Agonist-stimulated cobalt uptake provides selective visualization of neurons expressing AMPA- or kainate-type glutamate receptors in the retina.

PubMed

Pourcho, Roberta G; Qin, Pu; Goebel, Dennis J; Fyk-Kolodziej, Bozena

2002-12-16

Fast-acting excitatory neurotransmission in the retina is mediated primarily by glutamate, acting at alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) -selective and kainate-selective receptors. To localize these sites of action, cat retinas were stimulated with either AMPA or kainate and processed for histochemical visualization of cobalt uptake through calcium-permeable channels. Treatment with both agonists resulted in staining of A- and B-type horizontal cells and several types of OFF cone bipolar cells; there was no evidence for staining of ON cone bipolar cells or rod bipolar cells. The subpopulations of OFF cone bipolar cells differed in their responses with two distinct types that stained heavily with cobalt after exposure to AMPA and three different types that were preferentially labeled after exposure to kainate. Although many amacrine and ganglion cells appeared to respond to both agonists, AII amacrine cells were stained after stimulation by AMPA but not by kainate. The OFF cone bipolar cells that exhibit AMPA-stimulated cobalt uptake were found to have a high level of correspondence with cells that show immunocytochemical staining for the AMPA-selective glutamate receptor subunits GluR1 and GluR2/3. Similarly, the cone bipolar cells exhibiting kainate-stimulated cobalt uptake resemble those that are immunoreactive for the kainate subunit GluR5. The results indicate that, whereas many retinal neurons express both AMPA and kainate receptors, AII amacrine cells and subpopulations of OFF cone bipolar cells are limited to the expression of either AMPA or kainate receptors. This differential expression may contribute to the unique character of transmission by these cell types. Copyright 2002 Wiley-Liss, Inc.

Mechanisms creating transient and sustained photoresponses in mammalian retinal ganglion cells

PubMed Central

Zhao, Xiwu; Jaeckel, Elizabeth R.; Chervenak, Andrew P.

2017-01-01

Retinal neurons use sustained and transient light responses to encode visual stimuli of different frequency ranges, but the underlying mechanisms remain poorly understood. In particular, although earlier studies in retinal ganglion cells (RGCs) proposed seven potential mechanisms, all seven have since been disputed, and it remains unknown whether different RGC types use different mechanisms or how many mechanisms are used by each type. Here, we conduct a comprehensive survey in mice and rats of 12 candidate mechanisms that could conceivably produce tonic rod/cone-driven ON responses in intrinsically photosensitive RGCs (ipRGCs) and transient ON responses in three types of direction-selective RGCs (TRHR+, Hoxd10+ ON, and Hoxd10+ ON-OFF cells). We find that the tonic kinetics of ipRGCs arises from their substantially above-threshold resting potentials, input from sustained ON bipolar cells, absence of amacrine cell inhibition of presynaptic ON bipolar cells, and mGluR7-mediated maintenance of light-evoked glutamatergic input. All three types of direction-selective RGCs receive input from transient ON bipolar cells, and each type uses additional strategies to promote photoresponse transience: presynaptic inhibition and dopaminergic modulation for TRHR+ cells, center/surround antagonism and relatively negative resting potentials for Hoxd10+ ON cells, and presynaptic inhibition for Hoxd10+ ON-OFF cells. We find that the sustained nature of ipRGCs’ rod/cone-driven responses depends neither on melanopsin nor on N-methyl-d-aspartate (NMDA) receptors, whereas the transience of the direction-selective cells’ responses is influenced neither by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor desensitization nor by glutamate uptake. For all cells, we further rule out spike frequency adaptation and intracellular Ca2+ as determinants of photoresponse kinetics. In conclusion, different RGC types use diverse mechanisms to produce sustained or transient light responses. Parenthetically, we find evidence in both mice and rats that the kinetics of light-induced mGluR6 deactivation determines whether an ON bipolar cell responds tonically or transiently to light. PMID:28153865

WAVE2-Abi2 complex controls growth cone activity and regulates the multipolar-bipolar transition as well as the initiation of glia-guided migration.

PubMed

Xie, Min-Jue; Yagi, Hideshi; Kuroda, Kazuki; Wang, Chen-Chi; Komada, Munekazu; Zhao, Hong; Sakakibara, Akira; Miyata, Takaki; Nagata, Koh-Ichi; Oka, Yuichiro; Iguchi, Tokuichi; Sato, Makoto

2013-06-01

Glia-guided migration (glia-guided locomotion) during radial migration is a characteristic yet unique mode of migration. In this process, the directionality of migration is predetermined by glial processes and not by growth cones. Prior to the initiation of glia-guided migration, migrating neurons transform from multipolar to bipolar, but the molecular mechanisms underlying this multipolar-bipolar transition and the commencement of glia-guided migration are not fully understood. Here, we demonstrate that the multipolar-bipolar transition is not solely a cell autonomous event; instead, the interaction of growth cones with glial processes plays an essential role. Time-lapse imaging with lattice assays reveals the importance of vigorously active growth cones in searching for appropriate glial scaffolds, completing the transition, and initiating glia-guided migration. These growth cone activities are regulated by Abl kinase and Cdk5 via WAVE2-Abi2 through the phosphorylation of tyrosine 150 and serine 137 of WAVE2. Neurons that do not display such growth cone activities are mispositioned in a more superficial location in the neocortex, suggesting the significance of growth cones for the final location of the neurons. This process occurs in spite of the "inside-out" principle in which later-born neurons are situated more superficially.

Deafferented Adult Rod Bipolar Cells Create New Synapses with Photoreceptors to Restore Vision

PubMed Central

Hovhannisyan, Anahit; Kung, Jennifer; Lee, Seungjun; Lee, Dae Yeong; Huie, Philip; Dalal, Roopa; Palanker, Daniel

2017-01-01

Upon degeneration of photoreceptors in the adult retina, interneurons, including bipolar cells, exhibit a plastic response leading to their aberrant rewiring. Photoreceptor reintroduction has been suggested as a potential approach to sight restoration, but the ability of deafferented bipolar cells to establish functional synapses with photoreceptors is poorly understood. Here we use photocoagulation to selectively destroy photoreceptors in adult rabbits while preserving the inner retina. We find that rods and cones shift into the ablation zone over several weeks, reducing the blind spot at scotopic and photopic luminances. During recovery, rod and cone bipolar cells exhibit markedly different responses to deafferentation. Rod bipolar cells extend their dendrites to form new synapses with healthy photoreceptors outside the lesion, thereby restoring visual function in the deafferented retina. Secretagogin-positive cone bipolar cells did not exhibit such obvious dendritic restructuring. These findings are encouraging to the idea of photoreceptor reintroduction for vision restoration in patients blinded by retinal degeneration. At the same time, they draw attention to the postsynaptic side of photoreceptor reintroduction; various bipolar cell types, representing different visual pathways, vary in their response to the photoreceptor loss and in their consequent dendritic restructuring. SIGNIFICANCE STATEMENT Loss of photoreceptors during retinal degeneration results in permanent visual impairment. Strategies for vision restoration based on the reintroduction of photoreceptors inherently rely on the ability of the remaining retinal neurons to correctly synapse with new photoreceptors. We show that deafferented bipolar cells in the adult mammalian retina can reconnect to rods and cones and restore retinal sensitivity at scotopic and photopic luminances. Rod bipolar cells extend their dendrites to form new synapses with healthy rod photoreceptors. These findings support the idea that bipolar cells might be able to synapse with reintroduced photoreceptors, thereby restoring vision in patients blinded by retinal degeneration. PMID:28373392

Stereotyped Synaptic Connectivity Is Restored during Circuit Repair in the Adult Mammalian Retina.

PubMed

Beier, Corinne; Palanker, Daniel; Sher, Alexander

2018-06-04

Proper function of the central nervous system (CNS) depends on the specificity of synaptic connections between cells of various types. Cellular and molecular mechanisms responsible for the establishment and refinement of these connections during development are the subject of an active area of research [1-6]. However, it is unknown if the adult mammalian CNS can form new type-selective synapses following neural injury or disease. Here, we assess whether selective synaptic connections can be reestablished after circuit disruption in the adult mammalian retina. The stereotyped circuitry at the first synapse in the retina, as well as the relatively short distances new neurites must travel compared to other areas of the CNS, make the retina well suited to probing for synaptic specificity during circuit reassembly. Selective connections between short-wavelength sensitive cone photoreceptors (S-cones) and S-cone bipolar cells provides the foundation of the primordial blue-yellow vision, common to all mammals [7-18]. We take advantage of the ground squirrel retina, which has a one-to-one S-cone-to-S-cone-bipolar-cell connection, to test if this connectivity can be reestablished following local photoreceptor loss [8, 19]. We find that after in vivo selective photoreceptor ablation, deafferented S-cone bipolar cells expand their dendritic trees. The new dendrites randomly explore the proper synaptic layer, bypass medium-wavelength sensitive cone photoreceptors (M-cones), and selectively synapse with S-cones. However, non-connected dendrites are not pruned back to resemble unperturbed S-cone bipolar cells. We show, for the first time, that circuit repair in the adult mammalian retina can recreate stereotypic selective wiring. Copyright © 2018 Elsevier Ltd. All rights reserved.

Deafferented Adult Rod Bipolar Cells Create New Synapses with Photoreceptors to Restore Vision.

PubMed

Beier, Corinne; Hovhannisyan, Anahit; Weiser, Sydney; Kung, Jennifer; Lee, Seungjun; Lee, Dae Yeong; Huie, Philip; Dalal, Roopa; Palanker, Daniel; Sher, Alexander

2017-04-26

Upon degeneration of photoreceptors in the adult retina, interneurons, including bipolar cells, exhibit a plastic response leading to their aberrant rewiring. Photoreceptor reintroduction has been suggested as a potential approach to sight restoration, but the ability of deafferented bipolar cells to establish functional synapses with photoreceptors is poorly understood. Here we use photocoagulation to selectively destroy photoreceptors in adult rabbits while preserving the inner retina. We find that rods and cones shift into the ablation zone over several weeks, reducing the blind spot at scotopic and photopic luminances. During recovery, rod and cone bipolar cells exhibit markedly different responses to deafferentation. Rod bipolar cells extend their dendrites to form new synapses with healthy photoreceptors outside the lesion, thereby restoring visual function in the deafferented retina. Secretagogin-positive cone bipolar cells did not exhibit such obvious dendritic restructuring. These findings are encouraging to the idea of photoreceptor reintroduction for vision restoration in patients blinded by retinal degeneration. At the same time, they draw attention to the postsynaptic side of photoreceptor reintroduction; various bipolar cell types, representing different visual pathways, vary in their response to the photoreceptor loss and in their consequent dendritic restructuring. SIGNIFICANCE STATEMENT Loss of photoreceptors during retinal degeneration results in permanent visual impairment. Strategies for vision restoration based on the reintroduction of photoreceptors inherently rely on the ability of the remaining retinal neurons to correctly synapse with new photoreceptors. We show that deafferented bipolar cells in the adult mammalian retina can reconnect to rods and cones and restore retinal sensitivity at scotopic and photopic luminances. Rod bipolar cells extend their dendrites to form new synapses with healthy rod photoreceptors. These findings support the idea that bipolar cells might be able to synapse with reintroduced photoreceptors, thereby restoring vision in patients blinded by retinal degeneration. Copyright © 2017 the authors 0270-6474/17/374635-10$15.00/0.

Contributions of Rod and Cone Pathways to Retinal Direction Selectivity Through Development

PubMed Central

Rosa, Juliana M.; Morrie, Ryan D.; Baertsch, Hans C.

2016-01-01

Direction selectivity is a robust computation across a broad stimulus space that is mediated by activity of both rod and cone photoreceptors through the ON and OFF pathways. However, rods, S-cones, and M-cones activate the ON and OFF circuits via distinct pathways and the relative contribution of each to direction selectivity is unknown. Using a variety of stimulation paradigms, pharmacological agents, and knockout mice that lack rod transduction, we found that inputs from the ON pathway were critical for strong direction-selective (DS) tuning in the OFF pathway. For UV light stimulation, the ON pathway inputs to the OFF pathway originated with rod signaling, whereas for visible stimulation, the ON pathway inputs to the OFF pathway originated with both rod and M-cone signaling. Whole-cell voltage-clamp recordings revealed that blocking the ON pathway reduced directional tuning in the OFF pathway via a reduction in null-side inhibition, which is provided by OFF starburst amacrine cells (SACs). Consistent with this, our recordings from OFF SACs confirmed that signals originating in the ON pathway contribute to their excitation. Finally, we observed that, for UV stimulation, ON contributions to OFF DS tuning matured earlier than direct signaling via the OFF pathway. These data indicate that the retina uses multiple strategies for computing DS responses across different colors and stages of development. SIGNIFICANCE STATEMENT The retina uses parallel pathways to encode different features of the visual scene. In some cases, these distinct pathways converge on circuits that mediate a distinct computation. For example, rod and cone pathways enable direction-selective (DS) ganglion cells to encode motion over a wide range of light intensities. Here, we show that although direction selectivity is robust across light intensities, motion discrimination for OFF signals is dependent upon ON signaling. At eye opening, ON directional tuning is mature, whereas OFF DS tuning is significantly reduced due to a delayed maturation of S-cone to OFF cone bipolar signaling. These results provide evidence that the retina uses multiple strategies for computing DS responses across different stimulus conditions. PMID:27629718

LRIT3 is essential to localize TRPM1 to the dendritic tips of depolarizing bipolar cells and may play a role in cone synapse formation

PubMed Central

Neuillé, Marion; Morgans, Catherine W.; Cao, Yan; Orhan, Elise; Michiels, Christelle; Sahel, José-Alain; Audo, Isabelle; Duvoisin, Robert M.; Martemyanov, Kirill A.; Zeitz, Christina

2016-01-01

Mutations in LRIT3 lead to complete congenital stationary night blindness (cCSNB). The exact role of LRIT3 in ON-bipolar cell signaling cascade remains to be elucidated. Recently, we have characterized a novel mouse model lacking Lrit3 (no b-wave 6, (Lrit3nob6/nob6)), which displays similar abnormalities as patients with cCSNB with LRIT3 mutations. Here we compare the localization of components of the ON-bipolar cell signaling cascade in wild-type and Lrit3nob6/nob6 retinal sections by immunofluorescence confocal microscopy. An anti-LRIT3 antibody was generated. Immunofluorescent staining of LRIT3 in wild-type mice revealed a specific punctate labeling in the outer plexiform layer (OPL), which was absent in Lrit3nob6/nob6 mice. LRIT3 did not colocalize with ribeye or calbindin but colocalized with mGluR6. TRPM1 staining was severely decreased at the dendritic tips of all depolarizing bipolar cells in Lrit3nob6/nob6 mice. mGluR6, GPR179, RGS7, RGS11 and Gβ5 immunofluorescence was absent at the dendritic tips of cone ON-bipolar cells in Lrit3nob6/nob6 mice, while it was present at the dendritic tips of rod bipolar cells. Furthermore, PNA labeling was severely reduced in the OPL in Lrit3nob6/nob6 mice. This study confirmed the localization of LRIT3 at the dendritic tips of depolarizing bipolar cells in mouse retina and demonstrated the dependence of TRPM1 localization on the presence of LRIT3. Since tested components of the ON-bipolar cell signaling cascade and PNA revealed disrupted localization, an additional function of LRIT3 in cone synapse formation is suggested. These results point to a possibly different regulation of the mGluR6 signaling cascade between rod and cone ON-bipolar cells. PMID:25997951

Mapping nonlinear receptive field structure in primate retina at single cone resolution

PubMed Central

Li, Peter H; Greschner, Martin; Gunning, Deborah E; Mathieson, Keith; Sher, Alexander; Litke, Alan M; Paninski, Liam

2015-01-01

The function of a neural circuit is shaped by the computations performed by its interneurons, which in many cases are not easily accessible to experimental investigation. Here, we elucidate the transformation of visual signals flowing from the input to the output of the primate retina, using a combination of large-scale multi-electrode recordings from an identified ganglion cell type, visual stimulation targeted at individual cone photoreceptors, and a hierarchical computational model. The results reveal nonlinear subunits in the circuity of OFF midget ganglion cells, which subserve high-resolution vision. The model explains light responses to a variety of stimuli more accurately than a linear model, including stimuli targeted to cones within and across subunits. The recovered model components are consistent with known anatomical organization of midget bipolar interneurons. These results reveal the spatial structure of linear and nonlinear encoding, at the resolution of single cells and at the scale of complete circuits. DOI: http://dx.doi.org/10.7554/eLife.05241.001 PMID:26517879

Center/surround organization of retinal bipolar cells: High correlation of fundamental responses of center and surround to sinusoidal contrasts

PubMed Central

Burkhardt, Dwight A.; Bartoletti, Theodore M.; Thoreson, Wallace B.

2012-01-01

Receptive field organization of cone-driven bipolar cells was investigated by intracellular recording in the intact light-adapted retina of the tiger salamander (Ambystoma tigrinum). Centered spots and concentric annuli of optimum dimensions were used to selectively stimulate the receptive field center and surround with sinusoidal modulations of contrast at 3 Hz. At low contrasts, responses of both the center and surround of both ON and OFF bipolar cells were linear, showing high gain and thus contrast enhancement relative to cones. The contrast/response curves for the fundamental response, measured by a Fast Fourier Transform, reached half maximum amplitude quickly at 13% contrast followed by saturation at high contrasts. The variation of the normalized amplitude of the center and surround responses was remarkably similar, showing linear regression over the entire response range with very high correlations, r2 = 0.97 for both ON and OFF cells. The contrast/response curves of both center and surround for both ON and OFF cells were well fit (r2 = 0.98) by an equation for single-site binding. In about half the cells studied, the nonlinear waveforms of center and surround could be brought into coincidence by scaling and shifting the surround response in time. This implies that a nonlinearity, common to both center and surround, occurs after polarity inversion at the cone feedback synapse. Evidence from paired whole-cell recordings between single cones and OFF bipolar cells suggests that substantial nonlinearity is not due to transmission at the cone synapse but instead arises from intrinsic bipolar cell and network mechanisms. When sinusoidal contrast modulations were applied to the center and surround simultaneously, clear additivity was observed for small responses in both ON and OFF cells, whereas the interaction was strikingly nonadditive for large responses. The contribution of the surround was then greatly reduced, suggesting attenuation at the cone feedback synapse. PMID:21439110

Synaptic noise is an information bottleneck in the inner retina during dynamic visual stimulation

PubMed Central

Freed, Michael A; Liang, Zhiyin

2014-01-01

In daylight, noise generated by cones determines the fidelity with which visual signals are initially encoded. Subsequent stages of visual processing require synapses from bipolar cells to ganglion cells, but whether these synapses generate a significant amount of noise was unknown. To characterize noise generated by these synapses, we recorded excitatory postsynaptic currents from mammalian retinal ganglion cells and subjected them to a computational noise analysis. The release of transmitter quanta at bipolar cell synapses contributed substantially to the noise variance found in the ganglion cell, causing a significant loss of fidelity from bipolar cell array to postsynaptic ganglion cell. Virtually all the remaining noise variance originated in the presynaptic circuit. Circuit noise had a frequency content similar to noise shared by ganglion cells but a very different frequency content from noise from bipolar cell synapses, indicating that these synapses constitute a source of independent noise not shared by ganglion cells. These findings contribute a picture of daylight retinal circuits where noise from cones and noise generated by synaptic transmission of cone signals significantly limit visual fidelity. PMID:24297850

DSCAM Localization and Function at the Mouse Cone Synapse

PubMed Central

de Andrade, Gabriel Belem; Long, Samuel S.; Fleming, Harrison; Li, Wei; Fuerst, Peter G.

2014-01-01

The Down Syndrome Cell Adhesion Molecule (DSCAM) is required for regulation of cell number, soma spacing and cell type specific dendrite avoidance in many types of retinal ganglion and amacrine cells. In this study we assay the organization of cells making up the outer plexiform layer of the retina in the absence of Dscam. Some types of OFF bipolar cells, type 3b and type 4 bipolar cells, had defects in dendrite arborization in the Dscam mutant retina, while other cell types appeared similar to wild type. The cone synapses that these cells project their dendrites to were intact, as visualized by electron microscopy, and had a distribution and density that was not significantly different than wild type. The spacing of type 3b bipolar cell dendrites was further analyzed by Voronoi domain analysis, Density Recovery Profiling (DRP) analysis and Nearest Neighbor Analysis (NNA). Spacing was found to be significantly different when comparing wild type and mutant type 3b bipolar cell dendrites. Defects in arborization of these bipolar cells could not be attributed to the disorganization of inner plexiform layer cells that occurs in the Dscam mutant retina or an increase in cell number, as they arborized when Dscam was targeted in retinal ganglion cells only or in the bax null retina. Localization of DSCAM was assayed and the protein was localized near to cone synapses in mouse, macaque and ground squirrel retinas. DSCAM protein was detected in several types of bipolar cells, including type 3b and type 4 bipolar cells. PMID:24477985

Group III metabotropic glutamate receptors and exocytosed protons inhibit L-type calcium currents in cones but not in rods.

