling during vertebrate limb bud development

NARCIS (Netherlands)

Panman, Lia

2004-01-01

Communication between cells is essential during embryonic development. The vertebrate limb bud provides us a model to study signalling interactions between cells during patterning of embryonic tissues and organogenesis. In chapter 1 I give an introduction about limb bud development that is focussed

Integrated neurobiology of bipolar disorder

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Vladimir eMaletic

2014-08-01

Full Text Available From a neurobiological perspective there is no such thing as bipolar disorder. Rather, it is almost certainly the case that many somewhat similar, but subtly different, pathological conditions produce a disease state that we currently diagnose as bipolarity. This heterogeneity—reflected in the lack of synergy between our current diagnostic schema and our rapidly advancing scientific understanding of the condition—limits attempts to articulate an integrated perspective on bipolar disorder. However, despite these challenges, scientific findings in recent years are beginning to offer a provisional unified field theory of the disease. This theory sees bipolar disorder as a suite of related neurodevelopmental conditions with interconnected functional abnormalities that often appear early in life and worsen over time. In addition to accelerated loss of volume in brain areas known to be essential for mood regulation and cognitive function, consistent findings have emerged at a cellular level, providing evidence that bipolar disorder is reliably associated with dysregulation of glial-neuronal interactions. Among these glial elements are microglia—the brain’s primary immune elements, which appear to be overactive in the context of bipolarity. Multiple studies now indicate that inflammation is also increased in the periphery of the body in both the depressive and manic phases of the illness, with at least some return to normality in the euthymic state. These findings are consistent with changes in the HPA axis, which are known to drive inflammatory activation. In summary, the very fact that no single gene, pathway or brain abnormality is likely to ever account for the condition is itself an extremely important first step in better articulating an integrated perspective on both its ontological status and pathogenesis. Whether this perspective will translate into the discovery of innumerable more homogeneous forms of bipolarity is one of the great

Diverse phosphorylation patterns of B cell receptor-associated signaling in naïve and memory human B cells revealed by phosphoflow, a powerful technique to study signaling at the single cell level

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Franklin R Toapanta

2012-10-01

Full Text Available Following interaction with cognate antigens, B cells undergo cell activation, proliferation and differentiation. Ligation of the B cell receptor (BCR leads to the phosphorylation of BCR-associated signaling proteins within minutes of antigen binding, a process with profound consequences for the fate of the cells and development of effector immunity. Phosphoflow allows a rapid evaluation of various signaling pathways in complex heterogenous cell subsets. This novel technique was used in combination with multi-chromatic flow cytometry and fluorescent-cell barcoding to study phosphorylation of BCR-associated signaling pathways in naïve and memory human B cell subsets. Proteins of the initiation (Syk, propagation (Btk, Akt and integration (p38MAPK and Erk1/2 signaling units were studied. Switched memory (Sm CD27+ and Sm CD27- phosphorylation patterns were similar when stimulated with anti-IgA or -IgG. In contrast, naïve and unswitched memory (Um cells showed significant differences following IgM stimulation. Enhanced phosphorylation of Syk was observed in Um cells, suggesting a lower activation threshold. This is likely the result of higher amounts of IgM on the cell surface, higher pan-Syk levels and enhanced susceptibility to phosphatase inhibition. All other signaling proteins evaluated also showed some degree of enhanced phosphorylation in Um cells. Furthermore, both the PLC-γ2 and PI3K pathways were activated in Um cells, while only the PI3K pathway was activated on naïve cells. Um cells were the only ones that activated signaling pathways when stimulated with fluorescently-labeled S. Typhi and S. pneumoniae. Finally, simultaneous evaluation of signaling proteins at the single cell level (multi-phosphorylated cells revealed that interaction with gram positive and negative bacteria resulted in complex and diverse signaling patterns. Phosphoflow holds great potential to accelerate vaccine development by identifying signaling profiles in good

Development of a brazing process for the production of water- cooled bipolar plates made of chromium-coated metal foils for PEM fuel cells

International Nuclear Information System (INIS)

Mueller, M; Hoehlich, D; Scharf, I; Lampke, T; Hollaender, U; Maier, H J

2016-01-01

Beside lithium batteries, PEM fuel cells are the most promising strategy as a power source to achieve the targets for introducing and increasing the usage of electric vehicles. Due to limited space and weight problems, water cooled, metallic bipolar plates in a fuel cell metal stack are preferred in motor vehicles. These plates are stamped metal sheets with a complex structure, interconnected media-tight. To meet the multiple tasks and requirements in use, complex and expensive combinations of materials are currently in use (carbon fiber composites, graphite, gold-plated nickel, stainless and acid resistant steel). The production of such plates is expensive as it is connected with considerable effort or the usage of precious metals. As an alternative, metalloid nitrides (CrN, VN, W 2 N, etc.) show a high chemical resistance, hardness and a good conductivity. So this material category meets the basic requirements of a top layer. However, the standard methods for their production (PVD, CVD) are expensive and have a slow deposition rate and a lower layer thicknesses. Because of these limitations, a full functionality over the life cycle of a bipolar plate is not guaranteed. The contribution shows the development and quantification of an alternative production process for bipolar plates. The expectation is to get significant advantages from the combination of chromium electrodeposition and thermochemical treatment to form chromium nitrides. Both processes are well researched and suitable for series production. The thermochemical treatment of the chromium layer also enables a process-integrated brazing. (paper)

Biologically based machine vision: signal analysis of monopolar cells in the visual system of Musca domestica.

Science.gov (United States)

Newton, Jenny; Barrett, Steven F; Wilcox, Michael J; Popp, Stephanie

2002-01-01

Machine vision for navigational purposes is a rapidly growing field. Many abilities such as object recognition and target tracking rely on vision. Autonomous vehicles must be able to navigate in dynamic enviroments and simultaneously locate a target position. Traditional machine vision often fails to react in real time because of large computational requirements whereas the fly achieves complex orientation and navigation with a relatively small and simple brain. Understanding how the fly extracts visual information and how neurons encode and process information could lead us to a new approach for machine vision applications. Photoreceptors in the Musca domestica eye that share the same spatial information converge into a structure called the cartridge. The cartridge consists of the photoreceptor axon terminals and monopolar cells L1, L2, and L4. It is thought that L1 and L2 cells encode edge related information relative to a single cartridge. These cells are thought to be equivalent to vertebrate bipolar cells, producing contrast enhancement and reduction of information sent to L4. Monopolar cell L4 is thought to perform image segmentation on the information input from L1 and L2 and also enhance edge detection. A mesh of interconnected L4's would correlate the output from L1 and L2 cells of adjacent cartridges and provide a parallel network for segmenting an object's edges. The focus of this research is to excite photoreceptors of the common housefly, Musca domestica, with different visual patterns. The electrical response of monopolar cells L1, L2, and L4 will be recorded using intracellular recording techniques. Signal analysis will determine the neurocircuitry to detect and segment images.

Bipolarly stacked electrolyser for energy and space efficient fabrication of supercapacitor electrodes

Science.gov (United States)

Liu, Xiaojuan; Wu, Tao; Dai, Zengxin; Tao, Keran; Shi, Yong; Peng, Chuang; Zhou, Xiaohang; Chen, George Z.

2016-03-01

Stacked electrolysers with titanium bipolar plates are constructed for electrodeposition of polypyrrole electrodes for supercapacitors. The cathode side of the bipolar Ti plates are pre-coated with activated carbon. In this new design, half electrolysis occurs which significantly lowers the deposition voltage. The deposited electrodes are tested in a symmetrical unit cell supercapacitor and an asymmetrical supercapacitor stack. Both devices show excellent energy storage performances and the capacitance values are very close to the design value, suggesting a very high current efficiency during the electrodeposition. The electrolyser stack offers multi-fold benefits for preparation of conducting polymer electrodes, i.e. low energy consumption, facile control of the electrode capacitance and simultaneous preparation of a number of identical electrodes. Therefore, the stacked bipolar electrolyser is a technology advance that offers an engineering solution for mass production of electrodeposited conducting polymer electrodes for supercapacitors.

Unidirectional threshold switching in Ag/Si-based electrochemical metallization cells for high-density bipolar RRAM applications

Science.gov (United States)

Wang, Chao; Song, Bing; Li, Qingjiang; Zeng, Zhongming

2018-03-01

We herein present a novel unidirectional threshold selector for cross-point bipolar RRAM array. The proposed Ag/amorphous Si based threshold selector showed excellent threshold characteristics in positive field, such as high selectivity ( 105), steep slope (type RRAM. By integrating a bipolar RRAM device with the selector, experiments showed that the undesired sneak was significantly suppressed, indicating its potentiality for high-density integrated nonvolatile memory applications.

Enhanced prefrontal function with pharmacotherapy on a response inhibition task in adolescent bipolar disorder.

Science.gov (United States)

Pavuluri, Mani N; Passarotti, Alessandra M; Harral, Erin M; Sweeney, John A

2010-11-01

The aim of the current study is to determine whether pharmacotherapy normalizes cognitive circuitry function supporting voluntary behavioral inhibition in adolescent bipolar disorder. Healthy controls and unmedicated patients with DSM-IV adolescent bipolar disorder in manic, mixed, or hypomanic episodes were matched on demographics and IQ (n = 13 per group; mean age = 14.4 ± 2.4 years). Functional magnetic resonance imaging studies were performed at baseline and after 14 weeks, during which time patients with adolescent bipolar disorder were treated initially with second-generation antipsychotics (SGAs) followed by lamotrigine monotherapy. The primary outcome measure was a Response Inhibition Task, which involved a planned motor response, already "on the way" to execution, that had to be voluntarily inhibited by the subjects in the trials in which a stop signal was presented. There were 6 blocks, each with a predominant rate of either "go" or "stop" trials. The study was conducted from June 2006 through July 2009. All patients showed significant improvement (P adolescent bipolar disorder group than in healthy controls. Increased ventrolateral prefrontal cortex function was related to clinical treatment response. Treatment with SGAs followed by lamotrigine monotherapy enhanced prefrontal and temporal lobe activity during a Response Inhibition Task demonstrating the reversal of disorder-relevant neural circuitry dysfunction in patients with adolescent bipolar disorder. Patient performance was not slowed down with this treatment regimen. clinicaltrials.gov Identifier: NCT00176228. © Copyright 2010 Physicians Postgraduate Press, Inc.

Cell membrane disruption stimulates cAMP and Ca2+ signaling to potentiate cell membrane resealing in neighboring cells

Directory of Open Access Journals (Sweden)

Tatsuru Togo

2017-12-01

Full Text Available Disruption of cellular plasma membranes is a common event in many animal tissues, and the membranes are usually rapidly resealed. Moreover, repeated membrane disruptions within a single cell reseal faster than the initial wound in a protein kinase A (PKA- and protein kinase C (PKC-dependent manner. In addition to wounded cells, recent studies have demonstrated that wounding of Madin-Darby canine kidney (MDCK cells potentiates membrane resealing in neighboring cells in the short-term by purinergic signaling, and in the long-term by nitric oxide/protein kinase G signaling. In the present study, real-time imaging showed that cell membrane disruption stimulated cAMP synthesis and Ca2+ mobilization from intracellular stores by purinergic signaling in neighboring MDCK cells. Furthermore, inhibition of PKA and PKC suppressed the ATP-mediated short-term potentiation of membrane resealing in neighboring cells. These results suggest that cell membrane disruption stimulates PKA and PKC via purinergic signaling to potentiate cell membrane resealing in neighboring MDCK cells.

NK cell activation: distinct stimulatory pathways counterbalancing inhibitory signals.

Science.gov (United States)

Bakker, A B; Wu, J; Phillips, J H; Lanier, L L

2000-01-01

A delicate balance between positive and negative signals regulates NK cell effector function. Activation of NK cells may be initiated by the triggering of multiple adhesion or costimulatory molecules, and can be counterbalanced by inhibitory signals induced by receptors for MHC class I. A common pathway of inhibitory signaling is provided by immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in the cytoplasmic domains of these receptors which mediate the recruitment of SH2 domain-bearing tyrosine phosphate-1 (SHP-1). In contrast to the extensive progress that has been made regarding the negative regulation of NK cell function, our knowledge of the signals that activate NK cells is still poor. Recent studies of the activating receptor complexes have shed new light on the induction of NK cell effector function. Several NK receptors using novel adaptors with immunoreceptor tyrosine-based activation motifs (ITAMs) and with PI 3-kinase recruiting motifs have been implicated in NK cell stimulation.

LEO life tests on a 75 Ah bipolar nickel-hydrogen battery

Science.gov (United States)

Lenhart, S.; Koehler, C.; Applewhite, A.

1988-01-01

The design, building, and testing of an actively cooled 10-cell 75-Ah bipolar nickel/hydrogen battery are discussed. During the last 1000 cycles, the battery has shown some evidence of elecrical performance degradation. In particular, EOC and EOD voltages have increased and decreased by several millivolts, respectively, and deep discharge capacities to a 1.0 V/cell average cutoff voltage have decreased.

Suicide in bipolar disorder: a review.

Science.gov (United States)

Latalova, Klara; Kamaradova, Dana; Prasko, Jan

2014-06-01

Suicide is a leading cause of death in patients with bipolar disorder. Risk factors and prevention of suicide in this illness are the focus of considerable current research. MEDLINE data base was searched for the key words "bipolar disorder" with "suicide", "lithium" with "suicide", "anticonvulsants" with "bipolar disorder", and "anticonvulsants" with "bipolar disorder" and with "suicide". No language or time constraints were applied. The lists of references were searched manually to find additional articles. It is estimated that 25% to 50% of patients with bipolar disorder will attempt suicide at least once over their lifetime, and that 8% to 19% will complete suicide. Mortality rates from cardiovascular diseases are elevated in bipolar disorder. Risk factors for suicide include younger age of onset of the illness, history of past suicidal behavior, family history of suicide acts, comorbid borderline personality disorder and substance use disorders, and hopelessness. The warning signs calling for immediate action include the patients threatening to harm themselves, or looking for ways to kill themselves (seeking access to pills or weapons), or the patient talking or writing about death. Robust evidence supports the effects of lithium treatment in reducing suicidal attempts and completions in bipolar disorder. The evidence for antisuicidal effects of anticonvulsants is weaker. Nevertheless, valproate and other anticonvulsants are frequently prescribed as mood stabilizers. There have been controversial suggestions that this treatment may elevate the risk of suicide, but the data supporting this are not convincing. Psychoeducation can reduce the number of suicide attempts and completions. Suicide in bipolar disorder is a major public health problem. Recent research has expanded our knowledge of risk factors and warning signs. Nevertheless, it appears that the introduction of lithium treatment in the 1970s was the most recent important breakthrough in the prevention

Retinoic acid signalling in thymocytes regulates T cell development

DEFF Research Database (Denmark)

Wendland, Kerstin; Sitnik, Katarzyna Maria; Kotarsky, Knut

in the regulatory regions of targetgenes. RA has been reported to play a direct role in regulating multiple aspects of peripheralT cell responses1, but whether endogenous RA signalling occurs in developingthymocytes and the potential impact of such signals in regulating T cell developmentremains unclear. To address......RARα. This blocks RA signalling in developing thymocytes from the DN3/4 stageonwards and thus allows us to study the role of RA in T cell development...

CD70 reverse signaling enhances NK cell function and immunosurveillance in CD27-expressing B-cell malignancies.

Science.gov (United States)

Al Sayed, Mohamad F; Ruckstuhl, Carla A; Hilmenyuk, Tamara; Claus, Christina; Bourquin, Jean-Pierre; Bornhauser, Beat C; Radpour, Ramin; Riether, Carsten; Ochsenbein, Adrian F

2017-07-20

The interaction of the tumor necrosis factor receptor (TNFR) CD27 with its ligand CD70 is an emerging target to treat cancer. CD27 signaling provides costimulatory signals to cytotoxic T cells but also increases the frequency of regulatory T cells. Similar to other TNFR ligands, CD70 has been shown to initiate intracellular signaling pathways (CD70 reverse signaling). CD27 is expressed on a majority of B-cell non-Hodgkin lymphoma, but its role in the immune control of lymphoma and leukemia is unknown. We therefore generated a cytoplasmic deletion mutant of CD27 (CD27-trunc) to study the role of CD70 reverse signaling in the immunosurveillance of B-cell malignancies in vivo. Expression of CD27-trunc on malignant cells increased the number of tumor-infiltrating interferon γ-producing natural killer (NK) cells. In contrast, the antitumoral T-cell response remained largely unchanged. CD70 reverse signaling in NK cells was mediated via the AKT signaling pathway and increased NK cell survival and effector function. The improved immune control by activated NK cells prolonged survival of CD27-trunc-expressing lymphoma-bearing mice. Finally, CD70 reverse signaling enhanced survival and effector function of human NK cells in a B-cell acute lymphoblastic leukemia xenotransplants model. Therefore, CD70 reverse signaling in NK cells contributes to the immune control of CD27-expressing B-cell lymphoma and leukemia. © 2017 by The American Society of Hematology.

The effect of activation rate on left atrial bipolar voltage in patients with paroxysmal atrial fibrillation.

Science.gov (United States)

Williams, Steven E; Linton, Nick; O'Neill, Louisa; Harrison, James; Whitaker, John; Mukherjee, Rahul; Rinaldi, Christopher A; Gill, Jaswinder; Niederer, Steven; Wright, Matthew; O'Neill, Mark

2017-09-01

Bipolar voltage is used during electroanatomic mapping to define abnormal myocardium, but the effect of activation rate on bipolar voltage is not known. We hypothesized that bipolar voltage may change in response to activation rate. By examining corresponding unipolar signals we sought to determine the mechanisms of such changes. LA extrastimulus mapping was performed during CS pacing in 10 patients undergoing first time paroxysmal atrial fibrillation ablation. Bipolar and unipolar electrograms were recorded using a PentaRay catheter (4-4-4 spacing) and indifferent IVC electrode, respectively. An S1S2 pacing protocol was delivered with extrastimulus coupling interval reducing from 350 to 200 milliseconds. At each recording site (119 ± 37 per LA), bipolar peak-to-peak voltage, unipolar peak to peak voltage and activation delay between unipole pairs was measured. Four patterns of bipolar voltage/extrastimulus coupling interval curves were seen: voltage attenuation with plateau voltage >1 mV (48 ± 15%) or voltage unaffected by coupling interval with plateau voltage >1 mV (17 ± 10%) or voltage attenuation were associated with significantly greater unipolar voltage attenuation at low (25 ± 28 mV/s vs. 9 ± 11 mV/s) and high (23 ± 29 mV/s vs. 6 ± 12 mV/s) plateau voltage sites (P voltage attenuation (P = 0.026). Bipolar electrogram voltage is dependent on activation rate at a significant proportion of sites. Changes in unipolar voltage and timing underlie these effects. These observations have important implications for use of voltage mapping to delineate abnormal atrial substrate. © 2017 The Authors. Journal of Cardiovascular Electrophysiology published by Wiley Periodicals, Inc.

Impairment in emotion perception from body movements in individuals with bipolar I and bipolar II disorder is associated with functional capacity.

Science.gov (United States)

Vaskinn, Anja; Lagerberg, Trine Vik; Bjella, Thomas D; Simonsen, Carmen; Andreassen, Ole A; Ueland, Torill; Sundet, Kjetil

2017-12-01

Individuals with bipolar disorder present with moderate impairments in social cognition during the euthymic state. The impairment extends to theory of mind and to the perception of emotion in faces and voices, but it is unclear if emotion perception from body movements is affected. The main aim of this study was to examine if participants with bipolar disorder perform worse than healthy control participants on a task using point-light displays of human full figures moving in a manner indicative of a basic emotion (angry, happy, sad, fearful, neutral/no emotion). A secondary research question was whether diagnostic subtypes (bipolar I, bipolar II) and history of psychosis impacted on this type of emotion perception. Finally, symptomatic, neurocognitive, and functional correlates of emotion perception from body movements were investigated. Fifty-three individuals with bipolar I (n = 29) or bipolar II (n = 24) disorder, and 84 healthy control participants were assessed for emotion perception from body movements. The bipolar group also underwent clinical, cognitive, and functional assessment. Research questions were analyzed using analyses of variance and bivariate correlations. The bipolar disorder group differed significantly from healthy control participants for emotion perception from body movements (Cohen's d = 0.40). Analyses of variance yielded no effects of sex, diagnostic subtype (bipolar I, bipolar II), or history of psychosis. There was an effect of emotion, indicating that some emotions are easier to recognize. The lack of a significant group × emotion interaction effect points, however, to this being so regardless of the presence of bipolar disorder. Performance was unrelated to manic and depressive symptom load but showed significant associations with neurocognition and functional capacity. Individuals with bipolar disorder had a small but significant impairment in the ability to perceive emotions from body movement. The impairment was global, i

A Comparative Genomic Study in Schizophrenic and in Bipolar Disorder Patients, Based on Microarray Expression Profiling Meta-Analysis

Directory of Open Access Journals (Sweden)

Marianthi Logotheti

2013-01-01

Full Text Available Schizophrenia affecting almost 1% and bipolar disorder affecting almost 3%–5% of the global population constitute two severe mental disorders. The catecholaminergic and the serotonergic pathways have been proved to play an important role in the development of schizophrenia, bipolar disorder, and other related psychiatric disorders. The aim of the study was to perform and interpret the results of a comparative genomic profiling study in schizophrenic patients as well as in healthy controls and in patients with bipolar disorder and try to relate and integrate our results with an aberrant amino acid transport through cell membranes. In particular we have focused on genes and mechanisms involved in amino acid transport through cell membranes from whole genome expression profiling data. We performed bioinformatic analysis on raw data derived from four different published studies. In two studies postmortem samples from prefrontal cortices, derived from patients with bipolar disorder, schizophrenia, and control subjects, have been used. In another study we used samples from postmortem orbitofrontal cortex of bipolar subjects while the final study was performed based on raw data from a gene expression profiling dataset in the postmortem superior temporal cortex of schizophrenics. The data were downloaded from NCBI's GEO datasets.

The relationship between borderline personality disorder and bipolar disorder

Science.gov (United States)

Zimmerman, Mark; Morgan, Theresa A.

2013-01-01

It is clinically important to recognize both bipolar disorder and borderline personality disorder (BPD) in patients seeking treatment for depression, and it is important to distinguish between the two. Research considering whether BPD should be considered part of a bipolar spectrum reaches differing conclusions. We reviewed the most studied question on the relationship between BPD and bipolar disorder: their diagnostic concordance. Across studies, approximately 10% of patients with BPD had bipolar I disorder and another 10% had bipolar II disorder. Likewise, approximately 20% of bipolar II patients were diagnosed with BPD, though only 10% of bipolar I patients were diagnosed with BPD. While the comorbidity rates are substantial, each disorder is nontheless diagnosed in the absence of the other in the vast majority of cases (80% to 90%). In studies examining personality disorders broadly, other personality disorders were more commonly diagnosed in bipolar patients than was BPD. Likewise, the converse is also true: other axis I disorders such as major depression, substance abuse, and post-traumatic stress disorder are also more commonly diagnosed in patients with BPD than is bipolar disorder. These findings challenge the notion that BPD is part of the bipolar spectrum. PMID:24174890

Primary Cilia, Signaling Networks and Cell Migration

DEFF Research Database (Denmark)

Veland, Iben Rønn

Primary cilia are microtubule-based, sensory organelles that emerge from the centrosomal mother centriole to project from the surface of most quiescent cells in the human body. Ciliary entry is a tightly controlled process, involving diffusion barriers and gating complexes that maintain a unique...... this controls directional cell migration as a physiological response. The ciliary pocket is a membrane invagination with elevated activity of clathrin-dependent endocytosis (CDE). In paper I, we show that the primary cilium regulates TGF-β signaling and the ciliary pocket is a compartment for CDE...... on formation of the primary cilium and CDE at the pocket region. The ciliary protein Inversin functions as a molecular switch between canonical and non-canonical Wnt signaling. In paper II, we show that Inversin and the primary cilium control Wnt signaling and are required for polarization and cell migration...

The clinical trajectory of emerging bipolar disorder among the high-risk offspring of bipolar parents: current understanding and future considerations.

Science.gov (United States)

Duffy, A; Vandeleur, C; Heffer, N; Preisig, M

2017-11-22

Relatively little is known about the onset of bipolar disorder, yet the early illness course is already associated with significant morbidity and mortality. Therefore, characterizing the bipolar illness trajectory is key to risk prediction and early intervention advancement. In this narrative review, we discuss key findings from prospective longitudinal studies of the high-risk offspring of bipolar parents and related meta-analyses that inform us about the clinical trajectory of emerging bipolar disorder. Challenges such as phenotypic and etiologic heterogeneity and the non-specificity of early symptoms and syndromes are highlighted. Implications of the findings for both research and clinical practice are discussed. Bipolar disorder in young people at familial risk does not typically onset with a hypomanic or manic episode. Rather the first activated episode is often preceded by years of impairing psychopathological states that vary over development and across emerging bipolar subtype. Taking heterogeneity into account and adopting a more comprehensive approach to diagnosis seems necessary to advance earlier identification and our understanding of the onset of bipolar disorder.

Methodological recommendations for cognition trials in bipolar disorder by the International Society for Bipolar Disorders Targeting Cognition Task Force

DEFF Research Database (Denmark)

Miskowiak, K W; Burdick, K E; Martinez-Aran, A

2017-01-01

OBJECTIVES: To aid the development of treatment for cognitive impairment in bipolar disorder, the International Society for Bipolar Disorders (ISBD) convened a task force to create a consensus-based guidance paper for the methodology and design of cognition trials in bipolar disorder. METHODS...... of treatments to illness stage and using a multimodal approach. CONCLUSIONS: This ISBD task force guidance paper provides the first consensus-based recommendations for cognition trials in bipolar disorder. Adherence to these recommendations will likely improve the sensitivity in detecting treatment efficacy...

Highly conductive thermoplastic composite blends suitable for injection molding of bipolar plates

International Nuclear Information System (INIS)

Mighri, F.; Huneault, M.A.; Champagne, M.F.

2003-01-01

This study aimed at developing highly conductive, lightweight, and low-cost bipolar plates for use in proton exchange membranes (PEM) fuel cells. Injection and compression molding of highly filled polypropylene, PP, and polyphenylene sulfide, PPS, based blends were used as a mean for mass production of bipolar plates. Loadings up to 60-wt% in the form of graphite, conductive carbon black and carbon fibers were investigated. The developed formulations have a combination of properties and processability suitable for bipolar plate manufacturing, such as good chemical resistance, sufficient fluidity, and good electrical and thermal conductivity. Electrical resistivities around 0.15 and 0.09 Ohm-cm were respectively achieved for the PP and PPS-based blends, respectively. Two bipolar plate designs were successfully fabricated by molding the gas flow channels over aluminum plates to form a metallic/polymer composite plate, or simply by direct injection molding of the conductive polymer composite. For the first design, overall plate resistivities of 0.2 and 0.1 Ohm-cm were respectively attained using PP and PPS based blends as conductive skin. A lower volume resistivity of around 0.06 Ohm-cm was attained for the second injected plate design with PPS based blend. (author)

TGF-β Signaling Regulates Pancreatic β-Cell Proliferation through Control of Cell Cycle Regulator p27 Expression

International Nuclear Information System (INIS)

Suzuki, Tomoyuki; Dai, Ping; Hatakeyama, Tomoya; Harada, Yoshinori; Tanaka, Hideo; Yoshimura, Norio; Takamatsu, Tetsuro

2013-01-01

Proliferation of pancreatic β-cells is an important mechanism underlying β-cell mass adaptation to metabolic demands. Increasing β-cell mass by regeneration may ameliorate or correct both type 1 and type 2 diabetes, which both result from inadequate production of insulin by β-cells of the pancreatic islet. Transforming growth factor β (TGF-β) signaling is essential for fetal development and growth of pancreatic islets. In this study, we exposed HIT-T15, a clonal pancreatic β-cell line, to TGF-β signaling. We found that inhibition of TGF-β signaling promotes proliferation of the cells significantly, while TGF-β signaling stimulation inhibits proliferation of the cells remarkably. We confirmed that this proliferative regulation by TGF-β signaling is due to the changed expression of the cell cycle regulator p27. Furthermore, we demonstrated that there is no observed effect on transcriptional activity of p27 by TGF-β signaling. Our data show that TGF-β signaling mediates the cell-cycle progression of pancreatic β-cells by regulating the nuclear localization of CDK inhibitor, p27. Inhibition of TGF-β signaling reduces the nuclear accumulation of p27, and as a result this inhibition promotes proliferation of β-cells

VALPROATE, BIPOLAR DISORDER AND POLYCYSTIC OVARIAN SYNDROME.

Science.gov (United States)

Okanović, Milana; Zivanović, Olga

2016-01-01

Polycystic ovarian syndrome is a syndrome of ovarian dysfunction with the principal features of hyperandrogenism and polycystic ovary morphology. A large number of studies conducted on this topic have suggested a possible role of anticonvulsants, particularly valproate, in the pathogenesis or risk factors associated with polycystic ovarian syndrome. Bipolar treatment guidelines from Canada and the United States of America recommend valproate as the first line strategy in the acute treatment of bipolar disorder. Most persons with bipolar disorder require maintenance treatment. Long-term administration of valproate in women with bipolar disorder or epilepsy is believed to result in the increased risk of hyperandrogenism, menstrual abnormalities and polycystic ovaries. Valproate may also increase the risk of infertility and other associated symptoms of polycystic ovarian syndrome. Therefore, particular caution is indicated in the use of valproate in women of reproductive age. The treatment of the female patients with bipolar disorder presents various challenges for the clinician. Every woman of reproductive age needs to know the risk and benefits of her pharmacologic treatment options. Bipolar disorder should be considered chronic disorder, whose development is largely affected by hormonal changes and reproductive cycle in women. These issues should be researched more thoroughly in order to opt for the most appropriate treatment in women with bipolar disorder.

Distinctions of bipolar disorder symptoms in adolescence.

Science.gov (United States)

Gudiene, Devika; Leskauskas, Darius; Markeviciūte, Aurelija; Klimavicius, Dalius; Adomaitiene, Virginija

2008-01-01

Bipolar disorder in adolescents is a serious mental illness with problematic diagnosis that adversely affects social, academic, emotional, and family functioning. The objective of this study was to analyze features of premorbid and clinical symptoms, comorbidity, and course of bipolar disorder in adolescence. Data for analysis were collected from all case histories (N=6) of 14-18-year-old patients, hospitalized with diagnosis of bipolar disorder in the Unit of Children's and Adolescents' Psychiatry, Department of Psychiatry, Hospital of Kaunas University of Medicine, during the period from 2000 to 2005. Analysis of bipolar disorder course showed that five patients previously had been diagnosed with an episode of depression. The most frequent symptoms typical to bipolar disorder were disobedience and impulsive behavior, rapid changes of mood. The most common premorbid features were frequent changes of mood, being active in communication, hyperactive behavior. Adolescence-onset bipolar disorder was frequently comorbid with emotionally instable personality disorder, borderline type. Findings of the study confirm the notion that oppositional or impulsive behavior, rapid changes of mood without any reason, dysphoric mood and euphoric mood episodes with increased energy were cardinal symptoms of bipolar disorder with mania in adolescents. Most frequent premorbid features of these patients were quite similar to attention-deficit/hyperactivity disorder making differential diagnosis problematic.

Electric field with bipolar structure during magnetic reconnection without a guide field

Science.gov (United States)

Guo, Jun

2014-05-01

We present a study on the polarized electric field during the collisionless magnetic reconnection of antiparallel fields using two dimensional particle-in-cell simulations. The simulations demonstrate clearly that electron holes and electric field with bipolar structure are produced during magnetic reconnection without a guide field. The electric field with bipolar structure can be found near the X-line and on the separatrix and the plasma sheet boundary layer, which is consistent with the observations. These structures will elongate electron's time staying in the diffusion region. In addition, the electric fields with tripolar structures are also found in our simulation.

Life cycle test results of a bipolar nickel hydrogen battery

Science.gov (United States)

Cataldo, R. L.

1985-01-01

A history is given of low Earth orbit (LEO) laboratory test data on a 6.5 ampere-hour bipolar nickel hydrogen battery designed and built at the NASA Lewis Research Center. The bipolar concept is a means of achieving the goal of producing an acceptable battery, of higher energy density, able to withstand the demands of low-Earth-orbit regimes. Over 4100 LEO cycles were established on a ten cell battery. It seems that any perturbation on normal cycling effects the cells performance. Explanations and theories of the battery's behavior are varied and widespread among those closely associated with it. Deep discharging does provide a reconditioning effect and further experimentation is planned in this area. The battery watt-hour efficiency is about 75 percent and the time averaged, discharge voltage is about 1.26 volts for all cells at both the C/4 and LEO rate. Since a significant portion of the electrode capacity has degraded, the LEO cycle discharges are approaching depths of 90 to 100 percent of the high rate capacity. Therefore, the low end-of-discharge voltages occur precipitously after the knee of the discharge curve and is more an indication of electrode capacity and is a lesser indicator of overall cell performance.

Vitamin D controls T cell antigen receptor signaling and activation of human T cells

DEFF Research Database (Denmark)

von Essen, Marina Rode; Kongsbak-Wismann, Martin; Schjerling, Peter

2010-01-01

Phospholipase C (PLC) isozymes are key signaling proteins downstream of many extracellular stimuli. Here we show that naive human T cells had very low expression of PLC-gamma1 and that this correlated with low T cell antigen receptor (TCR) responsiveness in naive T cells. However, TCR triggering...... led to an upregulation of approximately 75-fold in PLC-gamma1 expression, which correlated with greater TCR responsiveness. Induction of PLC-gamma1 was dependent on vitamin D and expression of the vitamin D receptor (VDR). Naive T cells did not express VDR, but VDR expression was induced by TCR...... signaling via the alternative mitogen-activated protein kinase p38 pathway. Thus, initial TCR signaling via p38 leads to successive induction of VDR and PLC-gamma1, which are required for subsequent classical TCR signaling and T cell activation....

Integrated Neurobiology of Bipolar Disorder

Science.gov (United States)

Maletic, Vladimir; Raison, Charles

2014-01-01

From a neurobiological perspective there is no such thing as bipolar disorder. Rather, it is almost certainly the case that many somewhat similar, but subtly different, pathological conditions produce a disease state that we currently diagnose as bipolarity. This heterogeneity – reflected in the lack of synergy between our current diagnostic schema and our rapidly advancing scientific understanding of the condition – limits attempts to articulate an integrated perspective on bipolar disorder. However, despite these challenges, scientific findings in recent years are beginning to offer a provisional “unified field theory” of the disease. This theory sees bipolar disorder as a suite of related neurodevelopmental conditions with interconnected functional abnormalities that often appear early in life and worsen over time. In addition to accelerated loss of volume in brain areas known to be essential for mood regulation and cognitive function, consistent findings have emerged at a cellular level, providing evidence that bipolar disorder is reliably associated with dysregulation of glial–neuronal interactions. Among these glial elements are microglia – the brain’s primary immune elements, which appear to be overactive in the context of bipolarity. Multiple studies now indicate that inflammation is also increased in the periphery of the body in both the depressive and manic phases of the illness, with at least some return to normality in the euthymic state. These findings are consistent with changes in the hypothalamic–pituitary–adrenal axis, which are known to drive inflammatory activation. In summary, the very fact that no single gene, pathway, or brain abnormality is likely to ever account for the condition is itself an extremely important first step in better articulating an integrated perspective on both its ontological status and pathogenesis. Whether this perspective will translate into the discovery of innumerable more homogeneous forms of

Genética do transtorno bipolar Genetics of bipolar disorder

Directory of Open Access Journals (Sweden)

Leandro Michelon

2004-10-01

Full Text Available O Transtorno bipolar (TB possui alta prevalência na população mundial e causa perdas significativas na vida dos portadores. É uma doença cuja herança genética se caracteriza por mecanismos complexos de transmissão envolvendo múltiplos genes. Na tentativa de identificar genes de vulnerabilidade para o TB, várias estratégias de investigação genética têm sido utilizadas. Estudos de ligação apontam diversas regiões cromossômicas potencialmente associadas ao TB, cujos marcadores ou genes podem ser candidatos para os estudos de associação. Genes associados aos sistemas monoaminérgicos e vias de sinalização intracelulares são candidatos para investigação da etiologia genética do TB. Novas técnicas de mapeamento de expressão gênica em tecidos especializados apontam para novos genes cujas mutações possam ser responsáveis pelo aparecimento da doença. Em virtude da complexidade do modo de transmissão do TB e de sua heterogeneidade fenotípica, muitas dificuldades são encontradas na determinação desses genes de vulnerabilidade. Até o momento, há apenas resultados preliminares identificando alguns genes associados à vulnerabilidade para desenvolver o TB. Entretanto, a compreensão crescente dos mecanismos epigenéticos de controle da expressão gênica e a abordagem dimensional dos transtornos mentais podem colaborar nas investigações futuras em genética psiquiátrica.Bipolar disorder (BD is a worldwide highly prevalent mental disease. This disorder has a genetic inheritance characterized by complex transmission mechanisms involving multiple genes. Many investigation strategies have been put forward in order to identify BD susceptibility genes. Linkage studies reveal markers and candidate genes for the association studies. Monoaminergic system genes and intracellular signaling pathway genes are also important candidates to be investigated in the etiology of this disorder. Recent techniques of gene expression

Calcium specificity signaling mechanisms in abscisic acid signal transduction in Arabidopsis guard cells

Science.gov (United States)

Brandt, Benjamin; Munemasa, Shintaro; Wang, Cun; Nguyen, Desiree; Yong, Taiming; Yang, Paul G; Poretsky, Elly; Belknap, Thomas F; Waadt, Rainer; Alemán, Fernando; Schroeder, Julian I

2015-01-01

A central question is how specificity in cellular responses to the eukaryotic second messenger Ca2+ is achieved. Plant guard cells, that form stomatal pores for gas exchange, provide a powerful system for in depth investigation of Ca2+-signaling specificity in plants. In intact guard cells, abscisic acid (ABA) enhances (primes) the Ca2+-sensitivity of downstream signaling events that result in activation of S-type anion channels during stomatal closure, providing a specificity mechanism in Ca2+-signaling. However, the underlying genetic and biochemical mechanisms remain unknown. Here we show impairment of ABA signal transduction in stomata of calcium-dependent protein kinase quadruple mutant plants. Interestingly, protein phosphatase 2Cs prevent non-specific Ca2+-signaling. Moreover, we demonstrate an unexpected interdependence of the Ca2+-dependent and Ca2+-independent ABA-signaling branches and the in planta requirement of simultaneous phosphorylation at two key phosphorylation sites in SLAC1. We identify novel mechanisms ensuring specificity and robustness within stomatal Ca2+-signaling on a cellular, genetic, and biochemical level. DOI: http://dx.doi.org/10.7554/eLife.03599.001 PMID:26192964

Prolonged sulforaphane treatment activates survival signaling in nontumorigenic NCM460 colon cells but apoptotic signaling in tumorigenic HCT116 colon cells.