PubMed

Hosoi, Nobutake; Arai, Itaru; Tachibana, Masao

2005-04-20

Light responses of photoreceptors (rods and cones) are transmitted to the second-order neurons (bipolar cells and horizontal cells) via glutamatergic synapses located in the outer plexiform layer of the retina. Although it has been well established that postsynaptic group III metabotropic glutamate receptors (mGluRs) of ON bipolar cells contribute to generating the ON signal, presynaptic roles of group III mGluRs remain to be elucidated at this synaptic connection. We addressed this issue by applying the slice patch-clamp technique to the newt retina. OFF bipolar cells and horizontal cells generate a steady inward current in the dark and a transient inward current at light offset, both of which are mediated via postsynaptic non-NMDA receptors. A group III mGluR-specific agonist, L-2-amino-4-phosphonobutyric acid (L-AP-4), inhibited both the steady and off-transient inward currents but did not affect the glutamate-induced current in these postsynaptic neurons. L-AP-4 inhibited the presynaptic L-type calcium current (ICa) in cones by shifting the voltage dependence of activation to more positive membrane potentials. The inhibition of ICa was most prominent around the physiological range of cone membrane potentials. In contrast, L-AP-4 did not affect L-type ICa in rods. Paired recordings from photoreceptors and the synaptically connected second-order neurons confirmed that L-AP-4 inhibited both ICa and glutamate release in cones but not in rods. Furthermore, we found that exocytosed protons also inhibited ICa in cones but not in rods. Selective modulation of ICa in cones may help broaden the dynamic range of synaptic transfer by controlling the amount of transmitter release from cones.

Kainate receptors mediate signaling in both transient and sustained OFF bipolar cell pathways in mouse retina.

PubMed

Borghuis, Bart G; Looger, Loren L; Tomita, Susumu; Demb, Jonathan B

2014-04-30

A fundamental question in sensory neuroscience is how parallel processing is implemented at the level of molecular and circuit mechanisms. In the retina, it has been proposed that distinct OFF cone bipolar cell types generate fast/transient and slow/sustained pathways by the differential expression of AMPA- and kainate-type glutamate receptors, respectively. However, the functional significance of these receptors in the intact circuit during light stimulation remains unclear. Here, we measured glutamate release from mouse bipolar cells by two-photon imaging of a glutamate sensor (iGluSnFR) expressed on postsynaptic amacrine and ganglion cell dendrites. In both transient and sustained OFF layers, cone-driven glutamate release from bipolar cells was blocked by antagonists to kainate receptors but not AMPA receptors. Electrophysiological recordings from bipolar and ganglion cells confirmed the essential role of kainate receptors for signaling in both transient and sustained OFF pathways. Kainate receptors mediated responses to contrast modulation up to 20 Hz. Light-evoked responses in all mouse OFF bipolar pathways depend on kainate, not AMPA, receptors.

Bipolar cell gap junctions serve major signaling pathways in the human retina.

PubMed

Kántor, Orsolya; Varga, Alexandra; Nitschke, Roland; Naumann, Angela; Énzsöly, Anna; Lukáts, Ákos; Szabó, Arnold; Németh, János; Völgyi, Béla

2017-08-01

Connexin36 (Cx36) constituent gap junctions (GJ) throughout the brain connect neurons into functional syncytia. In the retina they underlie the transmission, averaging and correlation of signals prior conveying visual information to the brain. This is the first study that describes retinal bipolar cell (BC) GJs in the human inner retina, whose function is enigmatic even in the examined animal models. Furthermore, a number of unique features (e.g. fovea, trichromacy, midget system) necessitate a reexamination of the animal model results in the human retina. Well-preserved postmortem human samples of this study are allowed to identify Cx36 expressing BCs neurochemically. Results reveal that both rod and cone pathway interneurons display strong Cx36 expression. Rod BC inputs to AII amacrine cells (AC) appear in juxtaposition to AII GJs, thus suggesting a strategic AII cell targeting by rod BCs. Cone BCs serving midget, parasol or koniocellular signaling pathways display a wealth of Cx36 expression to form homologously coupled arrays. In addition, they also establish heterologous GJ contacts to serve an exchange of information between parallel signaling streams. Interestingly, a prominent Cx36 expression was exhibited by midget system BCs that appear to maintain intimate contacts with bistratified BCs serving other pathways. These findings suggest that BC GJs in parallel signaling streams serve both an intra- and inter-pathway exchange of signals in the human retina.

A spectral model for signal elements isolated from zebrafish photopic electroretinogram

PubMed Central

Nelson, Ralph; Singla, Nirmish

2009-01-01

The zebrafish photopic ERG sums isolatable elements. In each element red, blue, green and UV (r, g, b, u) cone signals combine in a way that reflects retinal organization. ERG responses to monochromatic stimuli of different wavelengths and irradiances were recorded on a white, rod suppressing background using superfused eyecups. Onset elements were isolated with glutamatergic blockers and response subtractions. CNQX blocked ionotropic (AMPA/kainate) glutamate receptors; L-AP4 or CPPG blocked metabotropic (mGluR6) glutamate receptors; TBOA blocked glutamate transporters; and L-Aspartate inactivated all glutamatergic mechanisms. Seven elements emerged: photopic PIII, the L-Aspartate-isolated cone response; b1, a CNQX-sensitive early b-wave element of inner retinal origin; PII, a photopic, CNQX-insensitive, composite b-wave element from ON bipolar cells; PIIm, an L-AP4/CPPG-sensitive, CNQX-insensitive metabotropic sub-element of PII; PIInm, an L-AP4/CPPG/CNQX-insensitive, non-metabotropic sub-element of PII; a1nm, a TBOA-sensitive, CNQX/L-AP4/CPPG-insensitive, non-metabotropic, post-photoreceptor a-wave element; and a2, a CNQX-sensitive a-wave element linked to OFF bipolar cells. The first five elements were fit with a spectral model that demonstrates independence of cone color pathways. From this Vmax and half-saturation values (k) for the contributing r- g- b- and u-cone signals were calculated. Two signal patterns emerged. For PIII or PIInm the Vmax order was Vr > Vg ≫ Vb ≈ Vu. For b1, PII, and PIIm the Vmax order was Vr ≈ Vb > Vg > Vu. In either pattern u-cone amplitude (Vu) was smallest, but u-cone sensitivity (ku362) was greatest, some 10-30 times greater than r-cone (kr570). The spectra of b1/PII/PIIm elements peaked near b-cone and u-cone absorbance maxima regardless of criteria, but the spectra of PIII/PIInm elements shifted from b- towards r-cone absorbance maxima as criterion levels increased. The greatest gains in Vmax relative to PIII occurred for the b- and u-cone signals in the b1/PII/PIIm b-wave elements. This suggests a high-gain, prolific metabotropic circuitry for b- and u-cone bipolar cells. PMID:19723365

Gsg1, Trnp1, and Tmem215 Mark Subpopulations of Bipolar Interneurons in the Mouse Retina

PubMed Central

Park, Ko Uoon; Randazzo, Grace; Jones, Kenneth L.; Brzezinski, Joseph A.

2017-01-01

Purpose How retinal bipolar cell interneurons are specified and assigned to specialized subtypes is only partially understood. In part, this is due to a lack of early pan- and subtype-specific bipolar cell markers. To discover these factors, we identified genes that were upregulated in Blimp1 (Prdm1) mutant retinas, which exhibit precocious bipolar cell development. Methods Postnatal day (P)2 retinas from Blimp1 conditional knock-out (CKO) mice and controls were processed for RNA sequencing. Genes that increased at least 45% and were statistically different between conditions were considered candidate bipolar-specific factors. Candidates were further evaluated by RT-PCR, in situ hybridization, and immunohistochemistry. Knock-in Tmem215-LacZ mice were used to better trace retinal expression. Results A comparison between Blimp1 CKO and control RNA-seq datasets revealed approximately 40 significantly upregulated genes. We characterized the expression of three genes that have no known function in the retina, Gsg1 (germ cell associated gene), Trnp1 (TMF-regulated nuclear protein), and Tmem215 (a predicted transmembrane protein). Germ cell associated gene appeared restricted to a small subset of cone bipolars while Trnp1 was seen in all ON type bipolar cells. Using Tmem215-LacZ heterozygous knock-in mice, we observed that β-galactosidase expression started early in bipolar cell development. In adults, Tmem215 was expressed by a subset of ON and OFF cone bipolar cells. Conclusions We have identified Gsg1, Tmem215, and Trnp1 as novel bipolar subtype-specific genes. The spatial and temporal pattern of their expression is consistent with a role in controlling bipolar subtype fate choice, differentiation, or physiology. PMID:28199486

Synaptology of physiologically identified ganglion cells in the cat retina: a comparison of retinal X- and Y-cells.

PubMed

Weber, A J; Stanford, L R

1994-05-15

It has long been known that a number of functionally different types of ganglion cells exist in the cat retina, and that each responds differently to visual stimulation. To determine whether the characteristic response properties of different retinal ganglion cell types might reflect differences in the number and distribution of their bipolar and amacrine cell inputs, we compared the percentages and distributions of the synaptic inputs from bipolar and amacrine cells to the entire dendritic arbors of physiologically characterized retinal X- and Y-cells. Sixty-two percent of the synaptic input to the Y-cell was from amacrine cell terminals, while the X-cells received approximately equal amounts of input from amacrine and bipolar cells. We found no significant difference in the distributions of bipolar or amacrine cell inputs to X- and Y-cells, or ON-center and OFF-center cells, either as a function of dendritic branch order or distance from the origin of the dendritic arbor. While, on the basis of these data, we cannot exclude the possibility that the difference in the proportion of bipolar and amacrine cell input contributes to the functional differences between X- and Y-cells, the magnitude of this difference, and the similarity in the distributions of the input from the two afferent cell types, suggest that mechanisms other than a simple predominance of input from amacrine or bipolar cells underlie the differences in their response properties. More likely, perhaps, is that the specific response features of X- and Y-cells originate in differences in the visual responses of the bipolar and amacrine cells that provide their input, or in the complex synaptic arrangements found among amacrine and bipolar cell terminals and the dendrites of specific types of retinal ganglion cells.

Requirement for Bhlhb5 in the specification of amacrine and cone bipolar subtypes in mouse retina

PubMed Central

Feng, Liang; Xie, Xiaoling; Joshi, Pushkar S.; Yang, Zhiyong; Shibasaki, Koji; Chow, Robert L.; Gan, Lin

2010-01-01

The mammalian retina comprises six major neuronal cell types and one glial type that are further classified into multiple subtypes based on their anatomical and functional differences. Nevertheless, how these subtypes arise remains largely unknown at the molecular level. Here, we demonstrate that the expression of Bhlhb5, a bHLH transcription factor of the Olig family, is tightly associated with the generation of selective GABAergic amacrine and Type 2 OFF-cone bipolar subtypes throughout retinogenesis. Targeted deletion of Bhlhb5 results in a significant reduction in the generation of these selective bipolar and amacrine subtypes. Furthermore, although a Bhlhb5-null mutation has no effect on the expression of bHLH-class retinogenic genes, Bhlhb5 expression overlaps with that of the pan-amacrine factor NeuroD and the expression of Bhlhb5 and NeuroD is negatively regulated by ganglion cell-competence factor Math5. Our results reveal that a bHLH transcription factor cascade is involved in regulating retinal cell differentiation and imply that Bhlhb5 functions downstream of retinogenic factors to specify bipolar and amacrine subtypes. PMID:17092954

RdgB2 is required for dim-light input into intrinsically photosensitive retinal ganglion cells

PubMed Central

Walker, Marquis T.; Rupp, Alan; Elsaesser, Rebecca; Güler, Ali D.; Sheng, Wenlong; Weng, Shijun; Berson, David M.; Hattar, Samer; Montell, Craig

2015-01-01

A subset of retinal ganglion cells is intrinsically photosensitive (ipRGCs) and contributes directly to the pupillary light reflex and circadian photoentrainment under bright-light conditions. ipRGCs are also indirectly activated by light through cellular circuits initiated in rods and cones. A mammalian homologue (RdgB2) of a phosphoinositide transfer/exchange protein that functions in Drosophila phototransduction is expressed in the retinal ganglion cell layer. This raised the possibility that RdgB2 might function in the intrinsic light response in ipRGCs, which depends on a cascade reminiscent of Drosophila phototransduction. Here we found that under high light intensities, RdgB2−/− mutant mice showed normal pupillary light responses and circadian photoentrainment. Consistent with this behavioral phenotype, the intrinsic light responses of ipRGCs in RdgB2−/− were indistinguishable from wild-type. In contrast, under low-light conditions, RdgB2−/− mutants displayed defects in both circadian photoentrainment and the pupillary light response. The RdgB2 protein was not expressed in ipRGCs but was in GABAergic amacrine cells, which provided inhibitory feedback onto bipolar cells. We propose that RdgB2 is required in a cellular circuit that transduces light input from rods to bipolar cells that are coupled to GABAergic amacrine cells and ultimately to ipRGCs, thereby enabling ipRGCs to respond to dim light. PMID:26269578

Bipolar Hemarthroplasty Using Cementless Conical Stem for Treatment of Dorr Type B and C Femoral Neck Fracture.

PubMed

Kang, Jeong Hoon; Lee, Sang Hong; Jung, Sung

2015-12-01

The current study aims to evaluate the clinical and the radiological outcome of bipolar hemiarthroplasty using cementless cone stem to treat osteoporotic femoral neck fracture and compare the results according to the proximal femur geometry. Seventy-five hips (75 patients) that underwent bipolar hemiarthroplasty with cementless cone stem between September 2006 and December 2011 were analyzed. The minimum follow-up period was 3 years. Thirty-three hips were classified as type B and 41 as type C. The clinical outcome was assessed using Harris hip score and the walking ability score. Radiographic evaluation was performed to evaluate the stability of the prosthesis. At the most recent follow up, the mean Harris hip score was 86 (range, 70-92) and 65% recovered to preoperative ambulatory status. In the radiographic exam, stable stem fixation was achieved in all cases. For the complications, eight hips developed deep vein thrombosis while three hips showed heterotopic ossification. Dislocation and delayed deep infection occurred in one hip resepectively. There were no significance differences in Harris hip score and walking ability score when the type B group was compare with the type C. Bipolar hemiarthroplasty with cementless cone stem showed an excellent early outcome both clinically and radiographically regardless of the shape of the proximal femur. We believe this prosthesis can provide early stability to the Dorr type B and C femur and is an effective treatment for treating osteoporotic femoral neck fracture.

Two R7 RGS proteins shape retinal bipolar cell signaling

PubMed Central

Mojumder, Deb Kumar; Qian, Yan; Wensel, Theodore G.

2009-01-01

RGS7, RGS11, and their binding partner Gβ5 are localized to the dendritic tips of retinal ON bipolar cells (ON-BPC), where mGluR6 responds to glutamate released from photoreceptor terminals by activation of the RGS7/RGS11 substrate, Gαo. To determine their functions in retinal signaling, we investigated cell-specific expression patterns of RGS7 and RGS11 by immunostaining, and measured light responses by electroretinography (ERG) in mice with targeted disruptions of the genes encoding them. RGS7 staining is present in dendritic tips of all rod ON-BPC, but missing in those for subsets of cone ON-BPC, whereas the converse was true for RGS11 staining. Genetic disruption of either RGS7 or RGS11 produced delays in the ON-BPC-derived electroretinogram b-wave, but no changes in the photoreceptor-derived a-wave. Homozygous RGS7 mutant mice had delays in rod-driven b-waves, whereas, RGS11 mutant mice had delays in rod-driven, and especially in cone-driven b-waves. The b-wave delays were further enhanced in mice homozygous for both RGS7 and RGS11 gene disruptions. Thus, RGS7 and RGS11 act in parallel to regulate the kinetics of ON bipolar cell responses, with differential impacts on the rod and cone pathways. PMID:19535587

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

PubMed

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.

Nano-cone resistive memory for ultralow power operation.

PubMed

Kim, Sungjun; Jung, Sunghun; Kim, Min-Hwi; Kim, Tae-Hyeon; Bang, Suhyun; Cho, Seongjae; Park, Byung-Gook

2017-03-24

SiN x -based nano-structure resistive memory is fabricated by fully silicon CMOS compatible process integration including particularly designed anisotropic etching for the construction of a nano-cone silicon bottom electrode (BE). Bipolar resistive switching characteristics have significantly reduced switching current and voltage and are demonstrated in a nano-cone BE structure, as compared with those in a flat BE one. We have verified by systematic device simulations that the main cause of reduction in the performance parameters is the high electric field being more effectively concentrated at the tip of the cone-shaped BE. The greatly improved nonlinearity of the nano-cone resistive memory cell will be beneficial in the ultra-high-density crossbar array.

Paired-Pulse Depression at Photoreceptor Synapses

PubMed Central

Rabl, Katalin; Cadetti, Lucia; Thoreson, Wallace B.

2011-01-01

Synaptic depression produced by repetitive stimulation is likely to be particularly important in shaping responses of second-order retinal neurons at the tonically active photoreceptor synapse. We analyzed the time course and mechanisms of synaptic depression at rod and cone synapses using paired-pulse protocols involving two complementary measurements of exocytosis: (1) paired whole-cell recordings of the postsynaptic current (PSC) in second-order retinal neurons and (2) capacitance measurements of vesicular membrane fusion in rods and cones. PSCs in ON bipolar, OFF bipolar, and horizontal cells evoked by stimulation of either rods or cones recovered from paired-pulse depression (PPD) at rates similar to the recovery of exocytotic capacitance changes in rods and cones. Correlation between presynaptic and postsynaptic measures of recovery from PPD suggests that 80 –90% of the depression at these synapses is presynaptic in origin. Consistent with a predominantly presynaptic mechanism, inhibiting desensitization of postsynaptic glutamate receptors had little effect on PPD. The depression of exocytotic capacitance changes exceeded depression of the presynaptic calcium current, suggesting that it is primarily caused by a depletion of synaptic vesicles. In support of this idea, limiting Ca2+ influx by using weaker depolarizing stimuli promoted faster recovery from PPD. Although cones exhibit much faster exocytotic kinetics than rods, exocytotic capacitance changes recovered from PPD at similar rates in both cell types. Thus, depression of release is not likely to contribute to differences in the kinetics of transmission from rods and cones. PMID:16510733

Imer-product array processor for retrieval of stored images represented by bipolar binary (+1,-1) pixels using partial input trinary pixels represented by (+1,-1)

NASA Technical Reports Server (NTRS)

Liu, Hua-Kuang (Inventor); Awwal, Abdul A. S. (Inventor); Karim, Mohammad A. (Inventor)

1993-01-01

An inner-product array processor is provided with thresholding of the inner product during each iteration to make more significant the inner product employed in estimating a vector to be used as the input vector for the next iteration. While stored vectors and estimated vectors are represented in bipolar binary (1,-1), only those elements of an initial partial input vector that are believed to be common with those of a stored vector are represented in bipolar binary; the remaining elements of a partial input vector are set to 0. This mode of representation, in which the known elements of a partial input vector are in bipolar binary form and the remaining elements are set equal to 0, is referred to as trinary representation. The initial inner products corresponding to the partial input vector will then be equal to the number of known elements. Inner-product thresholding is applied to accelerate convergence and to avoid convergence to a negative input product.

Early changes in synaptic connectivity following progressive photoreceptor degeneration in RCS rats.

PubMed

Cuenca, Nicolás; Pinilla, Isabel; Sauvé, Yves; Lund, Raymond

2005-09-01

The Royal College of Surgeons (RCS) rat has a retinal pigment epithelial cell defect that causes progressive loss of photoreceptors. Although it is extensively used in retinal degeneration and repair studies, how photoreceptor degeneration affects retinal circuitry has not been fully explored. This study examined the changes in synaptic connectivity between photoreceptors and their target cells using immunocytochemistry and correlated these changes with retinal function using the electroretinogram (ERG). Immunostaining with bassoon and synaptophysin (as presynaptic markers) and metabotropic glutamate receptor (mGluR6, a postsynaptic marker for ON-bipolar dendrites) was already impaired at postnatal day (P) 21 and progressively lost with infrequent pairing of presynaptic and postsynaptic elements at P60. By P90 to P120, staining became increasingly patchy and was eventually restricted to sparsely and irregularly distributed foci in which the normal pairing of presynaptic and postsynaptic markers was lost. ERG results showed that mixed scotopic a-waves and b-waves were already reduced by P21 but not oscillatory potentials. While cone-driven responses (photopic b-wave) reached normal levels at P30, they were impaired by P60 but could still be recorded at P120, although with reduced amplitude; rod responses never reached normal amplitudes. Thus, only cone-driven activity attained normal levels, but declined rapidly thereafter. In conclusion, the synaptic markers associated with photoreceptors and processes of bipolar and horizontal cells show abnormalities prior to significant photoreceptor loss. These changes are paralleled with the deterioration of specific aspects of ERG responsiveness with age. Besides providing information on the effects of photoreceptor dysfunction and loss on connection patterns in the retina, the work addresses the more general issue of how disorder of input neurons affects downstream circuitry.

Differential cellular and subcellular distribution of glutamate transporters in the cat retina.

PubMed

Fyk-Kolodziej, Bozena; Qin, Pu; Dzhagaryan, Arturik; Pourcho, Roberta G

2004-01-01

Retrieval of glutamate from extracellular sites in the retina involves at least five excitatory amino acid transporters. Immunocytochemical analysis of the cat retina indicates that each of these transporters exhibits a selective distribution which may reflect its specific function. The uptake of glutamate into Muller cells or astrocytes appears to depend upon GLAST and EAAT4, respectively. Staining for EAAT4 was also seen in the pigment epithelium. The remaining transporters are neuronal with GLT-1alpha localized to a number of cone bipolar, amacrine, and ganglion cells and GLT-1v in cone photoreceptors and several populations of bipolar cells. The EAAC1 transporter was found in horizontal, amacrine, and ganglion cells. Staining for EAAT5 was seen in the axon terminals of both rod and cone photoreceptors as well as in numerous amacrine and ganglion cells. Although some of the glutamate transporter molecules are positioned for presynaptic or postsynaptic uptake at glutamatergic synapses, others with localizations more distant from such contacts may serve in modulatory roles or provide protection against excitoxic or oxidative damage.

Physiological and morphological characterization of ganglion cells in the salamander retina

PubMed Central

Wang, Jing; Jacoby, Roy; Wu, Samuel M.

2016-01-01

Retinal ganglion cells (RGCs) integrate visual information from the retina and transmit collective signals to the brain. A systematic investigation of functional and morphological characteristics of various types of RGCs is important to comprehensively understand how the visual system encodes and transmits information via various RGC pathways. This study evaluated both physiological and morphological properties of 67 RGCs in dark-adapted flat-mounted salamander retina by examining light-evoked cation and chloride current responses via voltage-clamp recordings and visualizing morphology by Lucifer yellow fluorescence with a confocal microscope. Six groups of RGCs were described: asymmetrical ON–OFF RGCs, symmetrical ON RGCs, OFF RGCs, and narrow-, medium- and wide-field ON–OFF RGCs. Dendritic field diameters of RGCs ranged 102–490 µm: narrow field (<200 µm, 31% of RGCs), medium field (200–300 µm, 45%) and wide field (>300 µm, 24%). Dendritic ramification patterns of RGCs agree with the sub-lamina A/B rule. 34% of RGCs were monostratified, 24% bistratified and 42% diffusely stratified. 70% of ON RGCs and OFF RGCs were monostratified. Wide-field RGCs were diffusely stratified. 82% of RGCs generated light-evoked ON–OFF responses, while 11% generated ON responses and 7% OFF responses. Response sensitivity analysis suggested that some RGCs obtained separated rod/cone bipolar cell inputs whereas others obtained mixed bipolar cell inputs. 25% of neurons in the RGC layer were displaced amacrine cells. Although more types may be defined by more refined classification criteria, this report is to incorporate more physiological properties into RGC classification. PMID:26731645

Expression of the vesicular glutamate transporter vGluT2 in a subset of cones of the mouse retina.

PubMed

Wässle, Heinz; Regus-Leidig, Hanna; Haverkamp, Silke

2006-06-01

Cone photoreceptors have a continuous release of glutamate that is modulated by light. Vesicular glutamate transporters (vGluT) play an essential role for sustaining this release by loading synaptic vesicles in the cone synapse, the so-called cone pedicle. In the present study mouse retinas were immunostained for vGluT1 and vGluT2. vGluT1 was localized to all cone pedicles and rod spherules, whereas vGluT2 was found in only 10% of the cone pedicles. The vGluT2-expressing cones were characterized in more detail. They are distributed in a regular array, suggesting they are a distinct type. Their proportion does not differ between dorsal (L-cone-dominated) and ventral (S-cone-dominated) retina, and they are not the genuine blue cones of the mouse retina. During development, vGluT1 and vGluT2 expression in cones starts at around P0 and right from the beginning vGluT2 is only expressed in a subset of cones. Bipolar cells contact the vGluT2-expressing cones and other cones nonselectively. The possible functional role of vGluT2 expression in a small fraction of cones is discussed.

Progress toward the maintenance and repair of degenerating retinal circuitry.

PubMed

Vugler, Anthony A

2010-01-01

Retinal diseases such as age-related macular degeneration and retinitis pigmentosa remain major causes of severe vision loss in humans. Clinical trials for treatment of retinal degenerations are underway and advancements in our understanding of retinal biology in health/disease have implications for novel therapies. A review of retinal biology is used to inform a discussion of current strategies to maintain/repair neural circuitry in age-related macular degeneration, retinitis pigmentosa, and Type 2 Leber congenital amaurosis. In age-related macular degeneration/retinitis pigmentosa, a progressive loss of rods/cones results in corruption of bipolar cell circuitry, although retinal output neurons/photoreceptive melanopsin cells survive. Visual function can be stabilized/enhanced after treatment in age-related macular degeneration, but in advanced degenerations, reorganization of retinal circuitry may preclude attempts to restore cone function. In Type 2 Leber congenital amaurosis, useful vision can be restored by gene therapy where central cones survive. Remarkable progress has been made in restoring vision to rodents using light-responsive ion channels inserted into bipolar cells/retinal ganglion cells. Advances in genetic, cellular, and prosthetic therapies show varying degrees of promise for treating retinal degenerations. While functional benefits can be obtained after early therapeutic interventions, efforts should be made to minimize circuitry changes as soon as possible after rod/cone loss. Advances in retinal anatomy/physiology and genetic technologies should allow refinement of future reparative strategies.

Progression of neuronal and synaptic remodeling in the rd10 mouse model of retinitis pigmentosa.

PubMed

Phillips, M Joseph; Otteson, Deborah C; Sherry, David M

2010-06-01

The Pde6b(rd10) (rd10) mouse has a moderate rate of photoreceptor degeneration and serves as a valuable model for human autosomal recessive retinitis pigmentosa (RP). We evaluated the progression of neuronal remodeling of second- and third-order retinal cells and their synaptic terminals in retinas from Pde6b(rd10) (rd10) mice at varying stages of degeneration ranging from postnatal day 30 (P30) to postnatal month 9.5 (PNM9.5) using immunolabeling for well-known cell- and synapse-specific markers. Following photoreceptor loss, changes occurred progressively from outer to inner retina. Horizontal cells and rod and cone bipolar cells underwent morphological remodeling that included loss of dendrites, cell body migration, and the sprouting of ectopic processes. Gliosis, characterized by translocation of Müller cell bodies to the outer retina and thickening of their processes, was evident by P30 and became more pronounced as degeneration progressed. Following rod degeneration, continued expression of VGluT1 in the outer retina was associated with survival and expression of synaptic proteins by nearby second-order neurons. Rod bipolar cell terminals showed a progressive reduction in size and ectopic bipolar cell processes extended into the inner nuclear layer and ganglion cell layer by PNM3.5. Putative ectopic conventional synapses, likely arising from amacrine cells, were present in the inner nuclear layer by PNM9.5. Despite these changes, the laminar organization of bipolar and amacrine cells and the ON-OFF organization in the inner plexiform layer was largely preserved. Surviving cone and bipolar cell terminals continued to express the appropriate cell-specific presynaptic proteins needed for synaptic function up to PNM9.5. (c) 2010 Wiley-Liss, Inc.

Progression of Neuronal and Synaptic Remodeling in the rd10 Mouse Model of Retinitis Pigmentosa

PubMed Central

Phillips, M. Joseph; Otteson, Deborah C.; Sherry, David M.

2010-01-01

The Pde6brd10 (rd10) mouse has a moderate rate of photoreceptor degeneration and serves as a valuable model for human autosomal recessive retinitis pigmentosa (RP). We evaluated the progression of neuronal remodeling of second- and third-order retinal cells and their synaptic terminals in retinas from Pde6brd10 (rd10) mice at varying stages of degeneration ranging from postnatal day 30 (P30) to postnatal month 9.5 (PNM9.5) using immunolabeling for well known cell- and synapse-specific markers. Following photoreceptor loss, changes occurred progressively from outer to inner retina. Horizontal cells and rod and cone bipolar cells underwent morphological remodeling that included loss of dendrites, cell body migration, and the sprouting of ectopic processes. Gliosis, characterized by translocation of Müller cell bodies to the outer retina and thickening of their processes, was evident by P30 and became more pronounced as degeneration progressed. Following rod degeneration, continued expression of VGluT1 in the outer retina was associated with survival and expression of synaptic proteins by nearby second-order neurons. Rod bipolar cell terminals showed a progressive reduction in size and ectopic bipolar cell processes extended into the inner nuclear layer and ganglion cell layer by PNM3.5. Putative ectopic conventional synapses, likely arising from amacrine cells, were present in the inner nuclear layer by PNM9.5. Despite these changes, the laminar organization of bipolar and amacrine cells and the ON-OFF organization in the inner plexiform layer was largely preserved. Surviving cone and bipolar cell terminals continued to express the appropriate cell-specific presynaptic proteins needed for synaptic function up to PNM9.5. PMID:20394059

RdgB2 is required for dim-light input into intrinsically photosensitive retinal ganglion cells.

PubMed

Walker, Marquis T; Rupp, Alan; Elsaesser, Rebecca; Güler, Ali D; Sheng, Wenlong; Weng, Shijun; Berson, David M; Hattar, Samer; Montell, Craig

2015-10-15

A subset of retinal ganglion cells is intrinsically photosensitive (ipRGCs) and contributes directly to the pupillary light reflex and circadian photoentrainment under bright-light conditions. ipRGCs are also indirectly activated by light through cellular circuits initiated in rods and cones. A mammalian homologue (RdgB2) of a phosphoinositide transfer/exchange protein that functions in Drosophila phototransduction is expressed in the retinal ganglion cell layer. This raised the possibility that RdgB2 might function in the intrinsic light response in ipRGCs, which depends on a cascade reminiscent of Drosophila phototransduction. Here we found that under high light intensities, RdgB2(-/-) mutant mice showed normal pupillary light responses and circadian photoentrainment. Consistent with this behavioral phenotype, the intrinsic light responses of ipRGCs in RdgB2(-/-) were indistinguishable from wild-type. In contrast, under low-light conditions, RdgB2(-/-) mutants displayed defects in both circadian photoentrainment and the pupillary light response. The RdgB2 protein was not expressed in ipRGCs but was in GABAergic amacrine cells, which provided inhibitory feedback onto bipolar cells. We propose that RdgB2 is required in a cellular circuit that transduces light input from rods to bipolar cells that are coupled to GABAergic amacrine cells and ultimately to ipRGCs, thereby enabling ipRGCs to respond to dim light. © 2015 Walker et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Homeostatic plasticity shapes cell-type-specific wiring in the retina

PubMed Central

Tien, Nai-Wen; Soto, Florentina; Kerschensteiner, Daniel

2017-01-01

SUMMARY Convergent input from different presynaptic partners shapes the responses of postsynaptic neurons. Whether developing postsynaptic neurons establish connections with each presynaptic partner independently, or balance inputs to attain specific responses is unclear. Retinal ganglion cells (RGCs) receive convergent input from bipolar cell types with different contrast responses and temporal tuning. Here, using optogenetic activation and pharmacogenetic silencing, we found that type 6 bipolar cells (B6) dominate excitatory input to ONα-RGCs. We generated mice in which B6 cells were selectively removed from developing circuits (B6-DTA). In B6-DTA mice, ONα-RGCs adjusted connectivity with other bipolar cells in a cell-type-specific manner. They recruited new partners, increased synapses with some existing partners, and maintained constant input from others. Patch clamp recordings revealed that anatomical rewiring precisely preserved contrast- and temporal frequency response functions of ONα-RGCs, indicating that homeostatic plasticity shapes cell-type-specific wiring in the developing retina to stabilize visual information sent to the brain. PMID:28457596

The pattern of expression of guanine nucleotide-binding protein β3 (GNB3) in the retina is conserved across vertebrate species

PubMed Central

Ritchey, Eric R.; Bongini, Rachel E.; Code, Kimberly A.; Zelinka, Christopher; Petersen-Jones, Simon; Fischer, Andy J.

2010-01-01

Guanine nucleotide-binding protein β3 (GNB3) is an isoform of the β subunit of the heterotrimeric G protein second messenger complex that is commonly associated with transmembrane receptors. The presence of GNB3 in photoreceptors, and possibly bipolar cells, has been confirmed in murine, bovine and primate retinas (Lee et al., 1992, Peng et al., 1992, Huang et al., 2003). Studies have indicated that a mutation in the GNB3 gene causes progressive retinopathy and globe enlargement (RGE) in chickens. The goals of this study were to 1) examine the expression pattern of GNB3 in wild-type and RGE mutant chickens, 2) characterize the types of bipolar cells that express GNB3 and 3) examine whether the expression of GNB3 in the retina is conserved across vertebrate species. We find that chickens homozygous for the RGE allele completely lack GNB3 protein. We find that the pattern of expression of GNB3 in the retina is highly conserved across vertebrate species, including teleost fish (Carassius auratus), frogs (Xenopus laevis), chickens (Gallus domesticus), mice (Mus musculata), guinea pigs (Cavia porcellus), dogs (Canis familiaris) and non-human primates (Macaca fasicularis). Regardless of the species, we find that GNB3 is expressed by Islet1-positive cone ON-bipolar cells and by cone photoreceptors. In some vertebrates, GNB3-immunoreactivity was observed in both rod and cone photoreceptors. A protein-protein alignment of GNB3 across different vertebrates, from fish to humans, indicates a high degree (>92%) of sequence conservation. Given that analogous types of retinal neurons express GNB3 in different species, we propose that the functions and the mechanisms that regulate the expression of GNB3 are highly conserved. PMID:20538044

Spatial structure of cone inputs to receptive fields in primate lateral geniculate nucleus

NASA Astrophysics Data System (ADS)

Reid, R. Clay; Shapley, Robert M.

1992-04-01

HUMAN colour vision depends on three classes of cone photoreceptors, those sensitive to short (S), medium (M) or long (L) wavelengths, and on how signals from these cones are combined by neurons in the retina and brain. Macaque monkey colour vision is similar to human, and the receptive fields of macaque visual neurons have been used as an animal model of human colour processing1. P retinal ganglion cells and parvocellular neurons are colour-selective neurons in macaque retina and lateral geniculate nucleus. Interactions between cone signals feeding into these neurons are still unclear. On the basis of experimental results with chromatic adaptation, excitatory and inhibitory inputs from L and M cones onto P cells (and parvocellular neurons) were thought to be quite specific2,3 (Fig. la). But these experiments with spatially diffuse adaptation did not rule out the 'mixed-surround' hypothesis: that there might be one cone-specific mechanism, the receptive field centre, and a surround mechanism connected to all cone types indiscriminately (Fig. le). Recent work has tended to support the mixed-surround hypothesis4-8. We report here the development of new stimuli to measure spatial maps of the linear L-, M- and S-cone inputs to test the hypothesis definitively. Our measurements contradict the mixed-surround hypothesis and imply cone specificity in both centre and surround.

Quantifying the effect of light activated outer and inner retinal inhibitory pathways on glutamate release from mixed bipolar cells.

PubMed

Lipin, Mikhail Y; Vigh, Jozsef

2018-05-01

Inhibition mediated by horizontal and amacrine cells in the outer and inner retina, respectively, are fundamental components of visual processing. Here, our purpose was to determine how these different inhibitory processes affect glutamate release from ON bipolar cells when the retina is stimulated with full-field light of various intensities. Light-evoked membrane potential changes (ΔV m ) were recorded directly from axon terminals of intact bipolar cells receiving mixed rod and cone inputs (Mbs) in slices of dark-adapted goldfish retina. Inner and outer retinal inhibition to Mbs was blocked with bath applied picrotoxin (PTX) and NBQX, respectively. Then, control and pharmacologically modified light responses were injected into axotomized Mb terminals as command potentials to induce voltage-gated Ca 2+ influx (Q Ca ) and consequent glutamate release. Stimulus-evoked glutamate release was quantified by the increase in membrane capacitance (ΔC m ). Increasing depolarization of Mb terminals upon removal of inner and outer retinal inhibition enhanced the ΔV m /Q Ca ratio equally at a given light intensity and inhibition did not alter the overall relation between Q Ca and ΔC m . However, relative to control, light responses recorded in the presence of PTX and PTX + NBQX increased ΔC m unevenly across different stimulus intensities: at dim stimulus intensities predominantly the inner retinal GABAergic inhibition controlled release from Mbs, whereas the inner and outer retinal inhibition affected release equally in response to bright stimuli. Furthermore, our results suggest that non-linear relationship between Q Ca and glutamate release can influence the efficacy of inner and outer retinal inhibitory pathways to mediate Mb output at different light intensities. © 2018 Wiley Periodicals, Inc.

Noise masking of S-cone increments and decrements.

PubMed

Wang, Quanhong; Richters, David P; Eskew, Rhea T

2014-11-12

S-cone increment and decrement detection thresholds were measured in the presence of bipolar, dynamic noise masks. Noise chromaticities were the L-, M-, and S-cone directions, as well as L-M, L+M, and achromatic (L+M+S) directions. Noise contrast power was varied to measure threshold Energy versus Noise (EvN) functions. S+ and S- thresholds were similarly, and weakly, raised by achromatic noise. However, S+ thresholds were much more elevated by S, L+M, L-M, L- and M-cone noises than were S- thresholds, even though the noises consisted of two symmetric chromatic polarities of equal contrast power. A linear cone combination model accounts for the overall pattern of masking of a single test polarity well. L and M cones have opposite signs in their effects upon raising S+ and S- thresholds. The results strongly indicate that the psychophysical mechanisms responsible for S+ and S- detection, presumably based on S-ON and S-OFF pathways, are distinct, unipolar mechanisms, and that they have different spatiotemporal sampling characteristics, or contrast gains, or both. © 2014 ARVO.

A five-primary photostimulator suitable for studying intrinsically photosensitive retinal ganglion cell functions in humans

PubMed Central

Cao, Dingcai; Nicandro, Nathaniel; Barrionuevo, Pablo A.

2015-01-01

Intrinsically photosensitive retinal ganglion cells (ipRGCs) can respond to light directly through self-contained photopigment, melanopsin. IpRGCs also receive synaptic inputs from rods and cones. Thus, studying ipRGC functions requires a novel photostimulating method that can account for all of the photoreceptor inputs. Here, we introduced an inexpensive LED-based five-primary photostimulator that can control the excitations of rods, S-, M-, L-cones, and melanopsin-containing ipRGCs in humans at constant background photoreceptor excitation levels, a critical requirement for studying the adaptation behavior of ipRGCs with rod, cone, or melanopsin input. We described the theory and technical aspects (including optics, electronics, software, and calibration) of the five-primary photostimulator. Then we presented two preliminary studies using the photostimulator we have implemented to measure melanopsin-mediated pupil responses and temporal contrast sensitivity function (TCSF). The results showed that the S-cone input to pupil responses was antagonistic to the L-, M- or melanopsin inputs, consistent with an S-OFF and (L + M)-ON response property of primate ipRGCs (Dacey et al., 2005). In addition, the melanopsin-mediated TCSF had a distinctive pattern compared with L + M or S-cone mediated TCSF. Other than controlling individual photoreceptor excitation independently, the five-primary photostimulator has the flexibility in presenting stimuli modulating any combination of photoreceptor excitations, which allows researchers to study the mechanisms by which ipRGCs combine various photoreceptor inputs. PMID:25624466

The role of retinal bipolar cell in early vision: an implication with analogue networks and regularization theory.