Science.gov (United States)

Zeng, Huawei; Trujillo, Olivia N; Moyer, Mary P; Botnen, James H

2011-01-01

Sulforaphane (SFN) is a naturally occurring chemopreventive agent; the induction of cell cycle arrest and apoptosis is a key mechanism by which SFN exerts its colon cancer prevention. However, little is known about the differential effects of SFN on colon cancer and normal cells. In this study, we demonstrated that SFN (15 μmol/L) exposure (72 h) inhibited cell proliferation by up to 95% in colon cancer cells (HCT116) and by 52% in normal colon mucosa-derived (NCM460) cells. Our data also showed that SFN exposure (5 and 10 μmol/L) led to the reduction of G1 phase cell distribution and an induction of apoptosis in HCT116 cells, but to a much lesser extent in NCM460 cells. Furthermore, the examination of mitogen-activated protein kinase (MAPK) signaling status revealed that SFN upregulated the phosphorylation of extracellular-regulated kinase 1/2 (ERK1/2) in NCM460 cells but not in HCT116 cells. In contrast, SFN enhanced the phosphorylation of stress-activated protein kinase (SAPK) and decreased cellular myelocytomatosis oncogene (c-Myc) expression in HCT116 cells but not NCM460 cells. Taken together, the activation of survival signaling in NCM460 cells and apoptotic signaling in HCT116 cells may play a critical role in SFN's stronger potential of inhibiting cell proliferation in colon cancer cells than in normal colon cells. Copyright © 2011, Taylor & Francis Group, LLC

Comorbid medical illness in bipolar disorder.

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Forty, Liz; Ulanova, Anna; Jones, Lisa; Jones, Ian; Gordon-Smith, Katherine; Fraser, Christine; Farmer, Anne; McGuffin, Peter; Lewis, Cathryn M; Hosang, Georgina M; Rivera, Margarita; Craddock, Nick

2014-12-01

Individuals with a mental health disorder appear to be at increased risk of medical illness. To examine rates of medical illnesses in patients with bipolar disorder (n = 1720) and to examine the clinical course of the bipolar illness according to lifetime medical illness burden. Participants recruited within the UK were asked about the lifetime occurrence of 20 medical illnesses, interviewed using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) and diagnosed according to DSM-IV criteria. We found significantly increased rates of several medical illnesses in our bipolar sample. A high medical illness burden was associated with a history of anxiety disorder, rapid cycling mood episodes, suicide attempts and mood episodes with a typically acute onset. Bipolar disorder is associated with high rates of medical illness. This comorbidity needs to be taken into account by services in order to improve outcomes for patients with bipolar disorder and also in research investigating the aetiology of affective disorder where shared biological pathways may play a role. Royal College of Psychiatrists.

Epidemiology, neurobiology and pharmacological interventions related to suicide deaths and suicide attempts in bipolar disorder: Part I of a report of the International Society for Bipolar Disorders Task Force on Suicide in Bipolar Disorder

Science.gov (United States)

Schaffer, Ayal; Isometsä, Erkki T; Tondo, Leonardo; Moreno, Doris H; Sinyor, Mark; Kessing, Lars Vedel; Turecki, Gustavo; Weizman, Abraham; Azorin, Jean-Michel; Ha, Kyooseob; Reis, Catherine; Cassidy, Frederick; Goldstein, Tina; Rihmer, Zoltán; Beautrais, Annette; Chou, Yuan-Hwa; Diazgranados, Nancy; Levitt, Anthony J; Zarate, Carlos A; Yatham, Lakshmi

2016-01-01

Objectives Bipolar disorder is associated with elevated risk of suicide attempts and deaths. Key aims of the International Society for Bipolar Disorders Task Force on Suicide included examining the extant literature on epidemiology, neurobiology and pharmacotherapy related to suicide attempts and deaths in bipolar disorder. Methods Systematic review of studies from 1 January 1980 to 30 May 2014 examining suicide attempts or deaths in bipolar disorder, with a specific focus on the incidence and characterization of suicide attempts and deaths, genetic and non-genetic biological studies and pharmacotherapy studies specific to bipolar disorder. We conducted pooled, weighted analyses of suicide rates. Results The pooled suicide rate in bipolar disorder is 164 per 100,000 person-years (95% confidence interval = [5, 324]). Sex-specific data on suicide rates identified a 1.7:1 ratio in men compared to women. People with bipolar disorder account for 3.4–14% of all suicide deaths, with self-poisoning and hanging being the most common methods. Epidemiological studies report that 23–26% of people with bipolar disorder attempt suicide, with higher rates in clinical samples. There are numerous genetic associations with suicide attempts and deaths in bipolar disorder, but few replication studies. Data on treatment with lithium or anticonvulsants are strongly suggestive for prevention of suicide attempts and deaths, but additional data are required before relative anti-suicide effects can be confirmed. There were limited data on potential anti-suicide effects of treatment with antipsychotics or antidepressants. Conclusion This analysis identified a lower estimated suicide rate in bipolar disorder than what was previously published. Understanding the overall risk of suicide deaths and attempts, and the most common methods, are important building blocks to greater awareness and improved interventions for suicide prevention in bipolar disorder. Replication of genetic findings and

Transcriptomic Analysis of Induced Pluripotent Stem Cells Derived from Patients with Bipolar Disorder from an Old Order Amish Pedigree.

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Kwi Hye Kim

Full Text Available Fibroblasts from patients with Type I bipolar disorder (BPD and their unaffected siblings were obtained from an Old Order Amish pedigree with a high incidence of BPD and reprogrammed to induced pluripotent stem cells (iPSCs. Established iPSCs were subsequently differentiated into neuroprogenitors (NPs and then to neurons. Transcriptomic microarray analysis was conducted on RNA samples from iPSCs, NPs and neurons matured in culture for either 2 weeks (termed early neurons, E or 4 weeks (termed late neurons, L. Global RNA profiling indicated that BPD and control iPSCs differentiated into NPs and neurons at a similar rate, enabling studies of differentially expressed genes in neurons from controls and BPD cases. Significant disease-associated differences in gene expression were observed only in L neurons. Specifically, 328 genes were differentially expressed between BPD and control L neurons including GAD1, glutamate decarboxylase 1 (2.5 fold and SCN4B, the voltage gated type IV sodium channel beta subunit (-14.6 fold. Quantitative RT-PCR confirmed the up-regulation of GAD1 in BPD compared to control L neurons. Gene Ontology, GeneGo and Ingenuity Pathway Analysis of differentially regulated genes in L neurons suggest that alterations in RNA biosynthesis and metabolism, protein trafficking as well as receptor signaling pathways may play an important role in the pathophysiology of BPD.

Bipolar pulse generator for intense pulsed ion beam accelerator

International Nuclear Information System (INIS)

Ito, H.; Igawa, K.; Kitamura, I.; Masugata, K.

2007-01-01

A new type of pulsed ion beam accelerator named ''bipolar pulse accelerator'' (BPA) has been proposed in order to improve the purity of intense pulsed ion beams. To confirm the principle of the BPA, we developed a bipolar pulse generator for the bipolar pulse experiment, which consists of a Marx generator and a pulse forming line (PFL) with a rail gap switch on its end. In this article, we report the first experimental result of the bipolar pulse and evaluate the electrical characteristics of the bipolar pulse generator. When the bipolar pulse generator was operated at 70% of the full charge condition of the PFL, the bipolar pulse with the first (-138 kV, 72 ns) and the second pulse (+130 kV, 70 ns) was successfully obtained. The evaluation of the electrical characteristics indicates that the developed generator can produce the bipolar pulse with fast rise time and sharp reversing time

Bipolar disorder diagnosis: challenges and future directions

Science.gov (United States)

Phillips, Mary L; Kupfer, David J

2018-01-01

Bipolar disorder refers to a group of affective disorders, which together are characterised by depressive and manic or hypomanic episodes. These disorders include: bipolar disorder type I (depressive and manic episodes: this disorder can be diagnosed on the basis of one manic episode); bipolar disorder type II (depressive and hypomanic episodes); cyclothymic disorder (hypomanic and depressive symptoms that do not meet criteria for depressive episodes); and bipolar disorder not otherwise specified (depressive and hypomanic-like symptoms that do not meet the diagnostic criteria for any of the aforementioned disorders). Bipolar disorder type II is especially difficult to diagnose accurately because of the difficulty in differentiation of this disorder from recurrent unipolar depression (recurrent depressive episodes) in depressed patients. The identification of objective biomarkers that represent pathophysiologic processes that differ between bipolar disorder and unipolar depression can both inform bipolar disorder diagnosis and provide biological targets for the development of new and personalised treatments. Neuroimaging studies could help the identification of biomarkers that differentiate bipolar disorder from unipolar depression, but the problem in detection of a clear boundary between these disorders suggests that they might be better represented as a continuum of affective disorders. Innovative combinations of neuroimaging and pattern recognition approaches can identify individual patterns of neural structure and function that accurately ascertain where a patient might lie on a behavioural scale. Ultimately, an integrative approach, with several biological measurements using different scales, could yield patterns of biomarkers (biosignatures) to help identify biological targets for personalised and new treatments for all affective disorders. PMID:23663952

Preparation of bipolar membranes by electrospinning

International Nuclear Information System (INIS)

Pan, Jiefeng; Hou, Linxiao; Wang, Qiuyue; He, Yubin; Wu, Liang; Mondal, Abhishek N.; Xu, Tongwen

2017-01-01

A new preparative pathway for the bipolar membranes was initiated via the electrospinning and hot-press process. The prepared bipolar membrane was consisting of sulfonated poly (phenylene oxide), polyethylene glycol, and quaternized poly (phenylene oxide). The above mentioned membrane was fabricated by the continuous electrospinning of the respective layer, followed by the solvent atmosphere treatment and hot-pressing, to obtain a transparent and dense structure. The thickness of each layer can be easily tuned by controlling the electrospinning parameters. The clear interfacial structure was observed and confirmed by the scanning electron microscope. The bipolar performance is evaluated by the current–voltage curves and production yield of acid and base. The final optimized bipolar membrane had similar yield of acid and base as the casting membrane. However, extremely lower potential drop value was observed when they are applied for the production of acid and base. The experimental results showed that, electrospinning is an effective and well controlled way to fabricate bipolar membranes, in which anion or cation exchange layer as well as interfacial layer can be easily changed or added as requested. - Highlights: • Bipolar membranes were prepared through electrospinning followed by post-treatment. • As-prepared membranes were successfully applied in electrodialysis for production of acid and base. • Electrospun membranes exhibit better performance than the casting ones.

Preparation of bipolar membranes by electrospinning

Energy Technology Data Exchange (ETDEWEB)

Pan, Jiefeng; Hou, Linxiao; Wang, Qiuyue; He, Yubin; Wu, Liang; Mondal, Abhishek N.; Xu, Tongwen, E-mail: twxu@ustc.edu.cn

2017-01-15

A new preparative pathway for the bipolar membranes was initiated via the electrospinning and hot-press process. The prepared bipolar membrane was consisting of sulfonated poly (phenylene oxide), polyethylene glycol, and quaternized poly (phenylene oxide). The above mentioned membrane was fabricated by the continuous electrospinning of the respective layer, followed by the solvent atmosphere treatment and hot-pressing, to obtain a transparent and dense structure. The thickness of each layer can be easily tuned by controlling the electrospinning parameters. The clear interfacial structure was observed and confirmed by the scanning electron microscope. The bipolar performance is evaluated by the current–voltage curves and production yield of acid and base. The final optimized bipolar membrane had similar yield of acid and base as the casting membrane. However, extremely lower potential drop value was observed when they are applied for the production of acid and base. The experimental results showed that, electrospinning is an effective and well controlled way to fabricate bipolar membranes, in which anion or cation exchange layer as well as interfacial layer can be easily changed or added as requested. - Highlights: • Bipolar membranes were prepared through electrospinning followed by post-treatment. • As-prepared membranes were successfully applied in electrodialysis for production of acid and base. • Electrospun membranes exhibit better performance than the casting ones.

Comorbidity bipolar disorder and personality disorders.

Science.gov (United States)

Latalova, Klara; Prasko, Jan; Kamaradova, Dana; Sedlackova, Jana; Ociskova, Marie

2013-01-01

Outcome in bipolar patients can be affected by comorbidity of other psychiatric disorders. Comorbid personality disorders are frequent and may complicate the course of bipolar illness. We have much information about treating patients with uncomplicated bipolar disorder (BD) but much less knowledge about possibilities for patients with the comorbidity of BD and personality disorder. We conducted a series of literature searches using, as key words or as items in indexed fields, bipolar disorder and personality disorder or personality traits. Articles were obtained by searching MEDLINE from 1970 to 2012. In addition, we used other papers cited in articles from these searches, or cited in articles used in our own work. Tests of personality traits indicated that euthymic bipolar patients have higher scores on harm avoidance, reward dependence, and novelty seeking than controls. Elevation of novelty seeking in bipolar patients is associated with substance abuse comorbidity. Comorbidity with personality disorders in BD patients is associated with a more difficult course of illness (such as longer episodes, shorter time euthymic, and earlier age at onset) and an increase in comorbid substance abuse, suicidality and aggression. These problems are particularly pronounced in comorbidity with borderline personality disorder. Comorbidity with antisocial personality disorder elicits a similar spectrum of difficulties; some of the antisocial behavior exhibited by patients with this comorbidity is mediated by increased impulsivity.

Thematic minireview series: cell biology of G protein signaling.

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Dohlman, Henrik G

2015-03-13

This thematic series is on the topic of cell signaling from a cell biology perspective, with a particular focus on G proteins. G protein-coupled receptors (GPCRs, also known as seven-transmembrane receptors) are typically found at the cell surface. Upon agonist binding, these receptors will activate a GTP-binding G protein at the cytoplasmic face of the plasma membrane. Additionally, there is growing evidence that G proteins can also be activated by non-receptor binding partners, and they can signal from non-plasma membrane compartments. The production of second messengers at multiple, spatially distinct locations represents a type of signal encoding that has been largely neglected. The first minireview in the series describes biosensors that are being used to monitor G protein signaling events in live cells. The second describes the implementation of antibody-based biosensors to dissect endosome signaling by G proteins and their receptors. The third describes the function of a non-receptor, cytoplasmic activator of G protein signaling, called GIV (Girdin). Collectively, the advances described in these articles provide a deeper understanding and emerging opportunities for new pharmacology. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Family environment patterns in families with bipolar children.

Science.gov (United States)

Belardinelli, Cecilia; Hatch, John P; Olvera, Rene L; Fonseca, Manoela; Caetano, Sheila C; Nicoletti, Mark; Pliszka, Steven; Soares, Jair C

2008-04-01

We studied the characteristics of family functioning in bipolar children and healthy comparison children. We hypothesized that the family environment of bipolar children would show greater levels of dysfunction as measured by the Family Environment Scale (FES). We compared the family functioning of 36 families that included a child with DSM-IV bipolar disorder versus 29 comparison families that included only healthy children. All subjects and their parents were assessed with the K-SADS-PL interview. The parents completed the FES to assess their current family functioning. Multivariate analysis of variance was used to compare the family environment of families with and without offspring with bipolar disorder. Parents of bipolar children reported lower levels of family cohesion (pfamilies where a parent had a history of mood disorders compared to families where parents had no history of mood disorders. Length of illness in the affected child was inversely associated with family cohesion (r=-0.47, p=0.004). Due to the case-control design of the study, we cannot comment on the development of these family problems or attribute their cause specifically to child bipolar disorder. Families with bipolar children show dysfunctional patterns related to interpersonal interactions and personal growth. A distressed family environment should be addressed when treating children with bipolar disorder.

POWER, METALLURGICAL AND CHEMICAL MECHANICAL ENGINEERING THERMOELECTRIC EVENTS IN LIGHT-EMITTING BIPOLAR SEMICONDUCTOR STRUCTURES

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P. A. Magomedova

2017-01-01

Full Text Available Objective. The development of light-emitting bipolar semiconductor structures having a low level of parasitic heat release.Methods. A method for converting thermoelectric heat in bipolar semiconductor structures into optical radiation to divert the excess energy into the environment was developed. At the same time, the cooling effect on thermoelectric junctions remains. Instead of an inertial process of conductive or convective heat transfer, practically instantaneous heat removal from electronic components to the environment takes place.Results. As a result, light-emitting bipolar semiconductor structures will allow more powerful devices with greater speed and degree of integration to be created. It is possible to produce transparent LED matrices with a two-way arrangement of transparent solar cells and mirror metal electrodes along the perimeter. When current is applied, the LED matrix on one of the transitions will absorb thermal energy; on other electrodes, it will emit radiation that is completely recovered into electricity by means of transparent solar cells following repeated reflection between the mirror electrodes. The low efficiency of solar cells will be completely compensated for with the multiple passages of photons through these batteries.Conclusion. Light-emitting bipolar semiconductor structures will not only improve the reliability of electronic components in a wide range of performance characteristics, but also improve energy efficiency through the use of optical radiation recovery. Semiconductor thermoelectric devices using optical phenomena in conjunction with the Peltier effect allow a wide range of energy-efficient components of radio electronic equipment to be realised, both for discrete electronics and for microsystem techniques. Systems for obtaining ultra-low temperatures in order to achieve superconductivity are of particular value. 