PubMed

Yagi, T; Ohshima, S; Funahashi, Y

1997-09-01

A linear analogue network model is proposed to describe the neuronal circuit of the outer retina consisting of cones, horizontal cells, and bipolar cells. The model reflects previous physiological findings on the spatial response properties of these neurons to dim illumination and is expressed by physiological mechanisms, i.e., membrane conductances, gap-junctional conductances, and strengths of chemical synaptic interactions. Using the model, we characterized the spatial filtering properties of the bipolar cell receptive field with the standard regularization theory, in which the early vision problems are attributed to minimization of a cost function. The cost function accompanying the present characterization is derived from the linear analogue network model, and one can gain intuitive insights on how physiological mechanisms contribute to the spatial filtering properties of the bipolar cell receptive field. We also elucidated a quantitative relation between the Laplacian of Gaussian operator and the bipolar cell receptive field. From the computational point of view, the dopaminergic modulation of the gap-junctional conductance between horizontal cells is inferred to be a suitable neural adaptation mechanism for transition between photopic and mesopic vision.

Expression of the LIM-Homeodomain Protein Isl1 in the Developing and Mature Mouse Retina

PubMed Central

Elshatory, Yasser; Deng, Min; Xie, Xiaoling; Gan, Lin

2010-01-01

The mammalian retina is comprised of six major neuronal cell types and is subdivided into more morphological and physiological subtypes. The transcriptional machinery underlying these subtype fate choices is largely unknown. The LIM-homeodomain protein, Isl1, plays an essential role in central nervous system (CNS) differentiation but its relationship to retinal neurogenesis remains unknown. We report here its dynamic spatiotemporal expression in the mouse retina. Among bipolar interneurons, Isl1 expression commences at postnatal day (P)5 and is later restricted to ON-bipolar cells. The intensity of Isl1 expression is found to segregate the pool of ON-bipolar cells into rod and ON-cone bipolar cells with higher expression in rod bipolar cells. As bipolar cell development proceeds from P5–10 the colocalization of Isl1 and the pan-bipolar cell marker Chx10 reveals the organization of ON-center bipolar cell nuclei to the upper portion of the inner nuclear layer. Further, whereas Isl1 is predominantly a ganglion cell marker prior to embryonic day (E)15.5, at E15.5 and later its expression in nonganglion cells expands. We demonstrate that these Isl1-positive, nonganglion cells acquire the expression of amacrine cell markers embryonically, likely representing nascent cholinergic amacrine cells. Taken together, Isl1 is expressed during the maturation of and is later maintained in retinal ganglion cells and subtypes of amacrine and bipolar cells where it may function in the maintenance of these cells into adulthood. J. Comp. Neurol. 503: 182–197, 2007. PMID:17480014

Ensemble Forecasting of Coronal Mass Ejections Using the WSA-ENLIL with CONED Model

NASA Technical Reports Server (NTRS)

Emmons, D.; Acebal, A.; Pulkkinen, A.; Taktakishvili, A.; MacNeice, P.; Odstricil, D.

2013-01-01

The combination of the Wang-Sheeley-Arge (WSA) coronal model, ENLIL heliospherical model version 2.7, and CONED Model version 1.3 (WSA-ENLIL with CONED Model) was employed to form ensemble forecasts for 15 halo coronal mass ejections (halo CMEs). The input parameter distributions were formed from 100 sets of CME cone parameters derived from the CONED Model. The CONED Model used image processing along with the bootstrap approach to automatically calculate cone parameter distributions from SOHO/LASCO imagery based on techniques described by Pulkkinen et al. (2010). The input parameter distributions were used as input to WSA-ENLIL to calculate the temporal evolution of the CMEs, which were analyzed to determine the propagation times to the L1 Lagrangian point and the maximum Kp indices due to the impact of the CMEs on the Earth's magnetosphere. The Newell et al. (2007) Kp index formula was employed to calculate the maximum Kp indices based on the predicted solar wind parameters near Earth assuming two magnetic field orientations: a completely southward magnetic field and a uniformly distributed clock-angle in the Newell et al. (2007) Kp index formula. The forecasts for 5 of the 15 events had accuracy such that the actual propagation time was within the ensemble average plus or minus one standard deviation. Using the completely southward magnetic field assumption, 10 of the 15 events contained the actual maximum Kp index within the range of the ensemble forecast, compared to 9 of the 15 events when using a uniformly distributed clock angle.

High sensitivity rod photoreceptor input to the blue-yellow color opponent pathway in macaque retina

PubMed Central

Field, Greg D.; Greschner, Martin; Gauthier, Jeffrey L.; Rangel, Carolina; Shlens, Jonathon; Sher, Alexander; Marshak, David W.; Litke, Alan M.; Chichilnisky, E.J.

2009-01-01

Small bistratified cells (SBCs) in the primate retina carry a major blue-yellow opponent signal to the brain. Here we show that SBCs also carry signals from rod photoreceptors, with the same sign as S cone input. SBCs exhibited robust responses under low scotopic conditions (<0.01 P*/rod/s). Physiological and anatomical experiments indicated that this rod input arose from the AII amacrine cell mediated rod pathway. Rod and cone signals were both present in SBCs at mesopic light levels. We discuss three implications of these findings. First, more retinal circuits than previously thought may multiplex rod and cone signals, efficiently exploiting the limited number of optic nerve fibers. Second, signals from AII amacrine cells may diverge to most or all of the <20 RGC types in the peripheral primate retina. Third, rod input to SBCs may be the substrate for behavioral biases toward perception of blue at mesopic light levels. PMID:19668201

Vesicle Pool Size at the Salamander Cone Ribbon Synapse

PubMed Central

Bartoletti, Theodore M.; Babai, Norbert

2010-01-01

Cone light responses are transmitted to postsynaptic neurons by changes in the rate of synaptic vesicle release. Vesicle pool size at the cone synapse constrains the amount of release and can thus shape contrast detection. We measured the number of vesicles in the rapidly releasable and reserve pools at cone ribbon synapses by performing simultaneous whole cell recording from cones and horizontal or off bipolar cells in the salamander retinal slice preparation. We found that properties of spontaneously occurring miniature excitatory postsynaptic currents (mEPSCs) are representative of mEPSCs evoked by depolarizing presynaptic stimulation. Strong, brief depolarization of the cone stimulated release of the entire rapidly releasable pool (RRP) of vesicles. Comparing charge transfer of the EPSC with mEPSC charge transfer, we determined that the fast component of the EPSC reflects release of ∼40 vesicles. Comparing EPSCs with simultaneous presynaptic capacitance measurements, we found that horizontal cell EPSCs constitute 14% of the total number of vesicles released from a cone terminal. Using a fluorescent ribeye-binding peptide, we counted ∼13 ribbons per cone. Together, these results suggest each cone contacts a single horizontal cell at ∼2 ribbons. The size of discrete components in the EPSC amplitude histogram also suggested ∼2 ribbon contacts per cell pair. We therefore conclude there are ∼20 vesicles per ribbon in the RRP, similar to the number of vesicles contacting the plasma membrane at the ribbon base. EPSCs evoked by lengthy depolarization suggest a reserve pool of ∼90 vesicles per ribbon, similar to the number of additional docking sites further up the ribbon. PMID:19923246

Comparison of interplanetary CME arrival times and solar wind parameters based on the WSA-ENLIL model with three cone types and observations

NASA Astrophysics Data System (ADS)

Jang, Soojeong; Moon, Y.-J.; Lee, Jae-Ok; Na, Hyeonock

2014-09-01

We have made a comparison between coronal mass ejection (CME)-associated shock propagations based on the Wang-Sheeley-Arge (WSA)-ENLIL model using three cone types and in situ observations. For this we use 28 full-halo CMEs, whose cone parameters are determined and their corresponding interplanetary shocks were observed at the Earth, from 2001 to 2002. We consider three different cone types (an asymmetric cone model, an ice cream cone model, and an elliptical cone model) to determine 3-D CME cone parameters (radial velocity, angular width, and source location), which are the input values of the WSA-ENLIL model. The mean absolute error of the CME-associated shock travel times for the WSA-ENLIL model using the ice-cream cone model is 9.9 h, which is about 1 h smaller than those of the other models. We compare the peak values and profiles of solar wind parameters (speed and density) with in situ observations. We find that the root-mean-square errors of solar wind peak speed and density for the ice cream and asymmetric cone model are about 190 km/s and 24/cm3, respectively. We estimate the cross correlations between the models and observations within the time lag of ± 2 days from the shock travel time. The correlation coefficients between the solar wind speeds from the WSA-ENLIL model using three cone types and in situ observations are approximately 0.7, which is larger than those of solar wind density (cc ˜0.6). Our preliminary investigations show that the ice cream cone model seems to be better than the other cone models in terms of the input parameters of the WSA-ENLIL model.

Absence of S-cone input in human blindsight following hemispherectomy.

PubMed

Leh, Sandra E; Mullen, Kathy T; Ptito, Alain

2006-11-01

Destruction of the occipital cortex presumably leads to permanent blindness in the contralateral visual field. Residual abilities to respond to visual stimuli in the blind field without consciously experiencing them have, however, been described in cortically blind patients and are termed 'blindsight'. Although the neuronal basis of blindsight remains unknown, possible neuronal correlates have been proposed based on the nature of the residual vision observed. The most prominent but still controversial hypothesis postulates the involvement of the superior colliculi in blindsight. Here we demonstrate, using a computer-based reaction time test in a group of hemispherectomized subjects, that human 'attention-blindsight' can be measured for achromatic stimuli but disappears for stimuli that solely activate S-cones. Given that primate data have shown that the superior colliculi lacks input from S-cones, our results lend strong support to the hypothesis that 'attention-blindsight' is mediated through a collicular pathway. The contribution of a direct geniculo-extrastriate-koniocellular projection was ruled out by testing hemispherectomized subjects in whom a whole hemisphere has been removed or disconnected for the treatment of epilepsy. A direct retino-pulvinar-cortical connection is also unlikely as the pulvinar nucleus is known to receive input from S-cones as well as from L/M-cone-driven colour-opponent ganglion cells.

Luminance and chromatic signals interact differently with melanopsin activation to control the pupil light response.

PubMed

Barrionuevo, Pablo A; Cao, Dingcai

2016-09-01

Intrinsically photosensitive retinal ganglion cells (ipRGCs) express the photopigment melanopsin. These cells receive afferent inputs from rods and cones, which provide inputs to the postreceptoral visual pathways. It is unknown, however, how melanopsin activation is integrated with postreceptoral signals to control the pupillary light reflex. This study reports human flicker pupillary responses measured using stimuli generated with a five-primary photostimulator that selectively modulated melanopsin, rod, S-, M-, and L-cone excitations in isolation, or in combination to produce postreceptoral signals. We first analyzed the light adaptation behavior of melanopsin activation and rod and cones signals. Second, we determined how melanopsin is integrated with postreceptoral signals by testing with cone luminance, chromatic blue-yellow, and chromatic red-green stimuli that were processed by magnocellular (MC), koniocellular (KC), and parvocellular (PC) pathways, respectively. A combined rod and melanopsin response was also measured. The relative phase of the postreceptoral signals was varied with respect to the melanopsin phase. The results showed that light adaptation behavior for all conditions was weaker than typical Weber adaptation. Melanopsin activation combined linearly with luminance, S-cone, and rod inputs, suggesting the locus of integration with MC and KC signals was retinal. The melanopsin contribution to phasic pupil responses was lower than luminance contributions, but much higher than S-cone contributions. Chromatic red-green modulation interacted with melanopsin activation nonlinearly as described by a "winner-takes-all" process, suggesting the integration with PC signals might be mediated by a postretinal site.

Biallelic Mutations in GNB3 Cause a Unique Form of Autosomal-Recessive Congenital Stationary Night Blindness

PubMed Central

Vincent, Ajoy; Audo, Isabelle; Tavares, Erika; Maynes, Jason T.; Tumber, Anupreet; Wright, Thomas; Li, Shuning; Michiels, Christelle; Banin, Eyal; Bocquet, Beatrice; De Baere, Elfride; Casteels, Ingele; Defoort-Dhellemmes, Sabine; Drumare, Isabelle; Friedburg, Christoph; Gottlob, Irene; Jacobson, Samuel G.; Kellner, Ulrich; Koenekoop, Robert; Kohl, Susanne; Leroy, Bart P.; Lorenz, Birgit; McLean, Rebecca; Meire, Francoise; Meunier, Isabelle; Munier, Francis; de Ravel, Thomy; Reiff, Charlotte M.; Mohand-Saïd, Saddek; Sharon, Dror; Schorderet, Daniel; Schwartz, Sharon; Zanlonghi, Xavier; Condroyer, Christel; MacDonald, Heather; Verdet, Robert; Sahel, José-Alain; Hamel, Christian P.; Zeitz, Christina; Héon, Elise

2016-01-01

Congenital stationary night blindness (CSNB) is a heterogeneous group of non-progressive inherited retinal disorders with characteristic electroretinogram (ERG) abnormalities. Riggs and Schubert-Bornschein are subtypes of CSNB and demonstrate distinct ERG features. Riggs CSNB demonstrates selective rod photoreceptor dysfunction and occurs due to mutations in genes encoding proteins involved in rod phototransduction cascade; night blindness is the only symptom and eye examination is otherwise normal. Schubert-Bornschein CSNB is a consequence of impaired signal transmission between the photoreceptors and bipolar cells. Schubert-Bornschein CSNB is subdivided into complete CSNB with an ON bipolar signaling defect and incomplete CSNB with both ON and OFF pathway involvement. Both subtypes are associated with variable degrees of night blindness or photophobia, reduced visual acuity, high myopia, and nystagmus. Whole-exome sequencing of a family screened negative for mutations in genes associated with CSNB identified biallelic mutations in the guanine nucleotide-binding protein subunit beta-3 gene (GNB3). Two siblings were compound heterozygous for a deletion (c.170_172delAGA [p.Lys57del]) and a nonsense mutation (c.1017G>A [p.Trp339∗]). The maternal aunt was homozygous for the nonsense mutation (c.1017G>A [p.Trp339∗]). Mutational analysis of GNB3 in a cohort of 58 subjects with CSNB identified a sporadic case individual with a homozygous GNB3 mutation (c.200C>T [p.Ser67Phe]). GNB3 encodes the β subunit of G protein heterotrimer (Gαβγ) and is known to modulate ON bipolar cell signaling and cone transducin function in mice. Affected human subjects showed an unusual CSNB phenotype with variable degrees of ON bipolar dysfunction and reduced cone sensitivity. This unique retinal disorder with dual anomaly in visual processing expands our knowledge about retinal signaling. PMID:27063057

Altered Expression of Retinal Molecular Markers in the Canine RPE65 Model of Leber Congenital Amaurosis

PubMed Central

Hernández, Maria; Pearce-Kelling, Susan E.; Rodriguez, F. David; Aguirre, Gustavo D.; Vecino, Elena

2010-01-01

Purpose. Leber congenital amaurosis (LCA) is a group of childhood-onset retinal diseases characterized by severe visual impairment or blindness. One form is caused by mutations in the RPE65 gene, which encodes the retinal pigment epithelium (RPE) isomerase. In this study, the retinal structure and expression of molecular markers for different retinal cell types were characterized, and differences between control and RPE65 mutant dogs during the temporal evolution of the disease were analyzed. Methods. Retinas from normal and mutant dogs of different ages were examined by immunofluorescence with a panel of 16 different antibodies. Results. Cones and rods were preserved in the mutant retinas, and the number of cones was normal. However, there was altered expression of cone arrestin and delocalization of rod opsin. The ON bipolar cells showed sprouting of the dendritic arbors toward the outer nuclear layer (ONL) and retraction of their axons in the inner nuclear layer (INL). A decreased expression of GABA, and an increased expression of intermediate filament glial markers was also found in the mutant retinas. These changes were more evident in the adult than the young mutant retinas. Conclusions. The structure of the retina is well preserved in the mutant retina, but several molecular changes take place in photoreceptors and in bipolar and amacrine cells. Some of these changes are structural, whereas others reflect a change in localization of the examined proteins. This study provides new information that can be applied to the interpretation of outcomes of retinal gene therapy in animal models and humans. PMID:20671290

Non-image Forming Light Detection by Melanopsin, Rhodopsin, and Long-Middlewave (L/W) Cone Opsin in the Subterranean Blind Mole Rat, Spalax Ehrenbergi: Immunohistochemical Characterization, Distribution, and Connectivity

PubMed Central

Esquiva, Gema; Avivi, Aaron; Hannibal, Jens

2016-01-01

The blind mole rat, Spalax ehrenbergi, can, despite severely degenerated eyes covered by fur, entrain to the daily light/dark cycle and adapt to seasonal changes due to an intact circadian timing system. The present study demonstrates that the Spalax retina contains a photoreceptor layer, an outer nuclear layer (ONL), an outer plexiform layer (OPL), an inner nuclear layer (INL), an inner plexiform layer (IPL), and a ganglion cell layer (GCL). By immunohistochemistry, the number of melanopsin (mRGCs) and non-melanopsin bearing retinal ganglion cells was analyzed in detail. Using the ganglion cell marker RNA-binding protein with multiple splicing (RBPMS) it was shown that the Spalax eye contains 890 ± 62 RGCs. Of these, 87% (752 ± 40) contain melanopsin (cell density 788 melanopsin RGCs/mm2). The remaining RGCs were shown to co-store Brn3a and calretinin. The melanopsin cells were located mainly in the GCL with projections forming two dendritic plexuses located in the inner part of the IPL and in the OPL. Few melanopsin dendrites were also found in the ONL. The Spalax retina is rich in rhodopsin and long/middle wave (L/M) cone opsin bearing photoreceptor cells. By using Ctbp2 as a marker for ribbon synapses, both rods and L/M cone ribbons containing pedicles in the OPL were found in close apposition with melanopsin dendrites in the outer plexus suggesting direct synaptic contact. A subset of cone bipolar cells and all photoreceptor cells contain recoverin while a subset of bipolar and amacrine cells contain calretinin. The calretinin expressing amacrine cells seemed to form synaptic contacts with rhodopsin containing photoreceptor cells in the OPL and contacts with melanopsin cell bodies and dendrites in the IPL. The study demonstrates the complex retinal circuitry used by the Spalax to detect light, and provides evidence for both melanopsin and non-melanopsin projecting pathways to the brain. PMID:27375437

Non-image Forming Light Detection by Melanopsin, Rhodopsin, and Long-Middlewave (L/W) Cone Opsin in the Subterranean Blind Mole Rat, Spalax Ehrenbergi: Immunohistochemical Characterization, Distribution, and Connectivity.

PubMed

Esquiva, Gema; Avivi, Aaron; Hannibal, Jens

2016-01-01

The blind mole rat, Spalax ehrenbergi, can, despite severely degenerated eyes covered by fur, entrain to the daily light/dark cycle and adapt to seasonal changes due to an intact circadian timing system. The present study demonstrates that the Spalax retina contains a photoreceptor layer, an outer nuclear layer (ONL), an outer plexiform layer (OPL), an inner nuclear layer (INL), an inner plexiform layer (IPL), and a ganglion cell layer (GCL). By immunohistochemistry, the number of melanopsin (mRGCs) and non-melanopsin bearing retinal ganglion cells was analyzed in detail. Using the ganglion cell marker RNA-binding protein with multiple splicing (RBPMS) it was shown that the Spalax eye contains 890 ± 62 RGCs. Of these, 87% (752 ± 40) contain melanopsin (cell density 788 melanopsin RGCs/mm(2)). The remaining RGCs were shown to co-store Brn3a and calretinin. The melanopsin cells were located mainly in the GCL with projections forming two dendritic plexuses located in the inner part of the IPL and in the OPL. Few melanopsin dendrites were also found in the ONL. The Spalax retina is rich in rhodopsin and long/middle wave (L/M) cone opsin bearing photoreceptor cells. By using Ctbp2 as a marker for ribbon synapses, both rods and L/M cone ribbons containing pedicles in the OPL were found in close apposition with melanopsin dendrites in the outer plexus suggesting direct synaptic contact. A subset of cone bipolar cells and all photoreceptor cells contain recoverin while a subset of bipolar and amacrine cells contain calretinin. The calretinin expressing amacrine cells seemed to form synaptic contacts with rhodopsin containing photoreceptor cells in the OPL and contacts with melanopsin cell bodies and dendrites in the IPL. The study demonstrates the complex retinal circuitry used by the Spalax to detect light, and provides evidence for both melanopsin and non-melanopsin projecting pathways to the brain.