Bipolar Disorder and Obsessive Compulsive Disorder Comorbidity

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Necla Keskin

2014-08-01

Full Text Available The comorbidity of bipolar disorder and anxiety disorders is a well known concept. Obsessive-compulsive disorder is the most commonly seen comorbid anxiety disorder in bipolar patients. Some genetic variants, neurotransmitters especially serotonergic systems and second-messenger systems are thought to be responsible for its etiology. Bipolar disorder alters the clinical aspects of obsessive compulsive disorder and is associated with poorer outcome. The determination of comorbidity between bipolar disorder and obsessive compulsive disorder is quite important for appropriate clinical management and treatment. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2014; 6(4.000: 429-437

An analog front-end bipolar-transistor integrated circuit for the SDC silicon tracker

International Nuclear Information System (INIS)

Kipnis, I.; Spieler, H.; Collins, T.

1994-01-01

Since 1989 the Solenoidal Detector Collaboration (SDC) has been developing a general purpose detector to be operated at the Superconducting Super Collider (SSC). A low-noise, low-power, high-bandwidth, radiation hard, silicon bipolar-transistor full-custom integrated circuit (IC) containing 64 channels of analog signal processing has been developed for the SDS silicon tracker. The IC was designed and tested at LBL and was fabricated using AT and T's CBIC-U2, 4 GHz f T complementary bipolar technology. Each channel contains the following functions: low-noise preamplification, pulse shaping and threshold discrimination. This is the first iteration of the production analog IC for the SDC silicon tracker. The IC is laid out to directly match the 50 μm pitch double-sided silicon strip detector. The chip measures 6.8 mm x 3.1 mm and contains 3,600 transistors. Three stages of amplification provide 180 mV/fC of gain with a 35 nsec peaking time at the comparator input. For a 14 pF detector capacitance, the equivalent noise charge is 1300 el. rms at a power consumption of 1 mW/channel from a single 3.5 V supply. With the discriminator threshold set to 4 times the noise level, a 16nsec time-walk for 1.25 to 10 fC signals is achieved using a time-walk compensation network. Irradiation tests at TRIUMF to a φ = 10 14 protons/cm 2 have been performed on the JC, demonstrating the radiation hardness of the complementary bipolar process

Bipolar (spectrum) disorder and mood stabilization: standing at the crossroads?

OpenAIRE

De Fruyt, Jurgen; Demyttenaere, Koen

2007-01-01

Diagnosis and treatment of bipolar disorder has long been a neglected discipline. Recent years have shown an upsurge in bipolar research. When compared to major depressive disorder, bipolar research still remains limited and more expert based than evidence based. In bipolar diagnosis the focus is shifting from classic mania to bipolar depression and hypomania. There is a search for bipolar signatures in symptoms and course of major depressive episodes. The criteria for hypomania are softened,...

Radioresistance-related signaling pathways in nasopharyngeal carcinoma cells

International Nuclear Information System (INIS)

Guo Ya; Zhu Xiaodong; Qu Song; Su Fang; Wang Qi; Zhang Wei

2011-01-01

Objective: To study the difference of gene expression profile between the radioresistant human nasopharyngeal carcinoma cell line CNE-2R and CNE-2, and to screen the signaling pathway associated with radioresistance of nasopharyngeal carcinoma. Methods: The radioresistant nasopharyngeal carcinoma cell line CNE-2R was constructed from the original cell line CNE-2. CNE-2R and CNE-2 cells were cultured and administered with 60 Co γ-ray irradiation at the dose of 400 cGy for 15 times. Human-6v 3.0 whole genome expression profile was used to screen the differentially expressed genes. Bioinformatic analysis was used to identify the pathways related to radioresistance. Results: The number of the differentially expressed genes that were found in these 2 experiments was 374. The Kegg pathway and Biocarta pathway analysis of the differentially expressed genes showed the biological importance of Toll-like receptor signaling pathway and IL-1 R-mediated signal transduction pathway to the radioresistance of the CNE-2R cells and the significant differences of 13 genes in these 2 pathways,including JUN, MYD88, CCL5, CXCL10, STAT1, LY96, FOS, CCL3, IL-6, IL-8, IL-1α, IL-1β, and IRAK2 (t=13.47-66.57, P<0.05). Conclusions: Toll-like receptor signaling pathway and IL-1R-mediated signal transduction pathway might be related to the occurrence of radioresistance. (authors)

The bipolar II disorder personality traits, a true syndrome?

Science.gov (United States)

Gudmundsson, Einar

2015-06-01

The author was struck by the similarities and commonality of complaints, aside from mood swings, made by Bipolar II patients and started registrating these complaints. This registrational work eventually led to the development of The Bipolar II Syndome Checklist. The aim of this work was to understand how widely the Bipolar II disorder affects the personality, and what disturbing personality traits are the most common? Deliberately, no attempt was made to diagnose psychiatric comorbidities, in the hope that one would get a clearer view of what symptoms, if any, could be considered a natural part of the Bipolar II Disorder. As far as the author knows this is a novel approach. 105 Bipolar II patients completed the Bipolar II Syndrome Checklist. The answers to the 44 questions on the list are presented in tables. Symptoms like anxiety, low self esteem, paranoia, extreme hurtfulness, migraine, Post Partum Depression, obsessive traits, alcoholism in the family are amongst the findings which will be presented in greater detail. No control group. Bipolar I patients excluded. The Bipolar II Syndrome Checklist has not been systematically validated. The results show that Bipolar II Disorder causes multiple symptoms so commonly that it may be justified to describe it as a syndrome, The Bipolar II Syndrome. Also these disturbances commonly lie in families of Bipolar II patients and are in all likelihood, greatly underdiagnosed. The clinical relevance of this study lies in increasing our knowledge and understanding of the nature of the Bipolar II Disorder, which in all probability will increase the diagnostic and treatment accuracy, since clinicians are more likely to scan for other symptoms needing treatment. Copyright © 2015 Elsevier B.V. All rights reserved.

Differential diagnosis of bipolar disorder and major depressive disorder.

Science.gov (United States)

Hirschfeld, R M

2014-12-01

Patients with bipolar disorder spend approximately half of their lives symptomatic and the majority of that time suffering from symptoms of depression, which complicates the accurate diagnosis of bipolar disorder. Challenges in the differential diagnosis of bipolar disorder and major depressive disorder are reviewed, and the clinical utility of several screening instruments is evaluated. The estimated lifetime prevalence of major depressive disorder (i.e., unipolar depression) is over 3 and one-half times that of bipolar spectrum disorders. The clinical presentation of a major depressive episode in a bipolar disorder patient does not differ substantially from that of a patient with major depressive disorder (unipolar depression). Therefore, it is not surprising that without proper screening and comprehensive evaluation many patients with bipolar disorder may be misdiagnosed with major depressive disorder (unipolar depression). In general, antidepressants have demonstrated little or no efficacy for depressive episodes associated with bipolar disorder, and treatment guidelines recommend using antidepressants only as an adjunct to mood stabilizers for patients with bipolar disorder. Thus, correct identification of bipolar disorder among patients who present with depression is critical for providing appropriate treatment and improving patient outcomes. Clinical characteristics indicative of bipolar disorder versus major depressive disorder identified in this review are based on group differences and may not apply to each individual patient. The overview of demographic and clinical characteristics provided by this review may help medical professionals distinguish between major depressive disorder and bipolar disorder. Several validated, easily administered screening instruments are available and can greatly improve the recognition of bipolar disorder in patients with depression. Copyright © 2014 Elsevier B.V. All rights reserved.

A report on older-age bipolar disorder from the International Society for Bipolar Disorders Task Force

DEFF Research Database (Denmark)

Sajatovic, Martha; Strejilevich, Sergio A; Gildengers, Ariel G

2015-01-01

, and shed light on issues of relevance to BD research across the lifespan. Although there is still a dearth of research and health efforts focused on older adults with BD, emerging data have brought some answers, innovative questions, and novel perspectives related to the notion of late onset, medical......OBJECTIVES: In the coming generation, older adults with bipolar disorder (BD) will increase in absolute numbers as well as proportion of the general population. This is the first report of the International Society for Bipolar Disorder (ISBD) Task Force on Older-Age Bipolar Disorder (OABD). METHODS...

Autonomous rexinoid death signaling is suppressed by converging signaling pathways in immature leukemia cells.

Science.gov (United States)

Benoit, G R; Flexor, M; Besançon, F; Altucci, L; Rossin, A; Hillion, J; Balajthy, Z; Legres, L; Ségal-Bendirdjian, E; Gronemeyer, H; Lanotte, M

2001-07-01

On their own, retinoid X receptor (RXR)-selective ligands (rexinoids) are silent in retinoic acid receptor (RAR)-RXR heterodimers, and no selective rexinoid program has been described as yet in cellular systems. We report here on the rexinoid signaling capacity that triggers apoptosis of immature promyelocytic NB4 cells as a default pathway in the absence of survival factors. Rexinoid-induced apoptosis displays all features of bona fide programmed cell death and is inhibited by RXR, but not RAR antagonists. Several types of survival signals block rexinoid-induced apoptosis. RARalpha agonists switch the cellular response toward differentiation and induce the expression of antiapoptosis factors. Activation of the protein kinase A pathway in the presence of rexinoid agonists induces maturation and blocks immature cell apoptosis. Addition of nonretinoid serum factors also blocks cell death but does not induce cell differentiation. Rexinoid-induced apoptosis is linked to neither the presence nor stability of the promyelocytic leukemia-RARalpha fusion protein and operates also in non-acute promyelocytic leukemia cells. Together our results support a model according to which rexinoids activate in certain leukemia cells a default death pathway onto which several other signaling paradigms converge. This pathway is entirely distinct from that triggered by RAR agonists, which control cell maturation and postmaturation apoptosis.

On Bipolar Valued Fuzzy k-Ideals in Hermirings

International Nuclear Information System (INIS)

Mahmood, T.; Ejaz, A.

2015-01-01

In this paper we discuss some results associated with bipolar valued fuzzy k -ideals of hermirings. We also define bipolar valued fuzzy k-intrinsic product and characterize k-hemiregular hermirings by using their bipolar valued fuzzy k -ideals. (author)

The Androgen Receptor Bridges Stem Cell-Associated Signaling Nodes in Prostate Stem Cells

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Alastair H. Davies

2016-01-01

Full Text Available The therapeutic potential of stem cells relies on dissecting the complex signaling networks that are thought to regulate their pluripotency and self-renewal. Until recently, attention has focused almost exclusively on a small set of “core” transcription factors for maintaining the stem cell state. It is now clear that stem cell regulatory networks are far more complex. In this review, we examine the role of the androgen receptor (AR in coordinating interactions between signaling nodes that govern the balance of cell fate decisions in prostate stem cells.

Bipolar spintronics: from spin injection to spin-controlled logic

International Nuclear Information System (INIS)

Zutic, Igor; Fabian, Jaroslav; Erwin, Steven C

2007-01-01

An impressive success of spintronic applications has been typically realized in metal-based structures which utilize magnetoresistive effects for substantial improvements in the performance of computer hard drives and magnetic random access memories. Correspondingly, the theoretical understanding of spin-polarized transport is usually limited to a metallic regime in a linear response, which, while providing a good description for data storage and magnetic memory devices, is not sufficient for signal processing and digital logic. In contrast, much less is known about possible applications of semiconductor-based spintronics and spin-polarized transport in related structures which could utilize strong intrinsic nonlinearities in current-voltage characteristics to implement spin-based logic. Here we discuss the challenges for realizing a particular class of structures in semiconductor spintronics: our proposal for bipolar spintronic devices in which carriers of both polarities (electrons and holes) contribute to spin-charge coupling. We formulate the theoretical framework for bipolar spin-polarized transport, and describe several novel effects in two- and three-terminal structures which arise from the interplay between nonequilibrium spin and equilibrium magnetization

Flow field bipolar plates in a proton exchange membrane fuel cell: Analysis & modeling

International Nuclear Information System (INIS)

Kahraman, Huseyin; Orhan, Mehmet F.

2017-01-01

Highlights: • Covers a comprehensive review of available flow field channel configurations. • Examines the main design considerations and limitations for a flow field network. • Explores the common materials and material properties used for flow field plates. • Presents a case study of step-by-step modeling for an optimum flow field design. - Abstract: This study investigates flow fields and flow field plates (bipolar plates) in proton exchange membrane fuel cells. In this regard, the main design considerations and limitations for a flow field network have been examined, along with a comprehensive review of currently available flow field channel configurations. Also, the common materials and material properties used for flow field plates have been explored. Furthermore, a case study of step-by-step modeling for an optimum flow field design has been presented in-details. Finally, a parametric study has been conducted with respect to many design and performance parameters in a flow field plate.

Exercising control over bipolar disorder.

Science.gov (United States)

Malhi, Gin S; Byrow, Yulisha

2016-11-01

Following extensive research exercise has emerged as an effective treatment for major depressive disorder, and it is now a recognised therapy alongside other interventions. In contrast, there is a paucity of research examining the therapeutic effects of exercise for those with bipolar disorder. Given that dysfunctional reward processing is central to bipolar disorder, research suggests that exercise can perhaps be framed as a reward-related event that may have the potential to precipitate a manic episode. The behavioural activation system (BAS) is a neurobehavioural system that is associated with responding to reward and provides an appropriate framework to theoretically examine and better understand the effects of exercise treatment on bipolar disorder. This article discusses recent research findings and provides an overview of the extant literature related to the neurobiological underpinnings of BAS and exercise as they relate to bipolar disorder. This is important clinically because depending on mood state in bipolar disorder, we postulate that exercise could be either beneficial or deleterious with positive or negative effects on the illness. Clearly, this complicates the evaluation of exercise as a potential treatment in terms of identifying its optimal characteristics in this population. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

A micro-scale model for predicting contact resistance between bipolar plate and gas diffusion layer in PEM fuel cells

Energy Technology Data Exchange (ETDEWEB)

Zhou, Y.; Lin, G.; Shih, A.J.; Hu, S.J. [Department of Mechanical Engineering, The University of Michigan, Ann Arbor, MI 48109-2125 (United States)

2007-01-01

Contact resistance between the bipolar plate (BPP) and the gas diffusion layer (GDL) in a proton exchange membrane (PEM) fuel cell constitutes a significant portion of the overall fuel cell electrical resistance under the normal operation conditions. Most current methods for contact resistance estimation are experimental and there is a lack of well developed theoretical methods. A micro-scale numerical model is developed to predict the electrical contact resistance between BPP and GDL by simulating the BPP surface topology and GDL structure and numerically determining the status for each contact spot. The total resistance and pressure are obtained by considering all contact spots as resistances in parallel and summing the results together. This model shows good agreements with experimental results. Influences of BPP surface roughness parameters on contact resistance are also studied. This model is beneficial in understanding the contact behavior between BPP and GDL and can be integrated with other fuel cell simulations to predict the overall performance of PEM fuel cells. (author)

Phantom phone signals: An investigation into the prevalence and predictors of imagined cell phone signals

NARCIS (Netherlands)

Tanis, M.A.; Beukeboom, C.J.; Hartmann, T.; Vermeulen, I.E.

2015-01-01

This paper aims to elucidate the peculiar phenomenon of imagined cell phone signals, or Phantom Phone Signals (PPS), which is defined as an individual's perception of a phone signal, indicating an incoming call, message, or social media notification, when in fact no such signal was transmitted. A

Wnt-β-Catenin Signaling Promotes the Maturation of Mast Cells

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Tomoko Yamaguchi

2016-01-01

Full Text Available Mast cells play an important role in the pathogenesis of allergic diseases. Immature mast cells migrate into peripheral tissues from the bone marrow and undergo complete maturation. Interestingly, mast cells have characteristics similar to hematopoietic stem cells (HSCs, such as self-renewal and c-kit expression. In HSCs, Wnt signaling is involved in their maintenance and differentiation. On the other hand, the relation between Wnt signaling and mast cell differentiation is poorly understood. To study whether Wnt signals play a role in the maturation of mast cells, we studied the effect of Wnt proteins on mast cell maturation of bone marrow-derived mast cells (BMMCs. The expression levels of CD81 protein and histidine decarboxylase mRNA and activity of mast cell-specific protease were all elevated in BMMCs treated with Wnt5a. In addition, Wnt5a induced the expression of Axin2 and TCF mRNA in BMMCs. These results showed that Wnt5a could promote the maturation of mast cells via the canonical Wnt signaling pathway and provide important insights into the molecular mechanisms underlying the differentiation of mast cells.

Calcium signaling properties of a thyrotroph cell line, mouse TαT1 cells.

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Tomić, Melanija; Bargi-Souza, Paula; Leiva-Salcedo, Elias; Nunes, Maria Tereza; Stojilkovic, Stanko S

2015-12-01

TαT1 cells are mouse thyrotroph cell line frequently used for studies on thyroid-stimulating hormone beta subunit gene expression and other cellular functions. Here we have characterized calcium-signaling pathways in TαT1 cells, an issue not previously addressed in these cells and incompletely described in native thyrotrophs. TαT1 cells are excitable and fire action potentials spontaneously and in response to application of thyrotropin-releasing hormone (TRH), the native hypothalamic agonist for thyrotrophs. Spontaneous electrical activity is coupled to small amplitude fluctuations in intracellular calcium, whereas TRH stimulates both calcium mobilization from intracellular pools and calcium influx. Non-receptor-mediated depletion of intracellular pool also leads to a prominent facilitation of calcium influx. Both receptor and non-receptor stimulated calcium influx is substantially attenuated but not completely abolished by inhibition of voltage-gated calcium channels, suggesting that depletion of intracellular calcium pool in these cells provides a signal for both voltage-independent and -dependent calcium influx, the latter by facilitating the pacemaking activity. These cells also express purinergic P2Y1 receptors and their activation by extracellular ATP mimics TRH action on calcium mobilization and influx. The thyroid hormone triiodothyronine prolongs duration of TRH-induced calcium spikes during 30-min exposure. These data indicate that TαT1 cells are capable of responding to natively feed-forward TRH signaling and intrapituitary ATP signaling with acute calcium mobilization and sustained calcium influx. Amplification of TRH-induced calcium signaling by triiodothyronine further suggests the existence of a pathway for positive feedback effects of thyroid hormones probably in a non-genomic manner. Published by Elsevier Ltd.

Signal peptide of eosinophil cationic protein is toxic to cells lacking signal peptide peptidase

International Nuclear Information System (INIS)

Wu, C.-M.; Chang, Margaret Dah-Tsyr

2004-01-01

Eosinophil cationic protein (ECP) is a toxin secreted by activated human eosinophils. The properties of mature ECP have been well studied but those of the signal peptide of ECP (ECPsp) are not clear. In this study, several chimeric proteins containing N-terminal fusion of ECPsp were generated, and introduced into Escherichia coli, Pichia pastoris, and human epidermoid carcinoma cell line A431 to study the function of ECPsp. We found that expression of ECPsp chimeric proteins inhibited the growth of E. coli and P. pastoris but not A431 cells. Primary sequence analysis and in vitro transcription/translation of ECPsp have revealed that it is a potential substrate for human signal peptide peptidase (hSPP), an intramembrane protease located in endoplasmic reticulum. In addition, knockdown of the hSPP mRNA expression in ECPsp-eGFP/A431 cells caused the growth inhibitory effect, whereas complementally expression of hSPP in P. pastoris system rescued the cell growth. Taken together, we have demonstrated that ECPsp is a toxic signal peptide, and expression of hSPP protects the cells from growth inhibition

[Circadian markers and genes in bipolar disorder].