Co-morbidity of bipolar affective disorder and obsessive compulsive disorder in a Bedford community psychiatry team.

PubMed

Darby, Laura; Agius, Mark; Zaman, Rashid

2011-09-01

This is a study of the prevalence and impact of co-existing bipolar affective disorder on patients with OCD, and the effect on their management within a community psychiatric team. We found that 16% of patients who visited psychiatric outpatients with a diagnosis of OCD had co-existing bipolar affective disorder. Of these the majority had bipolar affective disorder II (67%). Co-morbidity raised a number of challenges to patient management. Compared to the control group the patients with co-morbid bipolar affective disorder required a greater number of outpatients appointments, had a greater number of hospital admissions, were more likely to have been allocated a care coordinator and to have received psychological input.

A New Local Bipolar Autoassociative Memory Based on External Inputs of Discrete Recurrent Neural Networks With Time Delay.

PubMed

Zhou, Caigen; Zeng, Xiaoqin; Luo, Chaomin; Zhang, Huaguang

In this paper, local bipolar auto-associative memories are presented based on discrete recurrent neural networks with a class of gain type activation function. The weight parameters of neural networks are acquired by a set of inequalities without the learning procedure. The global exponential stability criteria are established to ensure the accuracy of the restored patterns by considering time delays and external inputs. The proposed methodology is capable of effectively overcoming spurious memory patterns and achieving memory capacity. The effectiveness, robustness, and fault-tolerant capability are validated by simulated experiments.In this paper, local bipolar auto-associative memories are presented based on discrete recurrent neural networks with a class of gain type activation function. The weight parameters of neural networks are acquired by a set of inequalities without the learning procedure. The global exponential stability criteria are established to ensure the accuracy of the restored patterns by considering time delays and external inputs. The proposed methodology is capable of effectively overcoming spurious memory patterns and achieving memory capacity. The effectiveness, robustness, and fault-tolerant capability are validated by simulated experiments.

On the dual-cone nature of the conical refraction phenomenon.

PubMed

Turpin, A; Loiko, Yu; Kalkandjiev, T K; Tomizawa, H; Mompart, J

2015-04-15

In conical refraction (CR), a focused Gaussian input beam passing through a biaxial crystal and parallel to one of the optic axes is transformed into a pair of concentric bright rings split by a dark (Poggendorff) ring at the focal plane. Here, we show the generation of a CR transverse pattern that does not present the Poggendorff fine splitting at the focal plane, i.e., it forms a single light ring. This light ring is generated from a nonhomogeneously polarized input light beam obtained by using a spatially inhomogeneous polarizer that mimics the characteristic CR polarization distribution. This polarizer allows modulating the relative intensity between the two CR light cones in accordance with the recently proposed dual-cone model of the CR phenomenon. We show that the absence of interfering rings at the focal plane is caused by the selection of one of the two CR cones.

Preparation of Horizontal Slices of Adult Mouse Retina for Electrophysiological Studies.

PubMed

Feigenspan, Andreas; Babai, Norbert Zsolt

2017-01-27

Vertical slice preparations are well established to study circuitry and signal transmission in the adult mammalian retina. The plane of sectioning in these preparations is perpendicular to the retinal surface, making it ideal for the study of radially oriented neurons like photoreceptors and bipolar cells. However, the large dendritic arbors of horizontal cells, wide-field amacrine cells, and ganglion cells are mostly truncated, leaving markedly reduced synaptic activity in these cells. Whereas ganglion cells and displaced amacrine cells can be studied in a whole-mounted preparation of the retina, horizontal cells and amacrine cells located in the inner nuclear layer are only poorly accessible for electrodes in whole retina tissue. To achieve maximum accessibility and synaptic integrity, we developed a horizontal slice preparation of the mouse retina, and studied signal transmission at the synapse between photoreceptors and horizontal cells. Horizontal sectioning allows (1) easy and unambiguous visual identification of horizontal cell bodies for electrode targeting, and (2) preservation of the extended horizontal cell dendritic fields, as a prerequisite for intact and functional cone synaptic input to horizontal cell dendrites. Horizontal cells from horizontal slices exhibited tonic synaptic activity in the dark, and they responded to brief flashes of light with a reduction of inward current and diminished synaptic activity. Immunocytochemical evidence indicates that almost all cones within the dendritic field of a horizontal cell establish synapses with its peripheral dendrites. The horizontal slice preparation is therefore well suited to study the physiological properties of horizontally extended retinal neurons as well as sensory signal transmission and integration across selected synapses.

Nested-cone transformer antenna

DOEpatents

Ekdahl, C.A.

1991-05-28

A plurality of conical transmission lines are concentrically nested to form an output antenna for pulsed-power, radio-frequency, and microwave sources. The diverging conical conductors enable a high power input density across a bulk dielectric to be reduced below a breakdown power density at the antenna interface with the transmitting medium. The plurality of cones maintain a spacing between conductors which minimizes the generation of high order modes between the conductors. Further, the power input feeds are isolated at the input while enabling the output electromagnetic waves to add at the transmission interface. Thus, very large power signals from a pulse rf, or microwave source can be radiated. 6 figures.

Nested-cone transformer antenna

DOEpatents

Ekdahl, Carl A.

1991-01-01

A plurality of conical transmission lines are concentrically nested to form n output antenna for pulsed-power, radio-frequency, and microwave sources. The diverging conical conductors enable a high power input density across a bulk dielectric to be reduced below a breakdown power density at the antenna interface with the transmitting medium. The plurality of cones maintain a spacing between conductors which minimizes the generation of high order modes between the conductors. Further, the power input feeds are isolated at the input while enabling the output electromagnetic waves to add at the transmission interface. Thus, very large power signals from a pulse rf, or microwave source can be radiated.

Negative electroretinograms in pericentral pigmentary retinal degeneration.

PubMed

Hotta, Kazuki; Kondo, Mineo; Nakamura, Makoto; Hotta, Junko; Terasaki, Hiroko; Miyake, Yozo; Hida, Tetsuo

2006-01-01

The clinical presentation and electrophysiological findings are described of three consecutive cases with pericentral pigmentary retinal degeneration. The responses to bright flashes after dark adaptation showed negative waveform shape in all cases. Rod responses were strongly reduced compared with cone responses. Cone electroretinograms elicited by long-duration stimuli showed greater loss of the on-response than the off-response. The ratio of the on-response amplitude to off-response amplitude of these patients (0.52 +/- 0.12; mean +/- SD, n = 6) was significantly smaller than that of normal subject (0.83 +/- 0.21; mean +/- SD, n = 8) (Mann-Whitney U-test, P < 0.01). The electrophysiological findings of these cases suggest a greater defect of inner retinal function, especially in transmission between photoreceptors and depolarizing bipolar cells.

The Expanding Bipolar Conic Shell of the Symbiotic Star AG Peg

NASA Astrophysics Data System (ADS)

Lee, Seong-Jae; Hyung, Siek

2018-06-01

Symbiotic stars are the most interesting since some systems are believed to host the most massive white dwarf, like SN Ia progenitors. Most recently, Lee and Hyung (2018, LH18) proposed a bipolar conic shell structure for the observed high expansion Hα and Hβ line profiles and other double peak lines observed in 1998 September (phase φ = 10.24): the physical conditions for the white dwarf luminosity and the ionized HII zone, responsible for double Gaussian optical lines including Balmer and Lyman line fluxes, were taken from the P-I model with gas density, nH = 109.85 cm-3 , while the column density for the scattering neutral zone was derived from the broader line components based on the result by Monte Carlo simulations. In this investigation, we examined whether the expanding shells of the bipolar conical geometry as proposed by LH18 would be able to form the other Hα and Hβ line profiles observed in other phases, φ = 11.56 and 11.98 (in 2001 August and 2002 August). We look into the kinematical property of the bipolar conic shell structure responsible for the HII and HI zones and then we discuss the secular variation of the broad line feature and the origin of the bipolar cone, i.e., part of a common envelope formed through the mass inflows from the giant star.

Theory of chromatic noise masking applied to testing linearity of S-cone detection mechanisms.

PubMed

Giulianini, Franco; Eskew, Rhea T

2007-09-01

A method for testing the linearity of cone combination of chromatic detection mechanisms is applied to S-cone detection. This approach uses the concept of mechanism noise, the noise as seen by a postreceptoral neural mechanism, to represent the effects of superposing chromatic noise components in elevating thresholds and leads to a parameter-free prediction for a linear mechanism. The method also provides a test for the presence of multiple linear detectors and off-axis looking. No evidence for multiple linear mechanisms was found when using either S-cone increment or decrement tests. The results for both S-cone test polarities demonstrate that these mechanisms combine their cone inputs nonlinearly.

The effect of actuator nozzle designs on the electrostatic charge generated in pressurised metered dose inhaler aerosols.

PubMed

Chen, Yang; Young, Paul M; Fletcher, David F; Chan, Hak Kim; Long, Edward; Lewis, David; Church, Tanya; Traini, Daniela

2015-04-01

To investigate the influence of different actuator nozzle designs on aerosol electrostatic charges and aerosol performances for pressurised metered dose inhalers (pMDIs). Four actuator nozzle designs (flat, curved flat, cone and curved cone) were manufactured using insulating thermoplastics (PET and PTFE) and conducting metal (aluminium) materials. Aerosol electrostatic profiles of solution pMDI formulations containing propellant HFA 134a with different ethanol concentration and/or model drug beclomethasone dipropionate (BDP) were studied using a modified electrical low-pressure impactor (ELPI) for all actuator designs and materials. The mass of the deposited drug was analysed using high performance liquid chromatography (HPLC). Both curved nozzle designs for insulating PET and PTFE actuators significantly influenced aerosol electrostatics and aerosol performance compared with conducting aluminium actuator, where reversed charge polarity and higher throat deposition were observed with pMDI formulation containing BDP. Results are likely due to the changes in plume geometry caused by the curved edge nozzle designs and the bipolar charging nature of insulating materials. This study demonstrated that actuator nozzle designs could significantly influence the electrostatic charges profiles and aerosol drug deposition pattern of pMDI aerosols, especially when using insulating thermoplastic materials where bipolar charging is more dominant.

Spatiochromatic Interactions between Individual Cone Photoreceptors in the Human Retina

PubMed Central

Sabesan, Ramkumar; Sincich, Lawrence C.

2017-01-01

A remarkable feature of human vision is that the retina and brain have evolved circuitry to extract useful spatial and spectral information from signals originating in a photoreceptor mosaic with trichromatic constituents that vary widely in their relative numbers and local spatial configurations. A critical early transformation applied to cone signals is horizontal-cell-mediated lateral inhibition, which imparts a spatially antagonistic surround to individual cone receptive fields, a signature inherited by downstream neurons and implicated in color signaling. In the peripheral retina, the functional connectivity of cone inputs to the circuitry that mediates lateral inhibition is not cone-type specific, but whether these wiring schemes are maintained closer to the fovea remains unsettled, in part because central retinal anatomy is not easily amenable to direct physiological assessment. Here, we demonstrate how the precise topography of the long (L)-, middle (M)-, and short (S)-wavelength-sensitive cones in the human parafovea (1.5° eccentricity) shapes perceptual sensitivity. We used adaptive optics microstimulation to measure psychophysical detection thresholds from individual cones with spectral types that had been classified independently by absorptance imaging. Measured against chromatic adapting backgrounds, the sensitivities of L and M cones were, on average, receptor-type specific, but individual cone thresholds varied systematically with the number of preferentially activated cones in the immediate neighborhood. The spatial and spectral patterns of these interactions suggest that interneurons mediating lateral inhibition in the central retina, likely horizontal cells, establish functional connections with L and M cones indiscriminately, implying that the cone-selective circuitry supporting red–green color vision emerges after the first retinal synapse. SIGNIFICANCE STATEMENT We present evidence for spatially antagonistic interactions between individual, spectrally typed cones in the central retina of human observers using adaptive optics. Using chromatic adapting fields to modulate the relative steady-state activity of long (L)- and middle (M)-wavelength-sensitive cones, we found that single-cone detection thresholds varied predictably with the spectral demographics of the surrounding cones. The spatial scale and spectral pattern of these photoreceptor interactions were consistent with lateral inhibition mediated by retinal horizontal cells that receive nonselective input from L and M cones. These results demonstrate a clear link between the neural architecture of the visual system inputs—cone photoreceptors—and visual perception and have implications for the neural locus of the cone-specific circuitry supporting color vision. PMID:28871030

Comparison of the WSA-ENLIL model with three CME cone types

NASA Astrophysics Data System (ADS)

Jang, Soojeong; Moon, Y.; Na, H.

2013-07-01

We have made a comparison of the CME-associated shock propagation based on the WSA-ENLIL model with three cone types using 29 halo CMEs from 2001 to 2002. These halo CMEs have cone model parameters as well as their associated interplanetary (IP) shocks. For this study we consider three different cone types (an asymmetric cone model, an ice-cream cone model and an elliptical cone model) to determine 3-D CME parameters (radial velocity, angular width and source location), which are the input values of the WSA-ENLIL model. The mean absolute error (MAE) of the arrival times for the asymmetric cone model is 10.6 hours, which is about 1 hour smaller than those of the other models. Their ensemble average of MAE is 9.5 hours. However, this value is still larger than that (8.7 hours) of the empirical model of Kim et al. (2007). We will compare their IP shock velocities and densities with those from ACE in-situ measurements and discuss them in terms of the prediction of geomagnetic storms.Abstract (2,250 Maximum Characters): We have made a comparison of the CME-associated shock propagation based on the WSA-ENLIL model with three cone types using 29 halo CMEs from 2001 to 2002. These halo CMEs have cone model parameters as well as their associated interplanetary (IP) shocks. For this study we consider three different cone types (an asymmetric cone model, an ice-cream cone model and an elliptical cone model) to determine 3-D CME parameters (radial velocity, angular width and source location), which are the input values of the WSA-ENLIL model. The mean absolute error (MAE) of the arrival times for the asymmetric cone model is 10.6 hours, which is about 1 hour smaller than those of the other models. Their ensemble average of MAE is 9.5 hours. However, this value is still larger than that (8.7 hours) of the empirical model of Kim et al. (2007). We will compare their IP shock velocities and densities with those from ACE in-situ measurements and discuss them in terms of the prediction of geomagnetic storms.

Precision absolute-value amplifier for a precision voltmeter

DOEpatents

Hearn, W.E.; Rondeau, D.J.

1982-10-19

Bipolar inputs are afforded by the plus inputs of first and second differential input amplifiers. A first gain determining resistor is connected between the minus inputs of the differential amplifiers. First and second diodes are connected between the respective minus inputs and the respective outputs of the differential amplifiers. First and second FETs have their gates connected to the outputs of the amplifiers, while their respective source and drain circuits are connected between the respective minus inputs and an output lead extending to a load resistor. The output current through the load resistor is proportional to the absolute value of the input voltage difference between the bipolar input terminals. A third differential amplifier has its plus input terminal connected to the load resistor. A second gain determining resistor is connected between the minus input of the third differential amplifier and a voltage source. A third FET has its gate connected to the output of the third amplifier. The source and drain circuit of the third transistor is connected between the minus input of the third amplifier and a voltage-frequency converter, constituting an output device. A polarity detector is also provided, comprising a pair of transistors having their inputs connected to the outputs of the first and second differential amplifiers. The outputs of the polarity detector are connected to gates which switch the output of the voltage-frequency converter between up and down counting outputs.

Precision absolute value amplifier for a precision voltmeter

DOEpatents

Hearn, William E.; Rondeau, Donald J.

1985-01-01

Bipolar inputs are afforded by the plus inputs of first and second differential input amplifiers. A first gain determining resister is connected between the minus inputs of the differential amplifiers. First and second diodes are connected between the respective minus inputs and the respective outputs of the differential amplifiers. First and second FETs have their gates connected to the outputs of the amplifiers, while their respective source and drain circuits are connected between the respective minus inputs and an output lead extending to a load resister. The output current through the load resister is proportional to the absolute value of the input voltage difference between the bipolar input terminals. A third differential amplifier has its plus input terminal connected to the load resister. A second gain determining resister is connected between the minus input of the third differential amplifier and a voltage source. A third FET has its gate connected to the output of the third amplifier. The source and drain circuit of the third transistor is connected between the minus input of the third amplifier and a voltage-frequency converter, constituting an output device. A polarity detector is also provided, comprising a pair of transistors having their inputs connected to the outputs of the first and second differential amplifiers. The outputs of the polarity detector are connected to gates which switch the output of the voltage-frequency converter between up and down counting outputs.

Comparison of the human multifocal electroretinogram a-wave response and adaptive optics imaging of cone photoreceptor numbers

NASA Astrophysics Data System (ADS)

Klein, Michael W.

Studies that have used pharmacological agents in non human primates (e.g., Hood et al., IOVS 2002) indicate that electrical activity of cone photoreceptors, depolarizing cone bipolar cells and horizontal cells are all likely to contribute to the multifocal electroretinogram (mfERG) a-wave. The purpose of this study was to examine the relationship between the mfERG a-wave and co-localized cone spatial density individually measured in young healthy human subjects. mfERGs (0.1-300Hz) were recorded from 4 subjects (20-29 years) with a system from Veris Science (EDI, Inc.) using 2.4 degree unstretched hexagons from 206 retinal locations presented at 30 frames per m-step on a 75Hz monitor with m-sequence exponent of 9 and flash strength 9.9 cd-s/m 2. mfERG a-wave amplitude was measured from baseline at 10 milliseconds on the leading edge of the a-wave. In vivo cone images were obtained at 24 retinal locations using a custom-built Adaptive Optics Confocal Scanning Laser Ophthalmoscope. Cone spatial density was measured from a 100x100mum centered on the mfERG hexagons at 24 retinal locations. mfERG a-wave amplitude as well as cone density reduced with increase in retinal eccentricity from the fovea and the a-wave amplitude and cone density were positively correlated for each subject (r2=0.35 to 0.49 and p = 0.0049 to 0.0002). The coefficient of variation (CV) of the mfERG a-wave amplitude across subjects at each retinal location (16-62%) was larger than the CV of the cone density (8-37%) at the same location. The results indicate that underlying cone density accounts for a significant portion (up to nearly 70%) of the variance in the mfERG a-wave amplitude across retinal eccentricity. Other factors likely contribute to the variance (approximately 30%) of the measured mfERG parameters.

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

PubMed

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 responses of transient OFF-α retinal ganglion cells in a newly generated mouse line. In this mouse line, horizontal cell signals were no longer modulated by light. With light response recordings, we show that horizontal cells increase the dynamic range of retinal ganglion cells for contrast and temporal changes and contribute to the center/surround organization of their receptive fields. Copyright © 2018 the authors 0270-6474/18/382015-14$15.00/0.

Bhlhb5 is Required for the Subtype Development of Retinal Amacrine and Bipolar Cells in Mice

PubMed Central

Huang, Liang; Hu, Fang; Feng, Liang; Luo, Xiong-Jian; Liang, Guoqing; Zeng, Xiang-Yun; Yi, Jing-Lin; Gan, Lin

2014-01-01

Background BHLHB5, an OLIG-related basic helix-loop-helix transcription factor, is required for the development of a subset of gamma-amino butyric acid–releasing (GABAergic) amacrine cells and OFF-cone bipolar (CB) cells in mouse retinas. In order to determine BHLHB5’s functional mechanism in retinogenesis, we used the Cre-loxP recombination system to genetically trace the lineage of BHLHB5+ cells in normal and Bhlhb5-null retinas. The Bhlhb5-Cre knock-in allele was used to activate the constitutive expression of a GFP reporter in the Bhlhb5-expressing cells, and the cell fates of Bhlhb5-lineage cells were identified by using specific cell markers and were compared between normal and Bhlhb5-null retinas. Results In addition to GABAergic amacrine and OFF-CB cells, Bhlhb5 lineage cells give rise to ganglion, glycinergic amacrine, rod bipolar, ON-bipolar, and rod photoreceptor cells during normal retinal development. Targeted deletion of Bhlhb5 resulted in the loss of GABAergic amacrine, glycinergic amacrine, dopaminergic amacrine, and Type 2 OFF-CB cells. Furthermore, in the absence of BHLHB5, a portion of Bhlhb5 lineage cells switch their fate and differentiate into cholinergic amacrine cells. Conclusions Our data reveal a broad expression pattern of Bhlhb5 throughout retinogenesis and demonstrate the cell-autonomous as well as non-cell-autonomous role of Bhlhb5 in the specification of amacrine and bipolar subtypes. PMID:24123365

Bhlhb5 is required for the subtype development of retinal amacrine and bipolar cells in mice.