Science.gov (United States)

Yeim, S; Boudebesse, C; Etain, B; Belliviera, F

2015-09-01

Bipolar disorder is a severe and complex multifactorial disease, characterized by alternance of acute episodes of depression and mania/hypomania, interspaced by euthymic periods. The etiological determinants of bipolar disorder yet, are still poorly understood. For the last 30 years, chronobiology is an important field of investigation to better understand the pathophysiology of bipolar disorder. We conducted a review using Medline, ISI Database, EMBase, PsyInfo up to January 2015, using the following keywords combinations: "mood disorder", "bipolar disorder", "depression", "unipolar disorder", "major depressive disorder", "affective disorder", for psychiatric conditions; and "circadian rhythms", "circadian markers", "circadian gene", "clock gene", "melatonin" for circadian rhythms. The search critera was presence of word in any field of the article. Quantitative and qualitative circadian abnormalities are associated with bipolar disorders both during acute episodes and euthymic periods, suggesting that these altered circadian rhythms may represent biological trait markers of the disorder. These circadian dysfunctions were assessed by various validated tools including polysomnography, actigraphy, sleep diaries, chronotype assessments and blood melatonin/cortisol measures. Other altered endogenous circadian activities have also been reported in bipolar patients, such as hormones secretion, core body temperature or fibroblasts activity. Moreover, these markers were also altered in healthy relatives of bipolar patients, suggesting a degree of heritability. Several genetic association studies have also showed associations between multiple circadian genes and bipolar disorder, such as CLOCK, ARTNL1, GSK3β, PER3, NPAS2, NR1D1, TIMELESS, RORA, RORB, and CSNK1ε. Thus, these circadian gene variants may contribute to the genetic susceptibility of the disease. Furthermore, the study of the clock system may help to better understand some phenotypic aspects like the

Interaction of Wnt Signaling with BMP/Smad Signaling during the Transition from Cell Proliferation to Myogenic Differentiation in Mouse Myoblast-Derived Cells

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Kumiko Terada

2013-01-01

Full Text Available Background. Wnt signaling is involved in muscle formation through β-catenin-dependent or -independent pathways, but interactions with other signaling pathways including transforming growth factor β/Smad have not been precisely elucidated. Results. As Wnt4 stimulates myogenic differentiation by antagonizing myostatin (GDF8 activity, we examined the role of Wnt4 signaling during muscle differentiation in the C2C12 myoblast cell line. Among several extrinsic signaling molecules examined in a microarray analysis of C2C12 cells during the transition from cell proliferation to differentiation after mitogen deprivation, bone morphogenetic protein 4 (BMP4 expression was prominently increased. Wnt4 overexpression had similar effects on BMP4 expression. BMP4 was able to inhibit muscle differentiation when added to the culture medium. BMP4 and noggin had no effects on the cellular localization of β-catenin induced by Wnt3a; however, the BMP4-induced phosphorylation of Smad1/5/8 was enhanced by Wnt4, but not by Wnt3a. The BMP antagonist noggin effectively stimulated muscle differentiation through binding to endogenous BMPs, and the effect of noggin was enhanced by the presence of Wnt3a and Wnt4. Conclusion. These results suggest that BMP/Smad pathways are modified through Wnt signaling during the transition from progenitor cell proliferation to myogenic differentiation, although Wnt/β-catenin signaling is not modified with BMP/Smad signaling.

New types of bipolar fuzzy sets in -semihypergroups

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Naveed Yaqoob

2016-04-01

Full Text Available The notion of bipolar fuzzy set was initiated by Lee (2000 as a generalization of the notion fuzzy sets and intuitionistic fuzzy sets, which have drawn attention of many mathematicians and computer scientists. In this paper, we initiate a study on bipolar ( , -fuzzy sets in -semihypergroups. By using the concept of bipolar ( , -fuzzy sets (Yaqoob and Ansari, 2013, we introduce the notion of bipolar ( , -fuzzy sub -semihypergroups (-hyperideals and bi--hyperideals and discuss some basic results on bipolar ( , -fuzzy sets in -semihypergroups. Furthermore, we define the bipolar fuzzy subset ,               and prove that if  ,       is a bipolar ( , -fuzzy sub -semihypergroup (resp., -hyperideal and bi--hyperideal of H; then ,               is also a bipolar ( , -fuzzy sub -semihypergroup (resp., -hyperideal and bi--hyperideal of H.

Classification of cognitive performance in bipolar disorder.

Science.gov (United States)

Sparding, Timea; Silander, Katja; Pålsson, Erik; Östlind, Josefin; Ekman, Carl Johan; Sellgren, Carl M; Joas, Erik; Hansen, Stefan; Landén, Mikael

2017-09-01

To understand the etiology of cognitive impairment associated with bipolar disorder, we need to clarify potential heterogeneity in cognitive functioning. To this end, we used multivariate techniques to study if the correlation structure of cognitive abilities differs between persons with bipolar disorder and controls. Clinically stable patients with bipolar disorder (type I: n = 64; type II: n = 44) and healthy controls (n = 86) were assessed with a wide range of cognitive tests measuring executive function, speed, memory, and verbal skills. Data were analysed with multivariate techniques. A distinct subgroup (∼30%) could be identified that performed significantly poorer on tests concerning memory function. This cognitive phenotype subgroup did not differ from the majority of bipolar disorder patients with respect to other demographic or clinical characteristics. Whereas the majority of patients performed similar to controls, a subgroup of patients with bipolar disorder differed substantially from healthy controls in the correlation pattern of low-level cognitive abilities. This suggests that cognitive impairment is not a general trait in bipolar disorder but characteristic of a cognitive subgroup. This has important clinical implications for cognitive rehabilitation and remediation.

Deep ion implantation for bipolar silicon devices; investigations into the use of the third dimension

International Nuclear Information System (INIS)

Mouthaan, A.J.

1986-01-01

This thesis covers various aspects of the use of deep ion implantations in digital bipolar circuits. It starts with the implications of the use of deep ion implantations for numerical process, device and circuit simulation. It shows the use of 1MeV boron and phosphorus implantations in the realization of a fully vertical IIL, here named Buried Injector Logic, which can also be used as static and dynamic memory device in several different configurations. The author presents a combined MOS-bipolar device, called the Charge Injection Device as a dynamic memory cell. Finally, deep ion implantations are used to realize a stack of photovoltaic cells that produces a multiple of the open circuit voltage of one photodiode. (Auth.)

RP58 Regulates the Multipolar-Bipolar Transition of Newborn Neurons in the Developing Cerebral Cortex

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Chiaki Ohtaka-Maruyama

2013-02-01

Full Text Available Accumulating evidence suggests that many brain diseases are associated with defects in neuronal migration, suggesting that this step of neurogenesis is critical for brain organization. However, the molecular mechanisms underlying neuronal migration remain largely unknown. Here, we identified the zinc-finger transcriptional repressor RP58 as a key regulator of neuronal migration via multipolar-to-bipolar transition. RP58−/− neurons exhibited severe defects in the formation of leading processes and never shifted to the locomotion mode. Cre-mediated deletion of RP58 using in utero electroporation in RP58flox/flox mice revealed that RP58 functions in cell-autonomous multipolar-to-bipolar transition, independent of cell-cycle exit. Finally, we found that RP58 represses Ngn2 transcription to regulate the Ngn2-Rnd2 pathway; Ngn2 knockdown rescued migration defects of the RP58−/− neurons. Our findings highlight the critical role of RP58 in multipolar-to-bipolar transition via suppression of the Ngn2-Rnd2 pathway in the developing cerebral cortex.

Light adaptation alters the source of inhibition to the mouse retinal OFF pathway

Science.gov (United States)

Mazade, Reece E.

2013-01-01

Sensory systems must avoid saturation to encode a wide range of stimulus intensities. One way the retina accomplishes this is by using both dim-light-sensing rod and bright-light-sensing cone photoreceptor circuits. OFF cone bipolar cells are a key point in this process, as they receive both excitatory input from cones and inhibitory input from AII amacrine cells via the rod pathway. However, in addition to AII amacrine cell input, other inhibitory inputs from cone pathways also modulate OFF cone bipolar cell light signals. It is unknown how these inhibitory inputs to OFF cone bipolar cells change when switching between rod and cone pathways or whether all OFF cone bipolar cells receive rod pathway input. We found that one group of OFF cone bipolar cells (types 1, 2, and 4) receive rod-mediated inhibitory inputs that likely come from the rod-AII amacrine cell pathway, while another group of OFF cone bipolar cells (type 3) do not. In both cases, dark-adapted rod-dominant light responses showed a significant contribution of glycinergic inhibition, which decreased with light adaptation and was, surprisingly, compensated by an increase in GABAergic inhibition. As GABAergic input has distinct timing and spatial spread from glycinergic input, a shift from glycinergic to GABAergic inhibition could significantly alter OFF cone bipolar cell signaling to downstream OFF ganglion cells. Larger GABAergic input could reflect an adjustment of OFF bipolar cell spatial inhibition, which may be one mechanism that contributes to retinal spatial sensitivity in the light. PMID:23926034

Adhesion signaling promotes protease‑driven polyploidization of glioblastoma cells.

Science.gov (United States)

Mercapide, Javier; Lorico, Aurelio

2014-11-01

An increase in ploidy (polyploidization) causes genomic instability in cancer. However, the determinants for the increased DNA content of cancer cells have not yet been fully elucidated. In the present study, we investigated whether adhesion induces polyploidization in human U87MG glioblastoma cells. For this purpose, we employed expression vectors that reported transcriptional activation by signaling networks implicated in cancer. Signaling activation induced by intercellular integrin binding elicited both extracellular signal‑regulated kinase (ERK) and Notch target transcription. Upon the prolonged activation of both ERK and Notch target transcription induced by integrin binding to adhesion protein, cell cultures accumulated polyploid cells, as determined by cell DNA content distribution analysis and the quantification of polynucleated cells. This linked the transcriptional activation induced by integrin adhesion to the increased frequency of polyploidization. Accordingly, the inhibition of signaling decreased the extent of polyploidization mediated by protease‑driven intracellular invasion. Therefore, the findings of this study indicate that integrin adhesion induces polyploidization through the stimulation of glioblastoma cell invasiveness.

[Bipolar disorders and anorexia nervosa: A clinical study].

Science.gov (United States)

Valentin, M; Radon, L; Duclos, J; Curt, F; Godart, N

2018-06-20

Anorexia nervosa is often accompanied by comorbid mood disorders, in particular depression, but individual or family history of bipolar disorders has not frequently been explored in anorexia nervosa. The objectives of the present study were: (1) to assess the frequency of bipolar disorders in patients with anorexia nervosa hospitalized in adolescence and in their parents, (2) to determine whether the patients with a personal or family history of bipolar disorders present particular characteristics in the way in which anorexia nervosa manifests itself, in their medical history, in the secondary diagnoses established, and in the treatments prescribed. Overall, 97 female patients aged 13 to 20 hospitalized for anorexia nervosa and their parents were assessed. The diagnoses of anorexia nervosa and bipolar disorders were established on the basis of DSM-IV-TR criteria. A high frequency of type II and type V bipolar disorders was observed. The patients with anorexia nervosa and presenting personal or family histories of bipolar disorder had an earlier onset of anorexia nervosa, more numerous hospitalizations, a longer time-lapse between anorexia nervosa onset and hospitalization, more suicide attempts and more psychiatric comorbidities. The occurrence of anorexia nervosa-bipolar disorders comorbidity appears to be considerable and linked to the severity of anorexia nervosa, raising the issue of the relationship between anorexia nervosa and bipolar disorders. Copyright © 2017. Published by Elsevier Masson SAS.

Social support and bipolar disorder

Directory of Open Access Journals (Sweden)

Paula Mendonça Studart

2015-08-01

Full Text Available Background Bipolar disorder is a chronic condition that affects the functioning of its carriers in many different ways, even when treated properly. Therefore, it’s also important to identify the psychosocial aspects that could contribute to an improvement of this population’s quality of life.Objective Carry out a literature review on the role of social support in cases of bipolar disorder.Method A research on the following online databases PubMed, Lilacs and SciELO was conducted by using the keywords “social support” or “social networks” and “mood disorders” or “bipolar disorder” or “affective disorder,” with no defined timeline.Results Only 13 studies concerning the topic of social support and BD were found in the search for related articles. Generally speaking, the results show low rates of social support for BD patients.Discussion Despite the growing interest in the overall functioning of patients with bipolar disorder, studies on social support are still rare. Besides, the existing studies on the subject use different methodologies, making it difficult to establish data comparisons.

Jasmonic acid signaling modulates ozone-induced hypersensitive cell death.

Science.gov (United States)

Rao, M V; Lee, H; Creelman, R A; Mullet, J E; Davis, K R

2000-09-01

Recent studies suggest that cross-talk between salicylic acid (SA)-, jasmonic acid (JA)-, and ethylene-dependent signaling pathways regulates plant responses to both abiotic and biotic stress factors. Earlier studies demonstrated that ozone (O(3)) exposure activates a hypersensitive response (HR)-like cell death pathway in the Arabidopsis ecotype Cvi-0. We now have confirmed the role of SA and JA signaling in influencing O(3)-induced cell death. Expression of salicylate hydroxylase (NahG) in Cvi-0 reduced O(3)-induced cell death. Methyl jasmonate (Me-JA) pretreatment of Cvi-0 decreased O(3)-induced H(2)O(2) content and SA concentrations and completely abolished O(3)-induced cell death. Cvi-0 synthesized as much JA as did Col-0 in response to O(3) exposure but exhibited much less sensitivity to exogenous Me-JA. Analyses of the responses to O(3) of the JA-signaling mutants jar1 and fad3/7/8 also demonstrated an antagonistic relationship between JA- and SA-signaling pathways in controlling the magnitude of O(3)-induced HR-like cell death.

Generation of short electrical pulses based on bipolar transistorsny

Directory of Open Access Journals (Sweden)

M. Gerding

2004-01-01

Full Text Available A system for the generation of short electrical pulses based on the minority carrier charge storage and the step recovery effect of bipolar transistors is presented. Electrical pulses of about 90 ps up to 800 ps duration are generated with a maximum amplitude of approximately 7V at 50Ω. The bipolar transistor is driven into saturation and the base-collector and base-emitter junctions become forward biased. The resulting fast switch-off edge of the transistor’s output signal is the basis for the pulse generation. The fast switching of the transistor occurs as a result of the minority carriers that have been injected and stored across the base-collector junction under forward bias conditions. If the saturated transistor is suddenly reverse biased the pn-junction will appear as a low impedance until the stored charge is depleted. Then the impedance will suddenly increase to its normal high value and the flow of current through the junction will turn to zero, abruptly. A differentiation of the output signal of the transistor results in two short pulses with opposite polarities. The differentiating circuit is implemented by a transmission line network, which mainly acts as a high pass filter. Both the transistor technology (pnp or npn and the phase of the transfer function of the differentating circuit influence the polarity of the output pulses. The pulse duration depends on the transistor parameters as well as on the transfer function of the pulse shaping network. This way of generating short electrical pulses is a new alternative for conventional comb generators based on steprecovery diodes (SRD. Due to the three-terminal structure of the transistor the isolation problem between the input and the output signal of the transistor network is drastically simplified. Furthermore the transistor is an active element in contrast to a SRD, so that its current gain can be used to minimize the power of the driving signal.

MAPK cascades in guard cell signal transduction

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Yuree eLee

2016-02-01

Full Text Available Guard cells form stomata on the epidermis and continuously respond to endogenous and environmental stimuli to fine-tune the gas exchange and transpirational water loss, processes which involve mitogen-activated protein kinase (MAPK cascades. MAPKs form three-tiered kinase cascades with MAPK kinases and MAPK kinase kinases, by which signals are transduced to the target proteins. MAPK cascade genes are highly conserved in all eukaryotes, and they play crucial roles in myriad developmental and physiological processes. MAPK cascades function during biotic and abiotic stress responses by linking extracellular signals received by receptors to cytosolic events and gene expression. In this review, we highlight recent findings and insights into MAPK-mediated guard cell signaling, including the specificity of MAPK cascades and the remaining questions.

Bipolar disorder and dementia: where is the link?

Science.gov (United States)

Masouy, Anaïs; Chopard, Gilles; Vandel, Pierre; Magnin, Eloi; Rumbach, Lucien; Sechter, Daniel; Haffen, Emmanuel

2011-03-01

Cognitive disorders appearing in the course of bipolar disease have been identified, and recent studies have defined the neuropsychological characteristics of this pathology, which includes attention, executive function, memory and language disorders. However, questions remain concerning the appearance of dementia symptoms over the course of bipolar disorder in certain patients: is it a chance association or is there a connection between bipolar disorders and dementia? If the latter hypothesis is considered, what is the nature of the dementia, which might be considered as a dementia specific to bipolar disorder? Current clinical, neuropsychological and cerebral imaging data are inconclusive, but similarities with frontotemporal dementia might be highlighted. Functional imaging studies might provide answers as well as more specific tests in neuropsychology. The cause of cognitive damage in bipolar disease also raises questions concerning a neurodevelopmental or neurodegenerative process, because several factors seem to influence cognition and these two processes might occur simultaneously. Long-term studies are necessary to determine whether cognitive deterioration in bipolar disease is stable or progressive. There might also be different neurobiological subgroups of patients with bipolar disease. © 2011 The Authors. Psychogeriatrics © 2011 Japanese Psychogeriatric Society.

[Detection of surface EMG signal using active electrode].

Science.gov (United States)

He, Qinghua; Peng, Chenglin; Wu, Baoming; Wang, He

2003-09-01

Research of surface electromyogram(EMG) signal is important in rehabilitation medicine, sport medicine and clinical diagnosis, accurate detection of signal is the base of quantitative analysis of surface EMG signal. In this article were discussed how to reduce possible noise in the detection of surface EMG. Considerations on the design of electrode unit were presented. Instrumentation amplifier AD620 was employed to design a bipolar active electrode for use in surface EMG detection. The experiments showed that active electrode could be used to improve signal/noise ratio, reduce noise and detect surface EMG signal effectively.