PubMed

Huang, Liang; Hu, Fang; Feng, Liang; Luo, Xiong-Jian; Liang, Guoqing; Zeng, Xiang-Yun; Yi, Jing-Lin; Gan, Lin

2014-02-01

BHLHB5, an OLIG-related basic helix-loop-helix transcription factor, is required for the development of a subset of gamma-amino butyric acid-releasing (GABAergic) amacrine cells and OFF-cone bipolar (CB) cells in mouse retinas. In order to determine BHLHB5's functional mechanism in retinogenesis, we used the Cre-loxP recombination system to genetically trace the lineage of BHLHB5+ cells in normal and Bhlhb5-null retinas. The Bhlhb5-Cre knock-in allele was used to activate the constitutive expression of a GFP reporter in the Bhlhb5-expressing cells, and the cell fates of Bhlhb5-lineage cells were identified by using specific cell markers and were compared between normal and Bhlhb5-null retinas. In addition to GABAergic amacrine and OFF-CB cells, Bhlhb5 lineage cells give rise to ganglion, glycinergic amacrine, rod bipolar, ON-bipolar, and rod photoreceptor cells during normal retinal development. Targeted deletion of Bhlhb5 resulted in the loss of GABAergic amacrine, glycinergic amacrine, dopaminergic amacrine, and Type 2 OFF-CB cells. Furthermore, in the absence of BHLHB5, a portion of Bhlhb5 lineage cells switch their fate and differentiate into cholinergic amacrine cells. Our data reveal a broad expression pattern of Bhlhb5 throughout retinogenesis and demonstrate the cell-autonomous as well as non-cell-autonomous role of Bhlhb5 in the specification of amacrine and bipolar subtypes. Copyright © 2013 Wiley Periodicals, Inc.

Adeno-associated virus-RNAi of GlyRα1 and characterization of its synapse-specific inhibition in OFF alpha transient retinal ganglion cells

PubMed Central

Zhang, C.; Rompani, S. B.; Roska, B.

2014-01-01

In the central nervous system, inhibition shapes neuronal excitation. In spinal cord glycinergic inhibition predominates, whereas GABAergic inhibition predominates in the brain. The retina uses GABA and glycine in approximately equal proportions. Glycinergic crossover inhibition, initiated in the On retinal pathway, controls glutamate release from presynaptic OFF cone bipolar cells (CBCs) and directly shapes temporal response properties of OFF retinal ganglion cells (RGCs). In the retina, four glycine receptor (GlyR) α-subunit isoforms are expressed in different sublaminae and their synaptic currents differ in decay kinetics. GlyRα1, expressed in both On and Off sublaminae of the inner plexiform layer, could be the glycinergic isoform that mediates On-to-Off crossover inhibition. However, subunit-selective glycine contributions remain unknown because we lack selective antagonists or cell class-specific subunit knockouts. To examine the role of GlyRα1 in direct inhibition in mature RGCs, we used retrogradely transported adeno-associated virus (AAV) that performed RNAi and eliminated almost all glycinergic spontaneous and visually evoked responses in PV5 (OFFαTransient) RGCs. Comparisons of responses in PV5 RGCs infected with AAV-scrambled-short hairpin RNA (shRNA) or AAV-Glra1-shRNA confirm a role for GlyRα1 in crossover inhibition in cone-driven circuits. Our results also define a role for direct GlyRα1 inhibition in setting the resting membrane potential of PV5 RGCs. The absence of GlyRα1 input unmasked a serial and a direct feedforward GABAAergic modulation in PV5 RGCs, reflecting a complex interaction between glycinergic and GABAAergic inhibition. PMID:25231618

Chapter 51: How to Build a Simple Cone Search Service Using a Local Database

NASA Astrophysics Data System (ADS)

Kent, B. R.; Greene, G. R.

The cone search service protocol will be examined from the server side in this chapter. A simple cone search service will be setup and configured locally using MySQL. Data will be read into a table, and the Java JDBC will be used to connect to the database. Readers will understand the VO cone search specification and how to use it to query a database on their local systems and return an XML/VOTable file based on an input of RA/DEC coordinates and a search radius. The cone search in this example will be deployed as a Java servlet. The resulting cone search can be tested with a verification service. This basic setup can be used with other languages and relational databases.

Quantal amplitude at the cone ribbon synapse can be adjusted by changes in cytosolic glutamate

PubMed Central

Bartoletti, Theodore M.

2011-01-01

Purpose Vision is encoded at photoreceptor synapses by the number of released vesicles and size of the post-synaptic response. We hypothesized that elevating cytosolic glutamate could enhance quantal size by increasing glutamate in vesicles. Methods We introduced glutamate (10–40 mM) into cone terminals through a patch pipette and recorded excitatory post-synaptic currents (EPSCs) from horizontal or OFF bipolar cells in the Ambystoma tigrinum retinal slice preparation. Results Elevating cytosolic glutamate in cone terminals enhanced EPSCs as well as quantal miniature EPSCs (mEPSCs). Enhancement was prevented by inhibiting vesicular glutamate transport with 1S,3R-1-aminocyclopentane-1,3-dicarboxylate in the patch pipette. A low affinity glutamate receptor antagonist, γD-glutamylglycine (1 mM), less effectively inhibited EPSCs evoked from cones loaded with glutamate than control cones indicating that release from cones with supplemental glutamate produced higher glutamate levels in the synaptic cleft. Raising presynaptic glutamate did not alter exocytotic capacitance responses and exocytosis was observed after inhibiting glutamate loading with the vesicular ATPase inhibitor, concanamycin A, suggesting that release capability is not restricted by low vesicular glutamate levels. Variance-mean analysis of currents evoked by flash photolysis of caged glutamate indicated that horizontal cell AMPA receptors have a single channel conductance of 10.1 pS suggesting that ~8.7 GluRs contribute to each mEPSC. Conclusions Quantal amplitude at the cone ribbon synapse is capable of adjustment by changes in cytosolic glutamate levels. The small number of channels contributing to each mEPSC suggests that stochastic variability in channel opening could be an important source of quantal variability. PMID:21541265

Lithium alters the morphology of neurites regenerating from cultured adult spiral ganglion neurons.

PubMed

Shah, S M; Patel, C H; Feng, A S; Kollmar, R

2013-10-01

The small-molecule drug lithium (as a monovalent ion) promotes neurite regeneration and functional recovery, is easy to administer, and is approved for human use to treat bipolar disorder. Lithium exerts its neuritogenic effect mainly by inhibiting glycogen synthase kinase 3, a constitutively-active serine/threonine kinase that is regulated by neurotrophin and "wingless-related MMTV integration site" (Wnt) signaling. In spiral ganglion neurons of the cochlea, the effects of lithium and the function of glycogen synthase kinase 3 have not been investigated. We, therefore, set out to test whether lithium modulates neuritogenesis from adult spiral ganglion neurons. Primary cultures of dissociated spiral ganglion neurons from adult mice were exposed to lithium at concentrations between 0 and 12.5 mM. The resulting neurite morphology and growth-cone appearance were measured in detail by using immunofluorescence microscopy and image analysis. We found that lithium altered the morphology of regenerating neurites and their growth cones in a differential, concentration-dependent fashion. Low concentrations of 0.5-2.5 mM (around the half-maximal inhibitory concentration for glycogen synthase kinase 3 and the recommended therapeutic serum concentration for bipolar disorder) enhanced neurite sprouting and branching. A high concentration of 12.5 mM, in contrast, slowed elongation. As the lithium concentration rose from low to high, the microtubules became increasingly disarranged and the growth cones more arborized. Our results demonstrate that lithium selectively stimulates phases of neuritogenesis that are driven by microtubule reorganization. In contrast, most other drugs that have previously been tested on spiral ganglion neurons are reported to inhibit neurite outgrowth or affect only elongation. Lithium sensitivity is a necessary, but not sufficient condition for the involvement of glycogen synthase kinase 3. Our results are, therefore, consistent with, but do not prove lithium inhibiting glycogen synthase kinase 3 activity in spiral ganglion neurons. Experiments with additional drugs and molecular-genetic tools will be necessary to test whether glycogen synthase kinase 3 regulates neurite regeneration from spiral ganglion neurons, possibly by integrating neurotrophin and Wnt signals at the growth cone. Copyright © 2013 Elsevier B.V. All rights reserved.

Field effect transistors improve buffer amplifier

NASA Technical Reports Server (NTRS)

1967-01-01

Unity gain buffer amplifier with a Field Effect Transistor /FET/ differential input stage responds much faster than bipolar transistors when operated at low current levels. The circuit uses a dual FET in a unity gain buffer amplifier having extremely high input impedance, low bias current requirements, and wide bandwidth.

Gene therapy rescues photoreceptor blindness in dogs and paves the way for treating human X-linked retinitis pigmentosa.

PubMed

Beltran, William A; Cideciyan, Artur V; Lewin, Alfred S; Iwabe, Simone; Khanna, Hemant; Sumaroka, Alexander; Chiodo, Vince A; Fajardo, Diego S; Román, Alejandro J; Deng, Wen-Tao; Swider, Malgorzata; Alemán, Tomas S; Boye, Sanford L; Genini, Sem; Swaroop, Anand; Hauswirth, William W; Jacobson, Samuel G; Aguirre, Gustavo D

2012-02-07

Hereditary retinal blindness is caused by mutations in genes expressed in photoreceptors or retinal pigment epithelium. Gene therapy in mouse and dog models of a primary retinal pigment epithelium disease has already been translated to human clinical trials with encouraging results. Treatment for common primary photoreceptor blindness, however, has not yet moved from proof of concept to the clinic. We evaluated gene augmentation therapy in two blinding canine photoreceptor diseases that model the common X-linked form of retinitis pigmentosa caused by mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene, which encodes a photoreceptor ciliary protein, and provide evidence that the therapy is effective. After subretinal injections of adeno-associated virus-2/5-vectored human RPGR with human IRBP or GRK1 promoters, in vivo imaging showed preserved photoreceptor nuclei and inner/outer segments that were limited to treated areas. Both rod and cone photoreceptor function were greater in treated (three of four) than in control eyes. Histopathology indicated normal photoreceptor structure and reversal of opsin mislocalization in treated areas expressing human RPGR protein in rods and cones. Postreceptoral remodeling was also corrected: there was reversal of bipolar cell dendrite retraction evident with bipolar cell markers and preservation of outer plexiform layer thickness. Efficacy of gene therapy in these large animal models of X-linked retinitis pigmentosa provides a path for translation to human treatment.

Functional and Physical Outcomes following Use of a Flexible CO2 Laser Fiber and Bipolar Electrocautery in Close Proximity to the Rat Sciatic Nerve with Correlation to an In Vitro Thermal Profile Model

PubMed Central

Robinson, A. M.; Fishman, A. J.; Bendok, B. R.; Richter, C.-P.

2015-01-01

This study compared functional and physical collateral damage to a nerve when operating a Codman MALIS Bipolar Electrosurgical System CMC-III or a CO2 laser coupled to a laser, with correlation to an in vitro model of heating profiles created by the devices in thermochromic ink agarose. Functional damage of the rat sciatic nerve after operating the MALIS or CO2 laser at various power settings and proximities to the nerve was measured by electrically evoked nerve action potentials, and histology of the nerve was used to assess physical damage. Thermochromic ink dissolved in agarose was used to model the spatial and temporal profile of the collateral heating zone of the electrosurgical system and the laser ablation cone. We found that this laser can be operated at 2 W directly above the nerve with minimal damage, while power settings of 5 W and 10 W resulted in acute functional and physical nerve damage, correlating with the maximal heating cone in the thermochromic ink model. MALIS settings up to 40 (11 W) did not result in major functional or physical nerve damage until the nerve was between the forceps tips, correlating with the hottest zone, localized discretely between the tips. PMID:25699266

AII amacrine cells discriminate between heterocellular and homocellular locations when assembling connexin36-containing gap junctions

PubMed Central

Meyer, Arndt; Hilgen, Gerrit; Dorgau, Birthe; Sammler, Esther M.; Weiler, Reto; Monyer, Hannah; Dedek, Karin; Hormuzdi, Sheriar G.

2014-01-01

ABSTRACT Electrical synapses (gap junctions) rapidly transmit signals between neurons and are composed of connexins. In neurons, connexin36 (Cx36) is the most abundant isoform; however, the mechanisms underlying formation of Cx36-containing electrical synapses are unknown. We focus on homocellular and heterocellular gap junctions formed by an AII amacrine cell, a key interneuron found in all mammalian retinas. In mice lacking native Cx36 but expressing a variant tagged with enhanced green fluorescent protein at the C-terminus (KO-Cx36-EGFP), heterocellular gap junctions formed between AII cells and ON cone bipolar cells are fully functional, whereas homocellular gap junctions between two AII cells are not formed. A tracer injected into an AII amacrine cell spreads into ON cone bipolar cells but is excluded from other AII cells. Reconstruction of Cx36–EGFP clusters on an AII cell in the KO-Cx36-EGFP genotype confirmed that the number, but not average size, of the clusters is reduced – as expected for AII cells lacking a subset of electrical synapses. Our studies indicate that some neurons exhibit at least two discriminatory mechanisms for assembling Cx36. We suggest that employing different gap-junction-forming mechanisms could provide the means for a cell to regulate its gap junctions in a target-cell-specific manner, even if these junctions contain the same connexin. PMID:24463820

Comparison of the CME-associated shock arrival times at the earth using the WSA-ENLIL model with three cone models

NASA Astrophysics Data System (ADS)

Jang, S.; Moon, Y.; Na, H.

2012-12-01

We have made a comparison of CME-associated shock arrival times at the earth based on the WSA-ENLIL model with three cone models using 29 halo CMEs from 2001 to 2002. These halo CMEs have cone model parameters from Michalek et al. (2007) as well as their associated interplanetary (IP) shocks. For this study we consider three different cone models (an asymmetric cone model, an ice-cream cone model and an elliptical cone model) to determine CME cone parameters (radial velocity, angular width and source location), which are used for input parameters of the WSA-ENLIL model. The mean absolute error (MAE) of the arrival times for the elliptical cone model is 10 hours, which is about 2 hours smaller than those of the other models. However, this value is still larger than that (8.7 hours) of an empirical model by Kim et al. (2007). We are investigating several possibilities on relatively large errors of the WSA-ENLIL cone model, which may be caused by CME-CME interaction, background solar wind speed, and/or CME density enhancement.

Excitatory synaptic inputs to mouse on-off direction-selective retinal ganglion cells lack direction tuning.

PubMed

Park, Silvia J H; Kim, In-Jung; Looger, Loren L; Demb, Jonathan B; Borghuis, Bart G

2014-03-12

Direction selectivity represents a fundamental visual computation. In mammalian retina, On-Off direction-selective ganglion cells (DSGCs) respond strongly to motion in a preferred direction and weakly to motion in the opposite, null direction. Electrical recordings suggested three direction-selective (DS) synaptic mechanisms: DS GABA release during null-direction motion from starburst amacrine cells (SACs) and DS acetylcholine and glutamate release during preferred direction motion from SACs and bipolar cells. However, evidence for DS acetylcholine and glutamate release has been inconsistent and at least one bipolar cell type that contacts another DSGC (On-type) lacks DS release. Here, whole-cell recordings in mouse retina showed that cholinergic input to On-Off DSGCs lacked DS, whereas the remaining (glutamatergic) input showed apparent DS. Fluorescence measurements with the glutamate biosensor intensity-based glutamate-sensing fluorescent reporter (iGluSnFR) conditionally expressed in On-Off DSGCs showed that glutamate release in both On- and Off-layer dendrites lacked DS, whereas simultaneously recorded excitatory currents showed apparent DS. With GABA-A receptors blocked, both iGluSnFR signals and excitatory currents lacked DS. Our measurements rule out DS release from bipolar cells onto On-Off DSGCs and support a theoretical model suggesting that apparent DS excitation in voltage-clamp recordings results from inadequate voltage control of DSGC dendrites during null-direction inhibition. SAC GABA release is the apparent sole source of DS input onto On-Off DSGCs.

Mouse rods signal through gap junctions with cones.

PubMed

Asteriti, Sabrina; Gargini, Claudia; Cangiano, Lorenzo

2014-01-01

Rod and cone photoreceptors are coupled by gap junctions (GJs), relatively large channels able to mediate both electrical and molecular communication. Despite their critical location in our visual system and evidence that they are dynamically gated for dark/light adaptation, the full impact that rod-cone GJs can have on cone function is not known. We recorded the photovoltage of mouse cones and found that the initial level of rod input increased spontaneously after obtaining intracellular access. This process allowed us to explore the underlying coupling capacity to rods, revealing that fully coupled cones acquire a striking rod-like phenotype. Calcium, a candidate mediator of the coupling process, does not appear to be involved on the cone side of the junctional channels. Our findings show that the anatomical substrate is adequate for rod-cone coupling to play an important role in vision and, possibly, in biochemical signaling among photoreceptors. DOI: http://dx.doi.org/10.7554/eLife.01386.001.

Mouse rods signal through gap junctions with cones

PubMed Central

Asteriti, Sabrina; Gargini, Claudia; Cangiano, Lorenzo

2014-01-01

Rod and cone photoreceptors are coupled by gap junctions (GJs), relatively large channels able to mediate both electrical and molecular communication. Despite their critical location in our visual system and evidence that they are dynamically gated for dark/light adaptation, the full impact that rod–cone GJs can have on cone function is not known. We recorded the photovoltage of mouse cones and found that the initial level of rod input increased spontaneously after obtaining intracellular access. This process allowed us to explore the underlying coupling capacity to rods, revealing that fully coupled cones acquire a striking rod-like phenotype. Calcium, a candidate mediator of the coupling process, does not appear to be involved on the cone side of the junctional channels. Our findings show that the anatomical substrate is adequate for rod–cone coupling to play an important role in vision and, possibly, in biochemical signaling among photoreceptors. DOI: http://dx.doi.org/10.7554/eLife.01386.001 PMID:24399457

Machine Visual Motion Detection Modeled on Vertebrate Retina

DTIC Science & Technology

1988-01-01

18. NUMBER OF PAGES 9 19a. NAME OF RESPONSIBLE PERSON a. REPORT unclassified b . ABSTRACT unclassified c. THIS PAGE unclassified Standard Form...mechanism of direction selectivity. (a) shows the use of persistent lateral inhibition to block conduction in the null direction. ( b ) shows the use of...Bipolar elements Bipolar ( B ) elements compare the inputs from local receptor and horizontal elements, passing on the positive value of the difference

Hypothesis on human eye perceiving optical spectrum rather than an image

NASA Astrophysics Data System (ADS)

Zheng, Yufeng; Szu, Harold

2015-05-01

It is a common knowledge that we see the world because our eyes can perceive an optical image. A digital camera seems a good example of simulating the eye imaging system. However, the signal sensing and imaging on human retina is very complicated. There are at least five layers (of neurons) along the signal pathway: photoreceptors (cones and rods), bipolar, horizontal, amacrine and ganglion cells. To sense an optical image, it seems that photoreceptors (as sensors) plus ganglion cells (converting to electrical signals for transmission) are good enough. Image sensing does not require ununiformed distribution of photoreceptors like fovea. There are some challenging questions, for example, why don't we feel the "blind spots" (never fibers exiting the eyes)? Similar situation happens to glaucoma patients who do not feel their vision loss until 50% or more nerves died. Now our hypothesis is that human retina initially senses optical (i.e., Fourier) spectrum rather than optical image. Due to the symmetric property of Fourier spectrum the signal loss from a blind spot or the dead nerves (for glaucoma patients) can be recovered. Eye logarithmic response to input light intensity much likes displaying Fourier magnitude. The optics and structures of human eyes satisfy the needs of optical Fourier spectrum sampling. It is unsure that where and how inverse Fourier transform is performed in human vision system to obtain an optical image. Phase retrieval technique in compressive sensing domain enables image reconstruction even without phase inputs. The spectrum-based imaging system can potentially tolerate up to 50% of bad sensors (pixels), adapt to large dynamic range (with logarithmic response), etc.

S-cone discrimination in the presence of two adapting fields: data and model

PubMed Central

Cao, Dingcai

2014-01-01

This study investigated S-cone discrimination using a test annulus surrounded by an inner and outer adapting field with systematic manipulation of the adapting l = L/(L + M) or s = S/(L + M) chromaticities. The results showed that different adapting l chromaticities altered S-cone discrimination for a high adapting s chromaticity due to parvocellular input to the koniocellular pathway. In addition, S-cone discrimination was determined by the combined spectral signals arising from both adapting fields. The “white” adapting field or an adapting field with a different l chromaticity from the other fields was more likely to have a stronger influence on discrimination thresholds. These results indicated that the two cardinal axes are not independent in S-cone discrimination, and the two adapting fields jointly contribute to S-cone discrimination through a cortical summation mechanism. PMID:24695204

Correlated cone noise decreases rod signal contributions to the post-receptoral pathways.