Wnt/β-catenin signaling regulates cancer stem cells in lung cancer A549 cells

International Nuclear Information System (INIS)

Teng, Ying; Wang, Xiuwen; Wang, Yawei; Ma, Daoxin

2010-01-01

Wnt/β-catenin signaling plays an important role not only in cancer, but also in cancer stem cells. In this study, we found that β-catenin and OCT-4 was highly expressed in cisplatin (DDP) selected A549 cells. Stimulating A549 cells with lithium chloride (LiCl) resulted in accumulation of β-catenin and up-regulation of a typical Wnt target gene cyclin D1. This stimulation also significantly enhanced proliferation, clone formation, migration and drug resistance abilities in A549 cells. Moreover, the up-regulation of OCT-4, a stem cell marker, was observed through real-time PCR and Western blotting. In a reverse approach, we inhibited Wnt signaling by knocking down the expression of β-catenin using RNA interference technology. This inhibition resulted in down-regulation of the Wnt target gene cyclin D1 as well as the proliferation, clone formation, migration and drug resistance abilities. Meanwhile, the expression of OCT-4 was reduced after the inhibition of Wnt/β-catenin signaling. Taken together, our study provides strong evidence that canonical Wnt signaling plays an important role in lung cancer stem cell properties, and it also regulates OCT-4, a lung cancer stem cell marker.

c-MPL provides tumor-targeted T-cell receptor-transgenic T cells with costimulation and cytokine signals.

Science.gov (United States)

Nishimura, Christopher D; Brenner, Daniel A; Mukherjee, Malini; Hirsch, Rachel A; Ott, Leah; Wu, Meng-Fen; Liu, Hao; Dakhova, Olga; Orange, Jordan S; Brenner, Malcolm K; Lin, Charles Y; Arber, Caroline

2017-12-21

Adoptively transferred T-cell receptor (TCR)-engineered T cells depend on host-derived costimulation and cytokine signals for their full and sustained activation. However, in patients with cancer, both signals are frequently impaired. Hence, we developed a novel strategy that combines both essential signals in 1 transgene by expressing the nonlymphoid hematopoietic growth factor receptor c-MPL (myeloproliferative leukemia), the receptor for thrombopoietin (TPO), in T cells. c-MPL signaling activates pathways shared with conventional costimulatory and cytokine receptor signaling. Thus, we hypothesized that host-derived TPO, present in the tumor microenvironment, or pharmacological c-MPL agonists approved by the US Food and Drug Administration could deliver both signals to c-MPL-engineered TCR-transgenic T cells. We found that c-MPL + polyclonal T cells expand and proliferate in response to TPO, and persist longer after adoptive transfer in immunodeficient human TPO-transgenic mice. In TCR-transgenic T cells, c-MPL activation enhances antitumor function, T-cell expansion, and cytokine production and preserves a central memory phenotype. c-MPL signaling also enables sequential tumor cell killing, enhances the formation of effective immune synapses, and improves antileukemic activity in vivo in a leukemia xenograft model. We identify the type 1 interferon pathway as a molecular mechanism by which c-MPL mediates immune stimulation in T cells. In conclusion, we present a novel immunotherapeutic strategy using c-MPL-enhanced transgenic T cells responding to either endogenously produced TPO (a microenvironment factor in hematologic malignancies) or c-MPL-targeted pharmacological agents. © 2017 by The American Society of Hematology.

Design of a 1-kWh bipolar nickel hydrogen battery

Science.gov (United States)

Cataldo, R. L.

1984-01-01

The design of a nickel hydrogen battery utilizing bipolar construction in a common pressure vessel is discussed. Design features are as follows: 40 ampere-hour capacity, 1 kWh stored energy as a 24 cell battery, 1.8 kW delivered in a LEO Cycle and maximum pulse power of 18.0 kW.

Curcumin blocks interleukin-1 signaling in chondrosarcoma cells.

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Thomas Kalinski

Full Text Available Interleukin (IL-1 signaling plays an important role in inflammatory processes, but also in malignant processes. The essential downstream event in IL-1 signaling is the activation of nuclear factor (NF-κB, which leads to the expression of several genes that are involved in cell proliferation, invasion, angiogenesis and metastasis, among them VEGF-A. As microenvironment-derived IL-1β is required for invasion and angiogenesis in malignant tumors, also in chondrosarcomas, we investigated IL-1β-induced signal transduction and VEGF-A expression in C3842 and SW1353 chondrosarcoma cells. We additionally performed in vitro angiogenesis assays and NF-κB-related gene expression analyses. Curcumin is a substance which inhibits IL-1 signaling very early by preventing the recruitment of IL-1 receptor associated kinase (IRAK to the IL-1 receptor. We demonstrate that IL-1 signaling and VEGF-A expression are blocked by Curcumin in chondrosarcoma cells. We further show that Curcumin blocks IL-1β-induced angiogenesis and NF-κB-related gene expression. We suppose that IL-1 blockade is an additional treatment option in chondrosarcoma, either by Curcumin, its derivatives or other IL-1 blocking agents.

Crammed signaling motifs in the T-cell receptor.

Science.gov (United States)

Borroto, Aldo; Abia, David; Alarcón, Balbino

2014-09-01

Although the T cell antigen receptor (TCR) is long known to contain multiple signaling subunits (CD3γ, CD3δ, CD3ɛ and CD3ζ), their role in signal transduction is still not well understood. The presence of at least one immunoreceptor tyrosine-based activation motif (ITAM) in each CD3 subunit has led to the idea that the multiplication of such elements essentially serves to amplify signals. However, the evolutionary conservation of non-ITAM sequences suggests that each CD3 subunit is likely to have specific non-redundant roles at some stage of development or in mature T cell function. The CD3ɛ subunit is paradigmatic because in a relatively short cytoplasmic sequence (∼55 amino acids) it contains several docking sites for proteins involved in intracellular trafficking and signaling, proteins whose relevance in T cell activation is slowly starting to be revealed. In this review we will summarize our current knowledge on the signaling effectors that bind directly to the TCR and we will propose a hierarchy in their response to TCR triggering. Copyright © 2014 Elsevier B.V. All rights reserved.

Paired structures and bipolar knowledge representation

DEFF Research Database (Denmark)

Montero, Javier; Bustince, Humberto; Franco, Camilo

In this strictly positional paper we propose a general approach to bipolar knowledge representation, where the meaning of concepts can be modelled by examining their decomposition into opposite and neutral categories. In particular, it is the semantic relationship between the opposite categories...... and at the same time the type of neutrality rising in between opposites. Based on this first level of bipolar knowledge representation, paired structures in fact offer the means to characterize a specific bipolar valuation scale depending on the meaning of the concept that has to be verified. In this sense...

Nrf2 regulates cellular behaviors and Notch signaling in oral squamous cell carcinoma cells.

Science.gov (United States)

Fan, Hong; Paiboonrungruan, Chorlada; Zhang, Xinyan; Prigge, Justin R; Schmidt, Edward E; Sun, Zheng; Chen, Xiaoxin

2017-11-04

Oxidative stress is known to play a pivotal role in the development of oral squamous cell carcinoma (OSCC). We have demonstrated that activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway has chemopreventive effects against oxidative stress-associated OSCC. However, Nrf2 have dual roles in cancer development; while it prevents carcinogenesis of normal cells, hyperactive Nrf2 also promotes the survival of cancer cells. This study is aimed to understand the function of Nrf2 in regulating cellular behaviors of OSCC cells, and the potential mechanisms through which Nrf2 facilitates OSCC. We established the Nrf2-overexpressing and Nrf2-knockdown OSCC cell lines, and examined the function of Nrf2 in regulating cell proliferation, migration, invasion, cell cycle and colony formation. Our data showed that Nrf2 overexpression promoted cancer phenotypes in OSCC cells, whereas Nrf2 silencing inhibited these phenotypes. In addition, Nrf2 positively regulated Notch signaling pathway in OSCC cells in vitro. Consistent with this observation, Nrf2 activation in Keap1 -/- mice resulted in not only hyperproliferation of squamous epithelial cells in mouse tongue as evidenced by increased expression of PCNA, but also activation of Notch signaling in these cells as evidenced by increased expression of NICD1 and Hes1. In conclusion, Nrf2 regulates cancer behaviors and Notch signaling in OSCC cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Toward a complex system understanding of bipolar disorder: A chaotic model of abnormal circadian activity rhythms in euthymic bipolar disorder.

Science.gov (United States)

Hadaeghi, Fatemeh; Hashemi Golpayegani, Mohammad Reza; Jafari, Sajad; Murray, Greg

2016-08-01

In the absence of a comprehensive neural model to explain the underlying mechanisms of disturbed circadian function in bipolar disorder, mathematical modeling is a helpful tool. Here, circadian activity as a response to exogenous daily cycles is proposed to be the product of interactions between neuronal networks in cortical (cognitive processing) and subcortical (pacemaker) areas of the brain. To investigate the dynamical aspects of the link between disturbed circadian activity rhythms and abnormalities of neurotransmitter functioning in frontal areas of the brain, we developed a novel mathematical model of a chaotic system which represents fluctuations in circadian activity in bipolar disorder as changes in the model's parameters. A novel map-based chaotic system was developed to capture disturbances in circadian activity across the two extreme mood states of bipolar disorder. The model uses chaos theory to characterize interplay between neurotransmitter functions and rhythm generation; it aims to illuminate key activity phenomenology in bipolar disorder, including prolonged sleep intervals, decreased total activity and attenuated amplitude of the diurnal activity rhythm. To test our new cortical-circadian mathematical model of bipolar disorder, we utilized previously collected locomotor activity data recorded from normal subjects and bipolar patients by wrist-worn actigraphs. All control parameters in the proposed model have an important role in replicating the different aspects of circadian activity rhythm generation in the brain. The model can successfully replicate deviations in sleep/wake time intervals corresponding to manic and depressive episodes of bipolar disorder, in which one of the excitatory or inhibitory pathways is abnormally dominant. Although neuroimaging research has strongly implicated a reciprocal interaction between cortical and subcortical regions as pathogenic in bipolar disorder, this is the first model to mathematically represent this

A Simulation Tool for Geometrical Analysis and Optimization of Fuel Cell Bipolar Plates: Development, Validation and Results

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Javier Pino

2009-07-01

Full Text Available Bipolar plates (BPs are one of the most important components in Proton Exchange Membrane Fuel Cells (PEMFC due to the numerous functions they perform. The objective of the research work described in this paper was to develop a simplified and validated method based on Computational Fluid Dynamics (CFD, aimed at the analysis and study of the influence of geometrical parameters of BPs on the operation of a cell. A complete sensibility analysis of the influence of dimensions and shape of the BP can be obtained through a simplified CFD model without including the complexity of other components of the PEMFC. This model is compared with the PEM Fuel Cell Module of the FLUENT software, which includes the physical and chemical phenomena relevant in PEMFCs. Results with both models regarding the flow field inside the channels and local current densities are obtained and compared. The results show that it is possible to use the simple model as a standard tool for geometrical analysis of BPs, and results of a sensitivity analysis using the simplified model are presented and discussed.

Wnt Signaling in Cancer Stem Cell Biology

NARCIS (Netherlands)

de Sousa E Melo, Felipe; Vermeulen, Louis

2016-01-01

Aberrant regulation of Wnt signaling is a common theme seen across many tumor types. Decades of research have unraveled the epigenetic and genetic alterations that result in elevated Wnt pathway activity. More recently, it has become apparent that Wnt signaling levels identify stem-like tumor cells

A signal processing analysis of Purkinje cells in vitro

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Ze'ev R Abrams

2010-05-01

Full Text Available Cerebellar Purkinje cells in vitro fire recurrent sequences of Sodium and Calcium spikes. Here, we analyze the Purkinje cell using harmonic analysis, and our experiments reveal that its output signal is comprised of three distinct frequency bands, which are combined using Amplitude and Frequency Modulation (AM/FM. We find that the three characteristic frequencies - Sodium, Calcium and Switching – occur in various combinations in all waveforms observed using whole-cell current clamp recordings. We found that the Calcium frequency can display a frequency doubling of its frequency mode, and the Switching frequency can act as a possible generator of pauses that are typically seen in Purkinje output recordings. Using a reversibly photo-switchable kainate receptor agonist, we demonstrate the external modulation of the Calcium and Switching frequencies. These experiments and Fourier analysis suggest that the Purkinje cell can be understood as a harmonic signal oscillator, enabling a higher level of interpretation of Purkinje signaling based on modern signal processing techniques.

Phospho-specific flow cytometry identifies aberrant signaling in indolent B-cell lymphoma

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Blix Egil S

2012-10-01

Full Text Available Abstract Background Knowledge about signaling pathways in malignant cells may provide prognostic and diagnostic information in addition to identify potential molecular targets for therapy. B-cell receptor (BCR and co-receptor CD40 signaling is essential for normal B cells, and there is increasing evidence that signaling via BCR and CD40 plays an important role in the pathogenesis of B-cell lymphoma. The aim of this study was to investigate basal and induced signaling in lymphoma B cells and infiltrating T cells in single-cell suspensions of biopsies from small cell lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL and marginal zone lymphoma (MZL patients. Methods Samples from untreated SLL/CLL and MZL patients were examined for basal and activation induced signaling by phospho-specific flow cytometry. A panel of 9 stimulation conditions targeting B and T cells, including crosslinking of the B cell receptor (BCR, CD40 ligand and interleukins in combination with 12 matching phospho-protein readouts was used to study signaling. Results Malignant B cells from SLL/CLL patients had higher basal levels of phosphorylated (p-SFKs, p-PLCγ, p-ERK, p-p38, p-p65 (NF-κB, p-STAT5 and p-STAT6, compared to healthy donor B cells. In contrast, anti-BCR induced signaling was highly impaired in SLL/CLL and MZL B cells as determined by low p-SFK, p-SYK and p-PLCγ levels. Impaired anti-BCR-induced p-PLCγ was associated with reduced surface expression of IgM and CD79b. Similarly, CD40L-induced p-ERK and p-p38 were also significantly reduced in lymphoma B cells, whereas p-p65 (NF-κB was equal to that of normal B cells. In contrast, IL-2, IL-7 and IL-15 induced p-STAT5 in tumor-infiltrating T cells were not different from normal T cells. Conclusions BCR signaling and CD40L-induced p-p38 was suppressed in malignant B cells from SLL/CLL and MZL patients. Single-cell phospho-specific flow cytometry for detection of basal as well as activation

Bipolar electrochemistry.

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Fosdick, Stephen E; Knust, Kyle N; Scida, Karen; Crooks, Richard M

2013-09-27

A bipolar electrode (BPE) is an electrically conductive material that promotes electrochemical reactions at its extremities (poles) even in the absence of a direct ohmic contact. More specifically, when sufficient voltage is applied to an electrolyte solution in which a BPE is immersed, the potential difference between the BPE and the solution drives oxidation and reduction reactions. Because no direct electrical connection is required to activate redox reactions, large arrays of electrodes can be controlled with just a single DC power supply or even a battery. The wireless aspect of BPEs also makes it possible to electrosynthesize and screen novel materials for a wide variety of applications. Finally, bipolar electrochemistry enables mobile electrodes, dubbed microswimmers, that are able to move freely in solution. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cell adhesion signaling regulates RANK expression in osteoclast precursors.

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Ayako Mochizuki

Full Text Available Cells with monocyte/macrophage lineage expressing receptor activator of NF-κB (RANK differentiate into osteoclasts following stimulation with the RANK ligand (RANKL. Cell adhesion signaling is also required for osteoclast differentiation from precursors. However, details of the mechanism by which cell adhesion signals induce osteoclast differentiation have not been fully elucidated. To investigate the participation of cell adhesion signaling in osteoclast differentiation, mouse bone marrow-derived macrophages (BMMs were used as osteoclast precursors, and cultured on either plastic cell culture dishes (adherent condition or the top surface of semisolid methylcellulose gel loaded in culture tubes (non-adherent condition. BMMs cultured under the adherent condition differentiated into osteoclasts in response to RANKL stimulation. However, under the non-adherent condition, the efficiency of osteoclast differentiation was markedly reduced even in the presence of RANKL. These BMMs retained macrophage characteristics including phagocytic function and gene expression profile. Lipopolysaccharide (LPS and tumor necrosis factor -αTNF-α activated the NF-κB-mediated signaling pathways under both the adherent and non-adherent conditions, while RANKL activated the pathways only under the adherent condition. BMMs highly expressed RANK mRNA and protein under the adherent condition as compared to the non-adherent condition. Also, BMMs transferred from the adherent to non-adherent condition showed downregulated RANK expression within 24 hours. In contrast, transferring those from the non-adherent to adherent condition significantly increased the level of RANK expression. Moreover, interruption of cell adhesion signaling by echistatin, an RGD-containing disintegrin, decreased RANK expression in BMMs, while forced expression of either RANK or TNFR-associated factor 6 (TRAF6 in BMMs induced their differentiation into osteoclasts even under the non

Lysosomal cysteine peptidases - Molecules signaling tumor cell death and survival.

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Pišlar, Anja; Perišić Nanut, Milica; Kos, Janko

2015-12-01

Lysosomal cysteine peptidases - cysteine cathepsins - are general intracellular protein-degrading enzymes that control also a variety of specific physiological processes. They can trigger irreversible events leading to signal transduction and activation of signaling pathways, resulting in cell survival and proliferation or cell death. In cancer cells, lysosomal cysteine peptidases are involved in multiple processes during malignant progression. Their translocation from the endosomal/lysosomal pathway to nucleus, cytoplasm, plasma membrane and extracellular space enables the activation and remodeling of a variety of tumor promoting proteins. Thus, lysosomal cysteine peptidases interfere with cytokine/chemokine signaling, regulate cell adhesion and migration and endocytosis, are involved in the antitumor immune response and apoptosis, and promote cell invasion, angiogenesis and metastasis. Further, lysosomal cysteine peptidases modify growth factors and receptors involved in tyrosine kinase dependent pathways such as MAPK, Akt and JNK, thus representing key signaling tools for the activation of tumor cell growth and proliferation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cognitive behavioral therapy for bipolar disorders

OpenAIRE

Lotufo Neto, Francisco

2004-01-01

Descrição dos objetivos e principais técnicas da terapia comportamental cognitiva usadas para a psicoterapia das pessoas com transtorno bipolar.Objectives and main techniques of cognitive behavior therapy for the treatment of bipolar disorder patients are described.

Allosteric conformational barcodes direct signaling in the cell.

Science.gov (United States)

Nussinov, Ruth; Ma, Buyong; Tsai, Chung-Jung; Csermely, Peter

2013-09-03

The cellular network is highly interconnected. Pathways merge and diverge. They proceed through shared proteins and may change directions. How are cellular pathways controlled and their directions decided, coded, and read? These questions become particularly acute when we consider that a small number of pathways, such as signaling pathways that regulate cell fates, cell proliferation, and cell death in development, are extensively exploited. This review focuses on these signaling questions from the structural standpoint and discusses the literature in this light. All co-occurring allosteric events (including posttranslational modifications, pathogen binding, and gain-of-function mutations) collectively tag the protein functional site with a unique barcode. The barcode shape is read by an interacting molecule, which transmits the signal. A conformational barcode provides an intracellular address label, which selectively favors binding to one partner and quenches binding to others, and, in this way, determines the pathway direction, and, eventually, the cell's response and fate. Copyright © 2013 Elsevier Ltd. All rights reserved.

Biological dysrhythm in remitted bipolar I disorder.

Science.gov (United States)

Iyer, Aishwarya; Palaniappan, Pradeep

2017-12-01

Recent treatment guidelines support treatment of biological rhythm abnormalities as a part of treatment of bipolar disorder, but still, literature examining various domains (Sleep, Activity, Social, and Eating) of biological rhythm and its clinical predictors are less. The main aim of our study is to compare various domains of biological rhythm among remitted bipolar I subjects and healthy controls. We also explored for any association between clinical variables and biological rhythm among bipolar subjects. 40 subjects with Bipolar I disorder and 40 healthy controls who met inclusion and exclusion criteria were recruited for the study. Diagnoses were ascertained by a qualified psychiatrist using MINI 5.0. Sociodemographic details, biological rhythm (BRIAN-Biological Rhythm Interview of assessment in Neuropsychiatry) and Sleep functioning (PSQI- Pittsburgh Sleep Quality Index) were assessed in all subjects. Mean age of the Bipolar subjects and controls were 41.25±11.84years and 38.25±11.25 years respectively. Bipolar subjects experienced more biological rhythm disturbance when compared to healthy controls (total BRIAN score being 34.25±9.36 vs 28.2±6.53) (p=0.002). Subsyndromal depressive symptoms (HDRS) had significant positive correlation with BRIAN global scores(r=0.368, p=0.02). Linear regression analysis showed that number of episodes which required hospitalization (β=0.601, t=3.106, P=0.004), PSQI (β=0.394, t=2.609, p=0.014), HDRS (β=0.376, t=2.34, t=0.036) explained 31% of variance in BRIAN scores in remitted bipolar subjects. Biological rhythm disturbances seem to persist even after clinical remission of bipolar illness. More studies to look into the impact of subsyndromal depressive symptoms on biological rhythm are needed. Copyright © 2017 Elsevier B.V. All rights reserved.

Ikaros limits follicular B cell activation by regulating B cell receptor signaling pathways

International Nuclear Information System (INIS)

Heizmann, Beate; Sellars, MacLean; Macias-Garcia, Alejandra; Chan, Susan; Kastner, Philippe

2016-01-01

The Ikaros transcription factor is essential for early B cell development, but its effect on mature B cells is debated. We show that Ikaros is required to limit the response of naive splenic B cells to B cell receptor signals. Ikaros deficient follicular B cells grow larger and enter cell cycle faster after anti-IgM stimulation. Unstimulated mutant B cells show deregulation of positive and negative regulators of signal transduction at the mRNA level, and constitutive phosphorylation of ERK, p38, SYK, BTK, AKT and LYN. Stimulation results in enhanced and prolonged ERK and p38 phosphorylation, followed by hyper-proliferation. Pharmacological inhibition of ERK and p38 abrogates the increased proliferative response of Ikaros deficient cells. These results suggest that Ikaros functions as a negative regulator of follicular B cell activation.

Ikaros limits follicular B cell activation by regulating B cell receptor signaling pathways

Energy Technology Data Exchange (ETDEWEB)

Heizmann, Beate [Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U964, CNRS UMR 7104, Université de Strasbourg, 67404 Illkirch (France); Sellars, MacLean [Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U964, CNRS UMR 7104, Université de Strasbourg, 67404 Illkirch (France); David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States); Macias-Garcia, Alejandra [Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U964, CNRS UMR 7104, Université de Strasbourg, 67404 Illkirch (France); Institute for Medical Engineering and Science at MIT, Cambridge, MA 02139 (United States); Chan, Susan, E-mail: scpk@igbmc.fr [Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U964, CNRS UMR 7104, Université de Strasbourg, 67404 Illkirch (France); Kastner, Philippe, E-mail: scpk@igbmc.fr [Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U964, CNRS UMR 7104, Université de Strasbourg, 67404 Illkirch (France); Faculté de Médecine, Université de Strasbourg, Strasbourg (France)

2016-02-12

The Ikaros transcription factor is essential for early B cell development, but its effect on mature B cells is debated. We show that Ikaros is required to limit the response of naive splenic B cells to B cell receptor signals. Ikaros deficient follicular B cells grow larger and enter cell cycle faster after anti-IgM stimulation. Unstimulated mutant B cells show deregulation of positive and negative regulators of signal transduction at the mRNA level, and constitutive phosphorylation of ERK, p38, SYK, BTK, AKT and LYN. Stimulation results in enhanced and prolonged ERK and p38 phosphorylation, followed by hyper-proliferation. Pharmacological inhibition of ERK and p38 abrogates the increased proliferative response of Ikaros deficient cells. These results suggest that Ikaros functions as a negative regulator of follicular B cell activation.

Decreased expression of Sprouty2 in the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder: a correlation with BDNF expression.

Directory of Open Access Journals (Sweden)

Anilkumar Pillai

Full Text Available BACKGROUND: Current theories on the pathophysiology of schizophrenia suggest altered brain plasticity such as decreased neural proliferation and migration, delayed myelination, and abnormal synaptic modeling, in the brain of subjects with schizophrenia. Though functional alterations in BDNF, which plays important role in neuroplasticity, are implicated in many abnormalities found in schizophrenia, the regulatory mechanism(s involved in the abnormal signaling of BDNF in schizophrenia is not clear. The present study investigated whether Sprouty2, a regulator of growth factor signaling, is abnormally expressed in schizophrenia, and is associated with the changes in BDNF mRNA in this disorder. The potential effect of antipsychotic drugs on Sprouty2 expression was tested in adult rats. METHODS AND FINDINGS: Sprouty2 and BDNF gene expression were analyzed in dorsolateral prefrontal cortex samples from the Stanley Array Collection. Quantitative real-time PCR analysis of RNA in 100 individuals (35 with schizophrenia, 31 with bipolar disorder, and 34 psychiatrically normal controls showed significantly decreased expression of Sprouty2 and BDNF in both schizophrenia and bipolar disorder. Moreover, a significant correlation between these two genes existed in control, schizophrenia and bipolar subjects. Long-term treatment with antipsychotic drugs, haloperidol and olanzapine, showed differential effects on both Sprouty2 and BDNF mRNA and protein levels in the frontal cortex of rats. CONCLUSION: These findings demonstrating decreased expression of Sprouty2 associated with changes in BDNF, suggest the possibility that these decreases are secondary to treatment rather than to factors that are significant in the disease process of either schizophrenia and/or bipolar disorder. Further exploration of Sprouty2-related signal transduction pathways may be helpful to design novel treatment strategies for these disorders.

Neutron–gamma discrimination based on bipolar trapezoidal pulse shaping using FPGAs in NE213

International Nuclear Information System (INIS)

Esmaeili-sani, Vahid; Moussavi-zarandi, Ali; Akbar-ashrafi, Nafiseh; Boghrati, Behzad; Afarideh, Hossein

2012-01-01

A technique employing neutron–gamma pulse shape discrimination (PSD) system that overcomes pile up limitations of previous methods to distinguish neutrons from gammas in scintillation detectors is described. The output signals of detectors were digitized and processed with a data acquisition system based on bipolar trapezoidal pulse shaping using Field programmable gate arrays (FPGA). FPGAs are capable of doing complex discrete signal processing algorithms with clock rates above 100 MHz. Their low cost, ease of use and selected dedicated hardware make them an ideal option for spectrometer systems.

Neutron-gamma discrimination based on bipolar trapezoidal pulse shaping using FPGAs in NE213

Energy Technology Data Exchange (ETDEWEB)

Esmaeili-sani, Vahid, E-mail: vaheed_esmaeely80@yahoo.com [Department of Nuclear Engineering and Physics, Amirkabir University of Technology, P.O. Box 4155-4494, Tehran (Iran, Islamic Republic of); Moussavi-zarandi, Ali; Akbar-ashrafi, Nafiseh; Boghrati, Behzad; Afarideh, Hossein [Department of Nuclear Engineering and Physics, Amirkabir University of Technology, P.O. Box 4155-4494, Tehran (Iran, Islamic Republic of)

2012-12-01

A technique employing neutron-gamma pulse shape discrimination (PSD) system that overcomes pile up limitations of previous methods to distinguish neutrons from gammas in scintillation detectors is described. The output signals of detectors were digitized and processed with a data acquisition system based on bipolar trapezoidal pulse shaping using Field programmable gate arrays (FPGA). FPGAs are capable of doing complex discrete signal processing algorithms with clock rates above 100 MHz. Their low cost, ease of use and selected dedicated hardware make them an ideal option for spectrometer systems.

Assessing Granger causality in electrophysiological data: the importance of bipolar derivations

Directory of Open Access Journals (Sweden)

Amy eTrongnetrpunya

2016-01-01

Full Text Available Multielectrode voltage data are usually recorded against a common reference. Such data are frequently used without further treatment to assess patterns of functional connectivity between neuronal populations and between brain areas. It is important to note from the outset that such an approach is valid only when the reference electrode is nearly electrically silent. In practice, however, the reference electrode is generally not electrically silent, thereby adding a common signal to the recorded data. Volume conduction further complicates the problem. In this study we demonstrate the adverse effects of common signals on the estimation of Granger causality, which is a statistical measure used to infer synaptic transmission and information flow in neural circuits from multielectrode data. We further test the hypothesis that the problem can be overcome by utilizing bipolar derivations where the difference between two nearby electrodes is taken and treated as a representation of local neural activity. Simulated data generated by a neuronal network model where the connectivity pattern is known were considered first. This was followed by analyzing data from three experimental preparations where a priori predictions regarding the patterns of causal interactions can be made: (1 laminar recordings from the hippocampus of an anesthetized rat during theta rhythm, (2 laminar recordings from V4 of an awake-behaving macaque monkey during alpha rhythm, and (3 ECoG recordings from electrode arrays implanted in the middle temporal lobe and prefrontal cortex of an epilepsy patient during fixation. For both simulation and experimental analysis the results show that bipolar derivations yield the expected connectivity patterns whereas the untreated data (referred to as unipolar signals do not. In addition, current source density signals, where applicable, yield results that are close to the expected connectivity patterns, whereas the commonly practiced average re

A bipolar clamp mechanism for activation of Jak-family protein tyrosine kinases.

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Dipak Barua

2009-04-01

Full Text Available Most cell surface receptors for growth factors and cytokines dimerize in order to mediate signal transduction. For many such receptors, the Janus kinase (Jak family of non-receptor protein tyrosine kinases are recruited in pairs and juxtaposed by dimerized receptor complexes in order to activate one another by trans-phosphorylation. An alternative mechanism for Jak trans-phosphorylation has been proposed in which the phosphorylated kinase interacts with the Src homology 2 (SH2 domain of SH2-B, a unique adaptor protein with the capacity to homo-dimerize. Building on a rule-based kinetic modeling approach that considers the concerted nature and combinatorial complexity of modular protein domain interactions, we examine these mechanisms in detail, focusing on the growth hormone (GH receptor/Jak2/SH2-Bbeta system. The modeling results suggest that, whereas Jak2-(SH2-Bbeta(2-Jak2 heterotetramers are scarcely expected to affect Jak2 phosphorylation, SH2-Bbeta and dimerized receptors synergistically promote Jak2 trans-activation in the context of intracellular signaling. Analysis of the results revealed a unique mechanism whereby SH2-B and receptor dimers constitute a bipolar 'clamp' that stabilizes the active configuration of two Jak2 molecules in the same macro-complex.

Coping and personality in older patients with bipolar disorder.

Science.gov (United States)

Schouws, Sigfried N T M; Paans, Nadine P G; Comijs, Hannie C; Dols, Annemiek; Stek, Max L

2015-09-15

Little is known about coping styles and personality traits in older bipolar patients. Adult bipolar patients show a passive coping style and higher neuroticism scores compared to the general population. Our aim is to investigate personality traits and coping in older bipolar patients and the relationship between coping and personality. 75 Older patients (age > 60) with bipolar I or II disorder in a euthymic mood completed the Utrecht Coping List and the NEO Personality Inventory FFI and were compared to normative data. Older bipolar patients show more passive coping styles compared to healthy elderly. Their personality traits are predominated by openness, in contrast conscientiousness and altruism are relatively sparse. Neuroticism was related to passive coping styles, whereas conscientiousness was related to an active coping style. Older bipolar patients have more passive coping styles. Their personality is characterized by openness and relatively low conscientiousness and altruism. Our sample represents a survival cohort; this may explain the differences in personality traits between older patients in this study and in adult bipolar patients in other studies. The association between coping styles and personality traits is comparable to reports of younger adult patients with bipolar disorder. Longitudinal studies are warranted to explore if coping and personality change with ageing in bipolar patients and to determine which coping style is most effective in preventing mood episodes. Copyright © 2015 Elsevier B.V. All rights reserved.

The nature of surround-induced depolarizing responses in goldfish cones

NARCIS (Netherlands)

Kraaij, D. A.; Spekreijse, H.; Kamermans, M.

2000-01-01

Cones in the vertebrate retina project to horizontal and bipolar cells and the horizontal cells feedback negatively to cones. This organization forms the basis for the center/surround organization of the bipolar cells, a fundamental step in the visual signal processing. Although the surround

Amperometric Adhesion Signals of Liposomes, Cells and Droplets

OpenAIRE

Ivošević DeNardis, N.; Žutić, V.; Svetličić, V.; Frkanec, R.

2009-01-01

Individual soft microparticles (liposomes, living cells and organic droplets) in aqueous media are characterized by their adhesion signals using amperometry at the dropping mercury electrode. We confirmed that the general mechanism established for adhesion of hydrocarbon droplets and cells is valid as well for liposome adhesion within a wide range of surface charge densities. Incidents and shape of adhesion signals in liposome suspensions reflect liposome polydispersity, surface charge den...

The role of sleep in bipolar disorder

Directory of Open Access Journals (Sweden)

Gold AK

2016-06-01

Full Text Available Alexandra K Gold,1 Louisa G Sylvia,1,2 1Department of Psychiatry, Massachusetts General Hospital, 2Harvard Medical School, Boston, MA, USA Abstract: Bipolar disorder is a serious mental illness characterized by alternating periods of elevated and depressed mood. Sleep disturbances in bipolar disorder are present during all stages of the condition and exert a negative impact on overall course, quality of life, and treatment outcomes. We examine the partnership between circadian system (process C functioning and sleep–wake homeostasis (process S on optimal sleep functioning and explore the role of disruptions in both systems on sleep disturbances in bipolar disorder. A convergence of evidence suggests that sleep problems in bipolar disorder result from dysregulation across both process C and process S systems. Biomarkers of depressive episodes include heightened fragmentation of rapid eye movement (REM sleep, reduced REM latency, increased REM density, and a greater percentage of awakenings, while biomarkers of manic episodes include reduced REM latency, greater percentage of stage I sleep, increased REM density, discontinuous sleep patterns, shortened total sleep time, and a greater time awake in bed. These findings highlight the importance of targeting novel treatments for sleep disturbance in bipolar disorder. Keywords: bipolar disorder, circadian rhythms, sleep–wake homeostasis

MET signalling in primary colon epithelial cells leads to increased transformation irrespective of aberrant Wnt signalling

Science.gov (United States)

Boon, E M J; Kovarikova, M; Derksen, P W B; van der Neut, R

2005-01-01

It has been shown that in hereditary and most sporadic colon tumours, components of the Wnt pathway are mutated. The Wnt target MET has been implicated in the development of colon cancer. Here, we show that overexpression of wild-type or a constitutively activated form of MET in colon epithelial cells leads to increased transformation irrespective of Wnt signalling. Fetal human colon epithelial cells without aberrant Wnt signalling were transfected with wild-type or mutated MET constructs. Expression of these constructs leads to increased phosphorylation of MET and its downstream targets PKB and MAPK. Upon stimulation with HGF, the expression of E-cadherin is downregulated in wild-type MET-transfected cells, whereas cells expressing mutated MET show low E-cadherin levels independent of stimulation with ligand. This implies a higher migratory propensity of these cells. Furthermore, fetal human colon epithelial cells expressing the mutated form of MET have colony-forming capacity in soft agar, while cells expressing wild-type MET show an intermediate phenotype. Subcutaneous injection of mutated MET-transfected cells in nude mice leads to the formation of tumours within 12 days in all mice injected. At this time point, mock-transfected cells do not form tumours, while wild-type MET-transfected cells form subcutaneous tumours in one out of five mice. We thus show that MET signalling can lead to increased transformation of colon epithelial cells independent of Wnt signalling and in this way could play an essential role in the onset and progression of colorectal cancer. PMID:15785735

Climatic factors and bipolar affective disorder

DEFF Research Database (Denmark)

Christensen, Ellen Margrethe; Larsen, Jens Knud; Gjerris, Annette

2008-01-01

In bipolar disorder, the factors provoking a new episode are unknown. As a seasonal variation has been noticed, it has been suggested that weather conditions may play a role. The aim of the study was to elucidate whether meteorological parameters influence the development of new bipolar phases....... A group of patients with at least three previous hospitalizations for bipolar disorder was examined every 3 months for up to 3 years. At each examination an evaluation of the affective phase was made according to the Hamilton Depression Scale (HAM-D(17)), and the Bech-Rafaelsen Mania Rating Scale (MAS......). In the same period, daily recordings from the Danish Meteorological Institute were received. We found no correlations between onset of bipolar episodes [defined as MAS score of 11 or more (mania) and as HAM-D(17) score of 12 or more (depression)] and any meteorological parameters. We found a statistical...

HIV-infected persons with bipolar disorder are less aware of memory deficits than HIV-infected persons without bipolar disorder

OpenAIRE

Blackstone, K; Tobin, A; Posada, C; Gouaux, B; Grant, I; Moore, DJ

2012-01-01

Episodic memory deficits are common in HIV infection and bipolar disorder, but patient insight into such deficits remains unclear. Thirty-four HIV-infected individuals without bipolar disorder (HIV+/BD-) and 47 HIV+ individuals with comorbid bipolar disorder (HIV+/BD+) were administered the Hopkins Verbal Learning Test-Revised and the Brief Visuospatial Memory Test-Revised to examine objective learning/memory functioning. Subjective memory complaints were assessed via the memory s ubscale of ...

Retinoic acid signalling in thymocytes regulates T cell development

DEFF Research Database (Denmark)

Wendland, Kerstin; Sitnik, Katarzyna Maria; Kotarsky, Knut

. Here, using a RA sensitive reporter mouse model, we demonstrate that endogenous RAR responses are induced in CD69+CD4+CD8lo and CD69+CD4+CD8+ thymocytes undergoing positive selection and lineage commitment, and continue to be present in both CD4+ and CD8+ single positive (SP) cells, with RA signaling...... further enhanced in recently generated CD69+ CD4+ SP cells. To address the potential biological significance of RA signaling in developing thymocytes, we evaluated T cell development in CD4Cre-dnRAR mice, where RA signaling is blocked in thymocytes from the CD4+CD8+ double positive (DP) stage onwards due...