PubMed

Hathibelagal, Amithavikram R; Feigl, Beatrix; Zele, Andrew J

2018-04-01

This study investigated how invisible extrinsic temporal white noise that correlates with the activity of one of the three [magnocellular (MC), parvocellular (PC), or koniocellular (KC)] post-receptoral pathways alters mesopic rod signaling. A four-primary photostimulator provided independent control of the rod and three cone photoreceptor excitations. The rod contributions to the three post-receptoral pathways were estimated by perceptually matching a 20% contrast rod pulse by independently varying the LMS (MC pathway), +L-M (PC pathway), and S-cone (KC pathway) excitations. We show that extrinsic cone noise caused a predominant decrease in the overall magnitude and ratio of the rod contributions to each pathway. Thus, the relative cone activity in the post-receptoral pathways determines the relative mesopic rod inputs to each pathway.

The Tin Bider Impact Structure, Algeria: New Map with Field Inputs on Structural Aspect

NASA Astrophysics Data System (ADS)

Kassab, F.; Belhai, D.

2017-07-01

The Tin Bider impact structure is a complex type composed by sedimentary target rocks. We realized a geological map including new inputs on impact characters of a recent field investigation where we identify shatter cone and folds.

Calcium regulates vesicle replenishment at the cone ribbon synapse

PubMed Central

Babai, Norbert; Bartoletti, Theodore M.; Thoreson, Wallace B.

2010-01-01

Cones release glutamate-filled vesicles continuously in darkness and changing illumination modulates this release. Because sustained release in darkness is governed by vesicle replenishment rates, we analyzed how cone membrane potential regulates replenishment. Synaptic release from cones was measured by recording post-synaptic currents in Ambystoma tigrinum horizontal or OFF bipolar cells evoked by depolarization of simultaneously voltage-clamped cones. We measured replenishment after attaining a steady-state between vesicle release and replenishment using trains of test pulses. Increasing Ca2+ currents (ICa) by changing the test step from −30 to −10 mV increased replenishment. Lengthening −30 mV test pulses to match the Ca2+ influx during 25 ms test pulses to −10 mV produced similar replenishment rates. Reducing Ca2+ driving force by using test steps to +30 mV slowed replenishment. Using UV flashes to reverse inhibition of ICa by nifedipine accelerated replenishment. Increasing [Ca2+]i by flash photolysis of caged Ca2+ also accelerated replenishment. Replenishment, but not the initial burst of release, was enhanced by using an intracellular Ca2+ buffer of 0.5 mM EGTA rather than 5 mM EGTA, and diminished by 1 mM BAPTA. This suggests that although release and replenishment and release exhibited similar Ca2+-dependencies, release sites are <200 nm from Ca2+ channels but replenishment sites are >200 nm away. Membrane potential thus regulates replenishment by controlling Ca2+ influx, principally by effects on replenishment mechanisms but also by altering releasable pool size. This in turn provides a mechanism for converting changes in light intensity into changes in sustained release at the cone ribbon synapse. PMID:21106825

Advanced designs for non-imaging submillimeter-wave Winston cone concentrators

NASA Astrophysics Data System (ADS)

Nelson, A. O.; Grossman, E. N.

2014-05-01

We describe the design and simulation of several non-imaging concentrators designed to couple submillimeter wavelength radiation from free space into highly overmoded, rectangular, WR-10 waveguide. Previous designs are altered to improve the uniformity of efficiency rather than the efficiency itself. The concentrators are intended for use as adapters between instruments using overmoded WR-10 waveguide as input or output and sources propagating through free space. Previous simulation and measurement have shown that the angular response is primarily determined by the Winston cone and is well predicted by geometric optics theory while the efficiencies are primarily determined by the transition section. Additionally, previous work has shown insensitivity to polarization, orientation and beam size. Several separate concentrator designs are studied, all of which use a Winston cone (also known as a compound parabolic concentrator) with an input diameter ranging from 4 mm to 16 mm, and "throat" diameters of less than 0.5 mm to 4 mm as the initial interface. The use of various length adiabatic circular-to-rectangular transition sections is investigated, along with the effect of an additional, 25 mm waveguide section designed to model the internal waveguide of the power meter. Adapters without a transition section and a rectangular Winston cone throat aperture and double cone configurations are also studied. Adapters are analyzed in simulation for consistent efficiency across the opening aperture.

Advanced insulated gate bipolar transistor gate drive

DOEpatents

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

2009-08-04

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

Intrinsic bursting of AII amacrine cells underlies oscillations in the rd1 mouse retina.

PubMed

Choi, Hannah; Zhang, Lei; Cembrowski, Mark S; Sabottke, Carl F; Markowitz, Alexander L; Butts, Daniel A; Kath, William L; Singer, Joshua H; Riecke, Hermann

2014-09-15

In many forms of retinal degeneration, photoreceptors die but inner retinal circuits remain intact. In the rd1 mouse, an established model for blinding retinal diseases, spontaneous activity in the coupled network of AII amacrine and ON cone bipolar cells leads to rhythmic bursting of ganglion cells. Since such activity could impair retinal and/or cortical responses to restored photoreceptor function, understanding its nature is important for developing treatments of retinal pathologies. Here we analyzed a compartmental model of the wild-type mouse AII amacrine cell to predict that the cell's intrinsic membrane properties, specifically, interacting fast Na and slow, M-type K conductances, would allow its membrane potential to oscillate when light-evoked excitatory synaptic inputs were withdrawn following photoreceptor degeneration. We tested and confirmed this hypothesis experimentally by recording from AIIs in a slice preparation of rd1 retina. Additionally, recordings from ganglion cells in a whole mount preparation of rd1 retina demonstrated that activity in AIIs was propagated unchanged to elicit bursts of action potentials in ganglion cells. We conclude that oscillations are not an emergent property of a degenerated retinal network. Rather, they arise largely from the intrinsic properties of a single retinal interneuron, the AII amacrine cell. Copyright © 2014 the American Physiological Society.

Cat colour vision: one cone process or several?

PubMed Central

Daw, N. W.; Pearlman, A. L.

1969-01-01

1. Peripheral mechanisms that might contribute to colour vision in the cat have been investigated by recording from single units in the lateral geniculate and optic tract. Evidence is presented that the input to these cells comes from a single class of cones with a single spectral sensitivity. 2. In cats with pupils dilated a background level of 10-30 cd/m2 was sufficient to saturate the rod system for all units. When the rods were saturated, the spectral sensitivity of all units peaked at 556 nm; this was true both for centre and periphery of the receptive field. The spectral sensitivity curve was slightly narrower than the Dartnall nomogram. It could not be shifted by chromatic adaptation with red, green, blue or yellow backgrounds. 3. In the mesopic range (0·1-10 cd/m2), the threshold could be predicted in terms of two mechanisms, a cone mechanism with spectral sensitivity peaking at 556 nm, and a rod mechanism with spectral sensitivity at 500 nm. The mechanisms were separated and their increment threshold curves measured by testing with one colour against a background of another colour. All units had input from both rods and cones. The changeover from rods to cones occurred at the same level of adaptation in both centre and periphery of the receptive field. Threshold for the cones was between 0·04 and 0·25 cd/m2 with the pupil dilated, for a spot covering the centre of the receptive field. 4. None of the results was found to vary between lateral geniculate and optic tract, with layer in the lateral geniculate, or with distance from area centralis in the visual field. 5. The lack of evidence for more than one cone type suggests that colour discrimination in the cat may be a phenomenon of mesopic vision, based on differences in spectral sensitivity of the rods and a single class of cones. PMID:5767891

Endogenous calcium buffering at photoreceptor synaptic terminals in salamander retina

PubMed Central

Van Hook, Matthew J.; Thoreson, Wallace B.

2014-01-01

Calcium operates by several mechanisms to regulate glutamate release at rod and cone synaptic terminals. In addition to serving as the exocytotic trigger, Ca2+ accelerates replenishment of vesicles in cones and triggers Ca2+-induced Ca2+ release (CICR) in rods. Ca2+ thereby amplifies sustained exocytosis, enabling photoreceptor synapses to encode constant and changing light. A complete picture of the role of Ca2+ in regulating synaptic transmission requires an understanding of the endogenous Ca2+ handling mechanisms at the synapse. We therefore used the “added buffer” approach to measure the endogenous Ca2+ binding ratio (κendo) and extrusion rate constant (γ) in synaptic terminals of photoreceptors in retinal slices from tiger salamander. We found that κendo was similar in both cell types - approximately 25 and 50 in rods and cones, respectively. Using measurements of the decay time constants of Ca2+ transients, we found that γ was also similar, with values of approximately 100 s−1 and 160 s−1 in rods and cones, respectively. The measurements of κendo differ considerably from measurements in retinal bipolar cells, another ribbon-bearing class of retinal neurons, but are comparable to similar measurements at other conventional synapses. The values of γ are slower than at other synapses, suggesting that Ca2+ ions linger longer in photoreceptor terminals, supporting sustained exocytosis, CICR, and Ca2+-dependent ribbon replenishment. The mechanisms of endogenous Ca2+ handling in photoreceptors are thus well-suited for supporting tonic neurotransmission. Similarities between rod and cone Ca2+ handling suggest that neither buffering nor extrusion underlie differences in synaptic transmission kinetics. PMID:25049035

A generalized technique for using cones and dihedral angles in attitude determination, revision 1

NASA Technical Reports Server (NTRS)

Werking, R. D.

1973-01-01

Analytic development is presented for a general least squares attitude determination subroutine applicable to spinning satellites. The method is founded on a geometric approach which is completely divorced from considerations relating to particular types and configurations of onboard attitude sensors. Any mix of sensor measurements which can be first transformed (outside the program) to cone or dihedral angle data can be processed. A cone angle is an angle between the spin axis and a known direction line in space; a dihedral angle is an angle between two planes formed by the spin axis and each of two known direction lines. Many different kinds of sensor data can be transformed to these angles, which in turn constitute the actual program inputs, so that the subroutine can be applied without change to a variety of satellite missions. Either a constant or dynamic spin axis model can be handled. The program is also capable of solving for fixed biases in the input angles, in addition to the spin axis attitude solution.

Development of Process Technologies for High-Performance MOS-Based SiC Power Switching Devices

DTIC Science & Technology

2007-08-01

investigated are insulated-gate bipolar transistors ( IGBTs ) in 4H-SiC. The IGBT combines the best aspects of MOS and bipolar power transistors... IGBTs can be thought of as a fusion of a MOSFET and a BJT. The MOSFET provides a high input impedance while the BJT provides conductivity modulation of...region due to conductivity modulation from the forward-biased BJT. The IGBT is structurally identical to a MOSFET, except that the substrate doping

Nonlinear system analysis in bipolar integrated circuits

NASA Astrophysics Data System (ADS)

Fang, T. F.; Whalen, J. J.

1980-01-01

Since analog bipolar integrated circuits (IC's) have become important components in modern communication systems, the study of the Radio Frequency Interference (RFI) effects in bipolar IC amplifiers is an important subject for electromagnetic compatibility (EMC) engineering. The investigation has focused on using the nonlinear circuit analysis program (NCAP) to predict RF demodulation effects in broadband bipolar IC amplifiers. The audio frequency (AF) voltage at the IC amplifier output terminal caused by an amplitude modulated (AM) RF signal at the IC amplifier input terminal was calculated and compared to measured values. Two broadband IC amplifiers were investigated: (1) a cascode circuit using a CA3026 dual differential pair; (2) a unity gain voltage follower circuit using a micro A741 operational amplifier (op amp). Before using NCAP for RFI analysis, the model parameters for each bipolar junction transistor (BJT) in the integrated circuit were determined. Probe measurement techniques, manufacturer's data, and other researcher's data were used to obtain the required NCAP BJT model parameter values. An important contribution included in this effort is a complete set of NCAP BJT model parameters for most of the transistor types used in linear IC's.

ON-retinal bipolar cell survival in RCS rats.

PubMed

Zhang, Chen Xing; Yin, Zheng Qin; Chen, Li-Feng; Weng, Chuang-Huang; Zeng, Yu-Xiao

2010-11-01

In retinitis pigmentosa (RP), the slow and progressive death of inner retinal neurons is thought to be inevitable after the death of photoreceptors. However, even in the advanced stage of RP, all inner retinal neurons are not completely lost. The morphological and electrophysiological modifications in ON-retinal bipolar cells (ON-RBCs) of Royal College of Surgeons (RCS) rats (RCS-ON-RBCs) were investigated to elucidate the mechanisms of survival of RCS-ON-RBCs in RP. Control (CTR) and RCS rats were divided into age groups according to postnatal stage: postnatal day 21 (Pn21d), postnatal day 30 (Pn30d), postnatal day 60 (Pn60d), and postnatal day 90 (Pn90d). Lucifer yellow staining of single ON-RBCs and double-immunofluorescence of the retinal frozen sections were used to detect the morphological modifications and loss of RCS-ON-RBCs in different retinal regions. The whole-cell patch clamping technique was used to record the electrophysiological properties of ON-RBCs. There was a significant loss of RCS-ON-RBCs compared with CTR (p < 0.01) at Pn60d. Loss of the RCS-ON-RBCs differed by region. From Pn60d onwards, the loss was more severe in the peripheral retinal regions (p < 0.01). From Pn21d, the ectopic neurites from the RCS-ON-RBCs reached the outer and inner nuclear layers. At Pn60d, terminal branches of RCS-ON-RBCs axons vanished and ectopic neurites from the RCS-ON-RBCs became entwined. The resting membrane potential, input resistance and outward membrane current amplitude of RCS-ON-RBCs were significantly higher than those of the ON-RBCs of CTR rats at Pn60d (p < 0.05). Our results indicate that more RCS-ON-RBCs survived in the central retinal area near cone clusters, potentially as a result of ectopic neuritis. Meanwhile the surviving RCS-ON-RBCs remained immature and had no normal electrophysiological characteristics.

Psychiatric consultation in the collaborative care model: The "bipolar sieve" effect.

PubMed

Phelps, James R; James, James

2017-08-01

Around the world, psychiatrists are in exceptionally short supply. The majority of mental health treatment is delivered in primary care. In the United States, the Collaborative Care Model (CCM) addresses the shortfall of psychiatrists by providing indirect consultation in primary care. A Cochrane meta-analysis affirms the efficacy this model for depression and anxiety. However, our experience with the CCM suggests that most patients referred for consultation have problems far more complex than simple depression and anxiety. Based on preliminary data, we offer five linked hypotheses: (1) in an efficient collaborative care process, the majority of mental illnesses can be handled by providers who are less expensive and more plentiful than psychiatrists. (2) A majority of the remaining cases will be bipolar disorder variations. Differentiating these from PTSD, the most common alternative or comorbid diagnosis, is challenging and often requires a psychiatrist's input. (3) Psychiatric consultants can teach their primary care colleagues that bipolar diagnoses are estimations based on rigorously assessed probabilities, and that cases fall on a spectrum from unipolar to bipolar. (4) All providers must recognize that when bipolarity is missed, antidepressant prescription often follows. Antidepressants can induce bipolar mixed states, with extreme anxiety and potentially dangerous impulsivity and suicidality. (5) Psychiatrists can help develop clinical approaches in primary care that identify bipolarity and differentiate it from (or establish comorbidity with) PTSD; and psychiatrists can facilitate appropriate treatment, including bipolar-specific psychotherapies as well as use of mood stabilizers. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparison of the Heat Release Rate from the Mass Loss Calorimeter to the Cone Calorimeter for Wood-based Materials

Treesearch

Laura E. Hasburgh; Robert H. White; Mark A. Dietenberger; Charles R. Boardman

2015-01-01

There is a growing demand for material properties to be used as inputs in fi re behavior models designed to address building fire safety. This comparative study evaluates using the mass loss calorimeter as an alternative to the cone calorimeter for obtaining heat release rates of wood-based materials. For this study, a modified mass loss calorimeter utilized an...

Sustained and Transient Contributions to the Rat Dark-Adapted Electroretinogram b-Wave

PubMed Central

Dang, Trung M.; Vingrys, Algis J.; Bui, Bang V.

2013-01-01

The most dominant feature of the electroretinogram, the b-wave, is thought to reflect ON-bipolar cell responses. However, a number of studies suggest that the b-wave is made up of several components. We consider the composition of the rat b-wave by subtracting corneal negative components obtained using intravitreal application of pharmacological agents to remove postreceptoral responses. By analyzing the intensity-response characteristic of the PII across a range of fixed times during and after a light step, we find that the rat isolated PII has 2 components. The first has fast rise and decay characteristics with a low sensitivity to light. GABAc-mediated inhibitory pathways enhance this transient-ON component to manifest increased and deceased sensitivity to light at shorter (<160 ms) and longer times, respectively. The second component has slower temporal characteristics but is more sensitive to light. GABAc-mediated inhibition enhances this sustained-ON component but has little effect on its sensitivity to light. After stimulus offset, both transient and sustained components return to baseline, and a long latency sustained positive component becomes apparent. The light sensitivities of transient-ON and sustained-OFF components are consistent with activity arising from cone ON- and OFF-bipolar cells, whereas the sustained-ON component is likely to arise from rod bipolar cells. PMID:23533706

Amplitude- and rise-time-compensated filters

DOEpatents

Nowlin, Charles H.

1984-01-01

An amplitude-compensated rise-time-compensated filter for a pulse time-of-occurrence (TOOC) measurement system is disclosed. The filter converts an input pulse, having the characteristics of random amplitudes and random, non-zero rise times, to a bipolar output pulse wherein the output pulse has a zero-crossing time that is independent of the rise time and amplitude of the input pulse. The filter differentiates the input pulse, along the linear leading edge of the input pulse, and subtracts therefrom a pulse fractionally proportional to the input pulse. The filter of the present invention can use discrete circuit components and avoids the use of delay lines.

Network Oscillations Drive Correlated Spiking of ON and OFF Ganglion Cells in the rd1 Mouse Model of Retinal Degeneration

PubMed Central

Margolis, David J.; Gartland, Andrew J.; Singer, Joshua H.; Detwiler, Peter B.

2014-01-01

Following photoreceptor degeneration, ON and OFF retinal ganglion cells (RGCs) in the rd-1/rd-1 mouse receive rhythmic synaptic input that elicits bursts of action potentials at ∼10 Hz. To characterize the properties of this activity, RGCs were targeted for paired recording and morphological classification as either ON alpha, OFF alpha or non-alpha RGCs using two-photon imaging. Identified cell types exhibited rhythmic spike activity. Cross-correlation of spike trains recorded simultaneously from pairs of RGCs revealed that activity was correlated more strongly between alpha RGCs than between alpha and non-alpha cell pairs. Bursts of action potentials in alpha RGC pairs of the same type, i.e. two ON or two OFF cells, were in phase, while bursts in dissimilar alpha cell types, i.e. an ON and an OFF RGC, were 180 degrees out of phase. This result is consistent with RGC activity being driven by an input that provides correlated excitation to ON cells and inhibition to OFF cells. A2 amacrine cells were investigated as a candidate cellular mechanism and found to display 10 Hz oscillations in membrane voltage and current that persisted in the presence of antagonists of fast synaptic transmission and were eliminated by tetrodotoxin. Results support the conclusion that the rhythmic RGC activity originates in a presynaptic network of electrically coupled cells including A2s via a Na+-channel dependent mechanism. Network activity drives out of phase oscillations in ON and OFF cone bipolar cells, entraining similar frequency fluctuations in RGC spike activity over an area of retina that migrates with changes in the spatial locus of the cellular oscillator. PMID:24489706

DSCAM-mediated control of dendritic and axonal arbor outgrowth enforces tiling and inhibits synaptic plasticity

PubMed Central

Simmons, Aaron B.; Bloomsburg, Samuel J.; Sukeena, Joshua M.; Miller, Calvin J.; Ortega-Burgos, Yohaniz; Borghuis, Bart G.