Toward a Valid Animal Model of Bipolar Disorder: How the Research Domain Criteria Help Bridge the Clinical-Basic Science Divide.

Science.gov (United States)

Cosgrove, Victoria E; Kelsoe, John R; Suppes, Trisha

2016-01-01

Bipolar disorder is a diagnostically heterogeneous disorder, although mania emerges as a distinct phenotype characterized by elevated mood and increased activity or energy. While bipolar disorder's cyclicity is difficult to represent in animals, models of mania have begun to decode its fundamental underlying neurobiology. When psychostimulants such as amphetamine or cocaine are administered to rodents, a resulting upsurge of motor activity is thought to share face and predictive validity with mania in humans. Studying black Swiss mice, which inherently exhibit proclivity for reward seeking and risk taking, also has yielded some insight. Further, translating the biology of bipolar disorder in humans into animal models has led to greater understanding of roles for candidate biological systems such as the GRIK2 and CLOCK genes, as well as the extracellular signal-related kinase pathway involved in the pathophysiology of the illness. The National Institute of Mental Health Research Domain Criteria initiative seeks to identify building blocks of complex illnesses like bipolar disorder in hopes of uncovering the neurobiology of each, as well as how each fits together to produce syndromes like bipolar disorder or why so many mental illnesses co-occur together. Research Domain Criteria-driven preclinical models of isolated behaviors and domains involved in mania and bipolar disorder will ultimately inform movement toward nosology supported by neurobiology. Copyright © 2016 Society of Biological Psychiatry. All rights reserved.

Dynamic multiprotein assemblies shape the spatial structure of cell signaling.

Science.gov (United States)

Nussinov, Ruth; Jang, Hyunbum

2014-01-01

Cell signaling underlies critical cellular decisions. Coordination, efficiency as well as fail-safe mechanisms are key elements. How the cell ensures that these hallmarks are at play are important questions. Cell signaling is often viewed as taking place through discrete and cross-talking pathways; oftentimes these are modularized to emphasize distinct functions. While simple, convenient and clear, such models largely neglect the spatial structure of cell signaling; they also convey inter-modular (or inter-protein) spatial separation that may not exist. Here our thesis is that cell signaling is shaped by a network of multiprotein assemblies. While pre-organized, the assemblies and network are loose and dynamic. They contain transiently-associated multiprotein complexes which are often mediated by scaffolding proteins. They are also typically anchored in the membrane, and their continuum may span the cell. IQGAP1 scaffolding protein which binds proteins including Raf, calmodulin, Mek, Erk, actin, and tens more, with actin shaping B-cell (and likely other) membrane-anchored nanoclusters and allosterically polymerizing in dynamic cytoskeleton formation, and Raf anchoring in the membrane along with Ras, provides a striking example. The multivalent network of dynamic proteins and lipids, with specific interactions forming and breaking, can be viewed as endowing gel-like properties. Collectively, this reasons that efficient, productive and reliable cell signaling takes place primarily through transient, preorganized and cooperative protein-protein interactions spanning the cell rather than stochastic, diffusion-controlled processes. Copyright © 2014 Elsevier Ltd. All rights reserved.

Intercellular signaling through secreted proteins induces free-energy gradient-directed cell movement.

Science.gov (United States)

Kravchenko-Balasha, Nataly; Shin, Young Shik; Sutherland, Alex; Levine, R D; Heath, James R

2016-05-17

Controlling cell migration is important in tissue engineering and medicine. Cell motility depends on factors such as nutrient concentration gradients and soluble factor signaling. In particular, cell-cell signaling can depend on cell-cell separation distance and can influence cellular arrangements in bulk cultures. Here, we seek a physical-based approach, which identifies a potential governed by cell-cell signaling that induces a directed cell-cell motion. A single-cell barcode chip (SCBC) was used to experimentally interrogate secreted proteins in hundreds of isolated glioblastoma brain cancer cell pairs and to monitor their relative motions over time. We used these trajectories to identify a range of cell-cell separation distances where the signaling was most stable. We then used a thermodynamics-motivated analysis of secreted protein levels to characterize free-energy changes for different cell-cell distances. We show that glioblastoma cell-cell movement can be described as Brownian motion biased by cell-cell potential. To demonstrate that the free-energy potential as determined by the signaling is the driver of motion, we inhibited two proteins most involved in maintaining the free-energy gradient. Following inhibition, cell pairs showed an essentially random Brownian motion, similar to the case for untreated, isolated single cells.

Suicide attempts and clinical features of bipolar patients.

Science.gov (United States)

Berkol, Tonguç D; İslam, Serkan; Kırlı, Ebru; Pınarbaşı, Rasim; Özyıldırım, İlker

2016-06-01

To identify clinical predictors of suicide attempts in patients with bipolar disorder. This study included bipolar patients who were treated in the Psychiatry Department, Haseki Training and Research Hospital, Istanbul, Turkey, between 2013 and 2014; an informed consent was obtained from the participants. Two  hundred and eighteen bipolar patients were assessed by using the structured clinical interview for Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) Axis-I (SCID-I) in order to detect all possible psychiatric comorbid diagnoses. Clinical predictors of suicide attempts were examined in attempters and non-attempters. The study design was retrospective. The lifetime suicide attempt rate for the entire sample was 19.2%. Suicide attempters with bipolar disorder had more lifetime comorbidity of eating disorder. Female gender and family history of mood disorder were significant predictors for suicide attempts. There was no difference between groups in terms of bipolar disorder subtype, onset age of bipolar disorder, total number of episodes, first and predominant episode type, suicide history in first degree relatives, severity of episodes, and hospitalization and being psychotic. Our study revealed that female gender, family history of mood disorder, and eating disorder are more frequent in bipolar patients with at least one suicide attempt.

Perceived parental rearing of bipolar offspring

NARCIS (Netherlands)

Reichart, C. G.; van der Ende, J.; Hillegers, M. H. J.; Wals, M.; Bongers, I. L.; Nolen, W. A.; Ormel, J.; Verhulst, F. C.

Objective: To explore the impact of growing up with a parent with a bipolar disorder. First, we compared parental rearing behavior perceived by young adult offspring of bipolar parents with parental rearing behavior perceived by same aged young adults from the general population. Secondly, we

Combinations of genetic variants associated with bipolar disorder

DEFF Research Database (Denmark)

Mellerup, Erling; Andreassen, Ole A; Bennike, Bente

2017-01-01

The main objective of the study was to find genetic variants that in combination are significantly associated with bipolar disorder. In previous studies of bipolar disorder, combinations of three and four single nucleotide polymorphisms (SNP) genotypes taken from 803 SNPs were analyzed, and five...... clusters of combinations were found to be significantly associated with bipolar disorder. In the present study, combinations of ten SNP genotypes taken from the same 803 SNPs were analyzed, and one cluster of combinations was found to be significantly associated with bipolar disorder. Combinations from......, heterozygote or variant homozygote. In the combinations containing 10 SNP genotypes almost all the genotypes were the normal homozygote. Such a finding may indicate that accumulation in the genome of combinations containing few SNP genotypes may be a risk factor for bipolar disorder when those combinations...

Low hydrostatic head electrolyte addition to fuel cell stacks

International Nuclear Information System (INIS)

Kothmann, R.E.

1983-01-01

A fuel cell and system for supply electrolyte, as well as fuel and an oxidant to a fuel cell stack having at least two fuel cells, each of the cells having a pair of spaced electrodes and a matrix sandwiched therebetween, fuel and oxidant paths associated with a bipolar plate separating each pair of adjacent fuel cells and an electrolyte fill path for adding electrolyte to the cells and wetting said matrices. Electrolyte is flowed through the fuel cell stack in a back and forth fashion in a path in each cell substantially parallel to one face of opposite faces of the bipolar plate exposed to one of the electrodes and the matrices to produce an overall head uniformly between cells due to frictional pressure drop in the path for each cell free of a large hydrostatic head to thereby avoid flooding of the electrodes. The bipolar plate is provided with channels forming paths for the flow of the fuel and oxidant on opposite faces thereof, and the fuel and the oxidant are flowed along a first side of the bipolar plate and a second side of the bipolar plate through channels formed into the opposite faces of the bipolar plate, the fuel flowing through channels formed into one of the opposite faces and the oxidant flowing through channels formed into the other of the opposite faces

Bipolar magnetic semiconductor in silicene nanoribbons

International Nuclear Information System (INIS)

Farghadan, Rouhollah

2017-01-01

Highlights: • A new electronic phase for silicene nanoribbon in the presence of electric and magnetic fields. • Bipolar magnetic semiconductor with controllable spin-flip and spin-conserved gaps in silicene. • Robust bipolar magnetic semiconductor features in a rough silicene. • Perfect and reversible spin polarization in silicene nanoribbon junctions. - Abstract: A theoretical study was presented on generation of spin polarization in silicene nanoribbons using the single-band tight-binding approximation and the non-equilibrium Green’s function formalism. We focused on the effect of electric and exchange magnetic fields on the spin-filter capabilities of zigzag-edge silicene nanoribbons in the presence of the intrinsic spin-orbit interaction. The results show that a robust bipolar magnetic semiconductor with controllable spin-flip and spin-conserved gaps can be obtained when exchange magnetic and electric field strengths are both larger than the intrinsic spin-orbit interaction. Therefore, zigzag silicene nanoribbons could act as bipolar and perfect spin filter devices with a large spin-polarized current and a reversible spin polarization in the vicinity of the Fermi energy. We also investigated the effect of edge roughness and found that the bipolar magnetic semiconductor features are robust against edge disorder in silicene nanoribbon junctions. These results may be useful in multifunctional spin devices based on silicene nanoribbons.

Bipolar magnetic semiconductor in silicene nanoribbons

Energy Technology Data Exchange (ETDEWEB)

Farghadan, Rouhollah, E-mail: rfarghadan@kashanu.ac.ir

2017-08-01

Highlights: • A new electronic phase for silicene nanoribbon in the presence of electric and magnetic fields. • Bipolar magnetic semiconductor with controllable spin-flip and spin-conserved gaps in silicene. • Robust bipolar magnetic semiconductor features in a rough silicene. • Perfect and reversible spin polarization in silicene nanoribbon junctions. - Abstract: A theoretical study was presented on generation of spin polarization in silicene nanoribbons using the single-band tight-binding approximation and the non-equilibrium Green’s function formalism. We focused on the effect of electric and exchange magnetic fields on the spin-filter capabilities of zigzag-edge silicene nanoribbons in the presence of the intrinsic spin-orbit interaction. The results show that a robust bipolar magnetic semiconductor with controllable spin-flip and spin-conserved gaps can be obtained when exchange magnetic and electric field strengths are both larger than the intrinsic spin-orbit interaction. Therefore, zigzag silicene nanoribbons could act as bipolar and perfect spin filter devices with a large spin-polarized current and a reversible spin polarization in the vicinity of the Fermi energy. We also investigated the effect of edge roughness and found that the bipolar magnetic semiconductor features are robust against edge disorder in silicene nanoribbon junctions. These results may be useful in multifunctional spin devices based on silicene nanoribbons.

Single-cell analysis reveals a link between CD3- and CD59-mediated signaling pathways in Jurkat T cells

International Nuclear Information System (INIS)

Lipp, A. M.

2012-01-01

Elevation of intracellular free calcium concentration ([Ca2+]i) is a key signal during T cell activation and is commonly used as a read-out parameter for stimulation of T cell signaling. Upon T cell stimulation a variety of calcium signals is produced by individual cells of the T cell population and the type of calcium signal strongly influences cell fate decisions. The heterogeneous nature of T cells is masked in ensemble measurements, which highlights the need for single-cell measurements. In this study we used single-cell calcium measurements in Jurkat cells to investigate signaling pathways, which are triggered by different proteins, namely CD3 and CD59. By application of an automated cluster algorithm the presented assay provides unbiased analysis of a large data set of individual calcium time traces generated by the whole cell population. By using this method we could demonstrate that the Jurkat population generates heterogeneous calcium signals in a stimulus-dependent manner. Furthermore, our data revealed the existence of a link between CD3- and CD59-mediated signaling pathways. Single-cell calcium measurements in Jurkat cells expressing different levels of the T cell receptor (TCR) complex indicated that CD59-mediated calcium signaling is critically dependent on TCR surface expression levels. In addition, triggering CD59-mediated calcium signaling resulted in down-regulation of TCR surface expression levels, which is known to happen upon direct TCR triggering too. Moreover, by using siRNA-mediated protein knock-downs and protein knock-out Jurkat mutants we could show that CD3- and CD59-mediated calcium signaling require identical key proteins. We therefore explored by which mechanism CD59-mediated signaling couples into TCR-mediated signaling. Fluorescence recovery after photobleaching (FRAP) experiments and live-cell protein-protein interaction assays provided no evidence of a direct physical interaction between CD3- and CD59-mediated signaling pathways

Personality disorder symptom severity predicts onset of mood episodes and conversion to bipolar I disorder in individuals with bipolar spectrum disorder.

Science.gov (United States)

Ng, Tommy H; Burke, Taylor A; Stange, Jonathan P; Walshaw, Patricia D; Weiss, Rachel B; Urosevic, Snezana; Abramson, Lyn Y; Alloy, Lauren B

2017-04-01

Although personality disorders (PDs) are highly comorbid with bipolar spectrum disorders (BSDs), little longitudinal research has been conducted to examine the prospective impact of PD symptoms on the course of BSDs. The aim of this study is to examine whether PD symptom severity predicts shorter time to onset of bipolar mood episodes and conversion to bipolar I disorder over time among individuals with less severe BSDs. Participants (n = 166) with bipolar II disorder, cyclothymia, or bipolar disorder not otherwise specified completed diagnostic interview assessments of PD symptoms and self-report measures of mood symptoms at baseline. They were followed prospectively with diagnostic interviews every 4 months for an average of 3.02 years. Cox proportional hazard regression analyses indicated that overall PD symptom severity significantly predicted shorter time to onset of hypomanic (hazard ratio [HR] = 1.42; p conversion to bipolar I disorder (HR = 2.51; p conversion to bipolar I disorder (HR = 2.77; p < .001), whereas cluster C severity (HR = 1.56; p < .001) predicted shorter time to onset of major depressive episodes. These results support predisposition models in suggesting that PD symptoms may act as a risk factor for a more severe course of BSDs. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Signal transduction events in aluminum-induced cell death in tomato suspension cells

NARCIS (Netherlands)

Iakimova, E.T.; Kapchina-Toteva, V.M.; Woltering, E.J.

2007-01-01

In this study, some of the signal transduction events involved in AlCl3-induced cell death in tomato (Lycopersicon esculentum Mill.) suspension cells were elucidated. Cells treated with 100 ¿M AlCl3 showed typical features of programmed cell death (PCD) such as nuclear and cytoplasmic condensation.

Bipolar Disorder and Alcoholism: Are They Related?

Science.gov (United States)

... Are they related? Is there a connection between bipolar disorder and alcoholism? Answers from Daniel K. Hall-Flavin, M.D. Bipolar disorder and alcoholism often occur together. Although the association ...

N-wasp is essential for the negative regulation of B cell receptor signaling.

Directory of Open Access Journals (Sweden)

Chaohong Liu

2013-11-01

Full Text Available Negative regulation of receptor signaling is essential for controlling cell activation and differentiation. In B-lymphocytes, the down-regulation of B-cell antigen receptor (BCR signaling is critical for suppressing the activation of self-reactive B cells; however, the mechanism underlying the negative regulation of signaling remains elusive. Using genetically manipulated mouse models and total internal reflection fluorescence microscopy, we demonstrate that neuronal Wiskott-Aldrich syndrome protein (N-WASP, which is coexpressed with WASP in all immune cells, is a critical negative regulator of B-cell signaling. B-cell-specific N-WASP gene deletion causes enhanced and prolonged BCR signaling and elevated levels of autoantibodies in the mouse serum. The increased signaling in N-WASP knockout B cells is concurrent with increased accumulation of F-actin at the B-cell surface, enhanced B-cell spreading on the antigen-presenting membrane, delayed B-cell contraction, inhibition in the merger of signaling active BCR microclusters into signaling inactive central clusters, and a blockage of BCR internalization. Upon BCR activation, WASP is activated first, followed by N-WASP in mouse and human primary B cells. The activation of N-WASP is suppressed by Bruton's tyrosine kinase-induced WASP activation, and is restored by the activation of SH2 domain-containing inositol 5-phosphatase that inhibits WASP activation. Our results reveal a new mechanism for the negative regulation of BCR signaling and broadly suggest an actin-mediated mechanism for signaling down-regulation.

Brain Region and Cell Type Transcripts for Informative Diagnostics

Science.gov (United States)

2010-09-01

related with neurological condition and is on average larger in patients with schizophrenia and bipolar disorder. The blue circle region represents the...in a number of neurological conditions. Furthermore, this region is usually larger for schizophrenia , bipolar disorder, and Alzheimer’s disease...pathways such as calcium signaling pathway, mapK signaling pathway, Gaba pathway, and long- term depression pathways etc., are confirmed pathways through

Psychopharmacological treatment of psychotic mania and psychotic bipolar depression compared to non-psychotic mania and non-psychotic bipolar depression.

Science.gov (United States)

Bjørklund, Louise B; Horsdal, Henriette T; Mors, Ole; Gasse, Christiane; Østergaard, Søren D

2017-09-01

An evidence base for the treatment of mania and bipolar depression with psychotic symptoms is lacking. Nevertheless, clinicians may have a preference for treating episodes of bipolar disorder with or without psychotic symptoms in different ways, which is likely to reflect notions of differential efficacy of treatments between these subtypes. This study aimed to investigate whether the psychopharmacological treatment of psychotic and non-psychotic episodes of mania and bipolar depression, respectively, differs in clinical practice. We conducted a register-based study assessing the psychopharmacological treatment of all individuals receiving their first diagnosis of mania or bipolar depression between 2010 and 2012. The psychopharmacological treatment within 3 months following the time of diagnosis was considered. Potential differences in psychopharmacological treatment between the psychotic and non-psychotic subtypes of mania and bipolar depression, respectively, were investigated by means of Pearson's χ 2 test and logistic regression adjusted for sex and age at diagnosis of bipolar disorder. A total of 827 patients were included in the analyses. The adjusted odds ratio (aOR) for treatment with an antipsychotic was 1.71 (95% confidence interval [CI]: 1.18-2.48, Pbipolar depression. The aOR for treatment with the combination of an antipsychotic and an anticonvulsant was 1.60 (95% CI: 1.06-2.43, Pbipolar psychotic depression. It would be of interest to conduct studies evaluating whether antipsychotics represent the superior pharmacological treatment for psychotic mania and psychotic bipolar depression. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.