2017-01-01

Mature mammalian neurons have a limited ability to extend neurites and make new synaptic connections, but the mechanisms that inhibit such plasticity remain poorly understood. Here, we report that OFF-type retinal bipolar cells in mice are an exception to this rule, as they form new anatomical connections within their tiled dendritic fields well after retinal maturity. The Down syndrome cell-adhesion molecule (Dscam) confines these anatomical rearrangements within the normal tiled fields, as conditional deletion of the gene permits extension of dendrite and axon arbors beyond these borders. Dscam deletion in the mature retina results in expanded dendritic fields and increased cone photoreceptor contacts, demonstrating that DSCAM actively inhibits circuit-level plasticity. Electrophysiological recordings from Dscam−/− OFF bipolar cells showed enlarged visual receptive fields, demonstrating that expanded dendritic territories comprise functional synapses. Our results identify cell-adhesion molecule-mediated inhibition as a regulator of circuit-level neuronal plasticity in the adult retina. PMID:29114051

A Learning Model for L/M Specificity in Ganglion Cells

NASA Technical Reports Server (NTRS)

Ahumada, Albert J.

2016-01-01

An unsupervised learning model for developing LM specific wiring at the ganglion cell level would support the research indicating LM specific wiring at the ganglion cell level (Reid and Shapley, 2002). Removing the contributions to the surround from cells of the same cone type improves the signal-to-noise ratio of the chromatic signals. The unsupervised learning model used is Hebbian associative learning, which strengthens the surround input connections according to the correlation of the output with the input. Since the surround units of the same cone type as the center are redundant with the center, their weights end up disappearing. This process can be thought of as a general mechanism for eliminating unnecessary cells in the nervous system.

Cloning and Immunocytochemical Localization of a Cyclic Nucleotide–Gated Channel α-Subunit to All Cone Photoreceptors in the Mouse Retina

PubMed Central

HIRANO, ARLENE A.; HACK, IRIS; WÄSSLE, HEINZ; DUVOISIN, ROBERT M.

2010-01-01

Cyclic nucleotide–gated channels (CNGC) are ligand-gated ion channels that open and close in response to changes in the intracellular concentration of the second messengers, 3′,5′-cyclic adenosine monophosphate and 3′,5′-cyclic guanosine monophosphate. Most notably, they transduce the chemical signal produced by the absorption of light in photoreceptors into a membrane potential change, which is then transmitted to the ascending visual pathway. CNGCs have also been implicated in the signal transduction of other neurons downstream of the photoreceptors, in particular the ON-bipolar cells, as well as in other areas of the central nervous system. We therefore undertook a search for additional cyclic nucleotide–gated channels expressed in the retina. Following a degenerate reverse transcription polymerase chain reaction approach to amplify low-copy number messages, a cDNA encoding a new splice variant of CNGC α-subunit was isolated from mouse retina and classified as mCNG3. An antiserum raised against the carboxy-terminal sequence identified the retinal cell type expressing mCNG3 as cone photoreceptors. Preembedding immunoelectron microscopy demonstrated its membrane localization in the outer segments, consistent with its role in phototransduction. Double-labeling experiments with cone-specific markers indicated that all cone photoreceptors in the murid retina use the same or a highly conserved cyclic nucleotide–gated channel. Therefore, defects in this channel would be predicted to severely impair photopic vision. PMID:10813773

Progression of Pro23His Retinopathy in a Miniature Swine Model of Retinitis Pigmentosa

PubMed Central

Scott, Patrick A.; de Castro, Juan P. Fernandez; DeMarco, Paul J.; Ross, Jason W.; Njoka, Josephat; Walters, Eric; Prather, Randall S.; McCall, Maureen A.; Kaplan, Henry J.

2017-01-01

Purpose We characterize the progression of retinopathy in Filial 1 (F1) progeny of a transgenic (Tg) founder miniswine exhibiting severe Pro23His (P23H) retinopathy. Methods The F1 TgP23H miniswine progeny were created by crossing TgP23H founder miniswine 53-1 with wild type (WT) inbred miniature swine. Scotopic (rod-driven) and photopic (cone-driven) retinal functions were evaluated in F1 TgP23H and WT littermates using full field electroretinograms (ffERGs) at 1, 2, 3, 6, 9, 12, and 18 months of age, as well as the Tg founder miniswine at 6 years of age. Miniswine were euthanized and their retinas processed for morphologic evaluation at the light and electron microscopic level. Retinal morphology of a 36-month-old Tg miniswine also was examined. Results Wild type littermates reached mature scotopic and photopic retinal function by 3 months, while TgP23H miniswine showed abnormal scotopic ffERGs at the earliest time point, 1 month, and depressed photopic ffERGs after 2 months. Rod and cone photoreceptors (PR) exhibited morphologic abnormalities and dropout from the outer nuclear layer at 1 month, with only a monolayer of cone PR somata remaining after 2 months. The retinas showed progressive neural remodeling of the outer retina that included dendritic retraction of rod bipolar cells and glial seal formation by Müller cells. The TgP23H founder miniswine showed cone PR with relatively intact morphology exclusive to the area centralis. Conclusions The F1 Tg miniswine and the TgP23H founder miniswine exhibit similar retinopathy. Translational Relevance TgP23H miniswine are a useful large-eye model to study pathogenesis and preservation cone PRs in humans with retinitis pigmentosa. PMID:28316877

Foraging performance of two fishes, the threespine stickleback and the Cumaná guppy, under different light backgrounds.

PubMed

Zukoshi, Reo; Savelli, Ilaria; Novales Flamarique, Iñigo

2018-04-01

Many vertebrates have cone photoreceptors that are most sensitive to ultraviolet (UV) light termed UV cones. The ecological functions that these cones contribute to are seldom known though they are suspected of improving foraging and communication in a variety of fishes. In this study, we used several spectral backgrounds to assess the contribution of UV and violet cones, or long wavelength (L) cones, in the foraging performance of juvenile Cumaná guppy, Poecilia reticulata, or marine stickleback, Gasterosteus aculeatus. Regardless of whether the light spectrum contained or not wavelengths below 450 nm (the limiting wavelength for UV cone stimulation), the foraging performance of both species was statistically the same, as judged by the mean distance and angle associated with attacks on prey (Daphnia magna). Our experiments also showed that the foraging performance of sticklebacks when only the double cones (and, almost exclusively, the L cones) were active was similar to that when all cones were functional, demonstrating that the double cone was sufficient for prey detection. This result indicates that foraging potentially relied on an achromatic channel serving prey motion detection, as the two spectral cone types that make up the double cone [maximally sensitive to middle (M) and long (L) wavelengths, respectively] form the input to the achromatic channel in cyprinid fishes and double cones are widely associated with achromatic tasks in other vertebrates including reptiles and birds. Stickleback performance was also substantially better when foraging under a 100% linearly polarized light field than when under an unpolarized light field. Together, our results suggest that in some teleost species UV cones exert visually-mediated ecological functions different from foraging, and furthermore that polarization sensitivity could improve the foraging performance of sticklebacks. Copyright © 2018 Elsevier Ltd. All rights reserved.

Evolution of phototransduction, vertebrate photoreceptors and retina.

PubMed

Lamb, Trevor D

2013-09-01

Evidence is reviewed from a wide range of studies relevant to the evolution of vertebrate photoreceptors and phototransduction, in order to permit the synthesis of a scenario for the major steps that occurred during the evolution of cones, rods and the vertebrate retina. The ancestral opsin originated more than 700 Mya (million years ago) and duplicated to form three branches before cnidarians diverged from our own lineage. During chordate evolution, ciliary opsins (C-opsins) underwent multiple stages of improvement, giving rise to the 'bleaching' opsins that characterise cones and rods. Prior to the '2R' rounds of whole genome duplication near the base of the vertebrate lineage, 'cone' photoreceptors already existed; they possessed a transduction cascade essentially the same as in modern cones, along with two classes of opsin: SWS and LWS (short- and long-wave-sensitive). These cones appear to have made synaptic contact directly onto ganglion cells, in a two-layered retina that resembled the pineal organ of extant non-mammalian vertebrates. Interestingly, those ganglion cells appear to be descendants of microvillar photoreceptor cells. No lens was associated with this two-layered retina, and it is likely to have mediated circadian timing rather than spatial vision. Subsequently, retinal bipolar cells evolved, as variants of ciliary photoreceptors, and greatly increased the computational power of the retina. With the advent of a lens and extraocular muscles, spatial imaging information became available for central processing, and gave rise to vision in vertebrates more than 500 Mya. The '2R' genome duplications permitted the refinement of cascade components suitable for both rods and cones, and also led to the emergence of five visual opsins. The exact timing of the emergence of 'true rods' is not yet clear, but it may not have occurred until after the divergence of jawed and jawless vertebrates. Copyright © 2013 The Author. Published by Elsevier Ltd.. All rights reserved.

Technology-Based Early Warning Systems for Bipolar Disorder: A Conceptual Framework

PubMed Central

Torous, John; Thompson, Wesley

2016-01-01

Recognition and timely action around “warning signs” of illness exacerbation is central to the self-management of bipolar disorder. Due to its heterogeneity and fluctuating course, passive and active mobile technologies have been increasingly evaluated as adjunctive or standalone tools to predict and prevent risk of worsening of course in bipolar disorder. As predictive analytics approaches to big data from mobile health (mHealth) applications and ancillary sensors advance, it is likely that early warning systems will increasingly become available to patients. Such systems could reduce the amount of time spent experiencing symptoms and diminish the immense disability experienced by people with bipolar disorder. However, in addition to the challenges in validating such systems, we argue that early warning systems may not be without harms. Probabilistic warnings may be delivered to individuals who may not be able to interpret the warning, have limited information about what behaviors to change, or are unprepared to or cannot feasibly act due to time or logistic constraints. We propose five essential elements for early warning systems and provide a conceptual framework for designing, incorporating stakeholder input, and validating early warning systems for bipolar disorder with a focus on pragmatic considerations. PMID:27604265

The effects of L-glutamate, AMPA, quisqualate, and kainate on retinal horizontal cells depend on adaptational state: implications for rod-cone interactions.

PubMed

Krizaj, D; Akopian, A; Witkovsky, P

1994-09-01

We studied the responses of isolated and intact luminosity-type horizontal cells (L-HC) in the Xenopus retina to L-glutamate (L-glu) and its analogs. Isolated L-HCs studied with whole-cell patch clamp responded to L-glu, kainate (KA), AMPA, or quisqualate (quis) with inward currents from a holding potential of -60 mV, associated with a conductance increase. The current elicited by KA was relatively large and sustained, whereas AMPA or quis evoked a desensitizing current. Coapplication of quis and KA resulted in a smaller current and conductance change than that evoked by a pulse of either alone at the same concentration. This finding suggests that the L-HC has a single subtype of glutamate receptor that responds to both quis and KA. Prior exposure to dopamine enhanced the KA-evoked current about twofold. In the superfused eyecup we found that L-HC responses to quinoxalinediones (CNQX or DNQX) and to L-glu, KA, AMPA, and quis varied as a function of adaptational state. When driven exclusively by either cones or by rods, CNQX/DNQX hyperpolarized the L-HC and reduced its light response, without altering response kinetics, indicating that both rods and cones communicate with L-HCs at ionotropic glutamatergic synapses. Under mesopic conditions, however, as CNQX or DNQX reduced cone input, the rod input to the L-HC increased up to fivefold in magnitude and had slowed kinetics. The depolarizing response of the L-HC to L-glu, AMPA, or quis was relatively small and transient under photopic conditions, but was much larger and sustained when the eyecup was dark adapted. The D1 dopamine antagonist SCH 23390 potentiated the response to quis. In contrast, responses to KA were largest in light-adapted eyecups, were potentiated by a D1 dopamine agonist, SKF 38393, and were reduced by SCH 23390. We hypothesize that the segregated populations of glutamate receptors in the L-HC opposite cone and rod synaptic endings can be separately modulated to respond differentially to the native transmitter, glutamate. In photopic and mesopic states the dominant cone input tonically inhibits rod to L-HC communication. This inhibition appears to occur at the postsynaptic membrane and may be mediated by second messengers.

Grating acuity at different luminances in wild-type mice and in mice lacking rod or cone function.

PubMed

Schmucker, Christine; Seeliger, Mathias; Humphries, Pete; Biel, Martin; Schaeffel, Frank

2005-01-01

The mouse eye has become an important model in vision research. However, it is not known how visual acuity changes with luminance. Therefore, grating acuity of mice was measured at different luminances in an automated optomotor paradigm. Furthermore, mutant mice lacking either rods (RHO-/- and CNGB1-/-) or cones (CNGA3-/-), or both, were studied to determine the rod and cone contribution to visual acuity. Freely ranging individual mice were automatically tracked at a 25-Hz sampling rate with a self-programmed video system in a large rotating optomotor drum. The drum had a square-wave grating inside with adjustable spatial frequency. The angular speed of the mice with respect to the center of the drum and the angular orientation of the snout-tail body axis were analyzed. In addition, the motor activity of the wild-type mice was recorded at different luminances. The optomotor drum provided reliable data on visual input to the mouse's behavior and was convenient to use, since the experimenter's had only to place the mice individually in a Perspex cylinder. Optomotor grating acuity of the wild-type mice was limited to 0.3 to 0.4 cyc/deg. Maximum optomotor responses were obtained at 0.1 to 0.2 cyc/deg. The importance of visual input declined monotonically with decreasing luminance (30 cd/m2, 100%; 0.1 cd/m2, 76.4%; 0.005 cd/m2, 45.9%; and darkness, -9%). Mice lacking functional rods were able to resolve gratings up to 0.1 cyc/deg at 30 cd/m2. Surprisingly, mice lacking functional cones had an optomotor acuity that was similar to the wild-type. Double-knockout mice without rods and cones had no detectable grating acuity. Because the visual system of the mouse is more responsive at bright luminances, experiments in which visual input is important should be performed in photopic conditions (30 cd/m2 or even more). Apparently, spatial vision is governed by the rod system, which is not saturated in the mesopic or low photopic range. Mice lacking both rods and cones have no detectable grating acuity, indicating that the retinal melanopsin system does not contribute to spatial vision.

Cat colour vision: evidence for more than one cone process

PubMed Central

Daw, N. W.; Pearlman, A. L.

1970-01-01

1. The ability of cats to distinguish colours was investigated at mesopic and photopic levels to test the hypothesis that cats discriminate wavelength by using rods in conjunction with a single type of cone. 2. Cats were trained to distinguish red from cyan, and orange from cyan at the mesopic level. They retained the ability to make this discrimination when the coloured stimuli were placed against a background bright enough to saturate the rods. 3. One cat was also tested after being exposed to a bright white light of 9000 cd/m2 for a period of 5 min, and found able to distinguish red from cyan. 4. These results suggest that cats have more than one type of cone. Subsequent recordings from single units in the lateral geniculate nucleus showed that there are rare opponent colour units in layer B with input from a green-absorbing cone and a blue-absorbing cone. ImagesPlate 1 PMID:5500987

Calculation of stability derivatives for slowly oscillating bodies of revolution at Mach 1.0

NASA Technical Reports Server (NTRS)

Ruo, S. Y.; Liu, D. D.

1971-01-01

A parabolic method for steady transonic flow is extended to bodies of revolution oscillating in a sonic flow field. A Laplace transform technique is employed to derive the dipole solution, and the Adams-Sears iterative technique is used in the stability derivative calculation. A computer program is developed to perform the stability derivative calculation for the slowly oscillating cone and parabolic ogive. Inputs for the program are body geometry thickness ratio, acceleration constant, and pitch axis location. Sample calculations were performed for the parabolic ogive and circular cone and results are compared with those obtained by using other techniques and the available experimental data for circular cones.

ApoER2 Function in the Establishment and Maintenance of Retinal Synaptic Connectivity

PubMed Central

Trotter, Justin H.; Klein, Martin; Jinwal, Umesh K.; Abisambra, Jose F.; Dickey, Chad A.; Tharkur, Jeremy; Masiulis, Irene; Ding, Jindong; Locke, Kirstin G.; Rickman, Catherine Bowes; Birch, David G.; Weeber, Edwin J.; Herz, Joachim

2011-01-01

The cellular and molecular mechanisms responsible for the development of inner retinal circuitry are poorly understood. Reelin and apolipoprotein E (apoE), ligands of apoE receptor 2 (ApoER2), are involved in retinal development and degeneration, respectively. Here we describe the function of ApoER2 in the developing and adult retina. ApoER2 expression was highest during postnatal inner retinal synaptic development and was considerably lower in the mature retina. Both during development and in the adult ApoER2 was expressed by A-II amacrine cells. ApoER2 knockout (KO) mice had rod bipolar morphogenic defects, altered A-II amacrine dendritic development, and impaired rod-driven retinal responses. The presence of an intact ApoER2 NPxY motif, necessary for binding disabled-1 (Dab1) and transducing the Reelin signal, was also necessary for development of the rod bipolar pathway while the alternatively-spliced exon19 was not. Mice deficient in another Reelin receptor, very low-density lipoprotein receptor (VLDLR), had normal rod bipolar morphology but altered A-II amacrine dendritic development. VLDLR KO mice also had reductions in oscillatory potentials and delayed synaptic response intervals. Interestingly, age-related reductions in rod and cone function were observed in both ApoER2 and VLDLR KOs. These results support a pivotal role for ApoER2 in the establishment and maintenance of normal retinal synaptic connectivity. PMID:21976526

Curing Color Blindness—Mice and Nonhuman Primates

PubMed Central

Neitz, Maureen; Neitz, Jay

2014-01-01

It has been possible to use viral-mediated gene therapy to transform dichromatic (red-green color-blind) primates to trichromatic. Even though the third cone type was added after the end of developmental critical periods, treated animals acquired red-green color vision. What happened in the treated animals may represent a recapitulation of the evolution of trichromacy, which seems to have evolved with the acquisition of a third cone type without the need for subsequent modification to the circuitry. Some transgenic mice in which a third cone type was added also acquired trichromacy. However, compared with treated primates, red-green color vision in mice is poor, indicating large differences between mice and monkeys in their ability to take advantage of the new input. These results have implications for understanding the limits and opportunities for using gene therapy to treat vision disorders caused by defects in cone function. PMID:25147187

Curing color blindness--mice and nonhuman primates.

PubMed

Neitz, Maureen; Neitz, Jay

2014-08-21

It has been possible to use viral-mediated gene therapy to transform dichromatic (red-green color-blind) primates to trichromatic. Even though the third cone type was added after the end of developmental critical periods, treated animals acquired red-green color vision. What happened in the treated animals may represent a recapitulation of the evolution of trichromacy, which seems to have evolved with the acquisition of a third cone type without the need for subsequent modification to the circuitry. Some transgenic mice in which a third cone type was added also acquired trichromacy. However, compared with treated primates, red-green color vision in mice is poor, indicating large differences between mice and monkeys in their ability to take advantage of the new input. These results have implications for understanding the limits and opportunities for using gene therapy to treat vision disorders caused by defects in cone function. Copyright © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.

Melanopsin changes in neonatal albino rat independent of rods and cones.

PubMed

Hannibal, Jens; Georg, Birgitte; Fahrenkrug, Jan

2007-01-08

Intrinsically photosensitive retinal ganglion cells employ the photopigment melanopsin and provide light information to brain areas responsible for the regulation of circadian rhythms. The expression of melanopsin is regulated by environmental illumination, but it remains to be clarified whether the rods and cones are involved. Here, we examined the influence of 5 days of constant light and dark conditions on melanopsin mRNA and protein expression in newborn albino rats, in which functional rods and cones have not yet been developed. We found that the melanopsin mRNA level was unaffected, whereas the melanopsin protein level was more than two-fold higher in the darkness-adapted group than in pups raised in constant light. In pups raised during 12 : 12 h light/dark cycles, the melanopsin protein level was significantly higher during the day than at night. Our findings indicate that melanopsin protein changes are independent of input from the rods and cones.

Rapid synaptic vesicle endocytosis in cone photoreceptors of salamander retina

PubMed Central

Van Hook, Matthew J.; Thoreson, Wallace B.

2013-01-01

Following synaptic vesicle exocytosis, neurons retrieve the fused membrane by a process of endocytosis in order to provide a supply of vesicles for subsequent release and maintain the presynaptic active zone. Rod and cone photoreceptors use a specialized structure called the synaptic ribbon that enables them to sustain high rates of neurotransmitter release. They must also employ mechanisms of synaptic vesicle endocytosis capable of keeping up with release. While much is known about endocytosis at another retinal ribbon synapse, that of the goldfish Mb1 bipolar cell, less is known about endocytosis in photoreceptors. We used capacitance recording techniques to measure vesicle membrane fusion and retrieval in photoreceptors from salamander retinal slices. We found that application of brief depolarizing steps (<100 ms) to cones evoked exocytosis followed by rapid endocytosis with a time constant ~250 ms. In some cases, the capacitance trace overshot the baseline, indicating excess endocytosis. Calcium had no effect on the time constant, but enhanced excess endocytosis resulting in a faster rate of membrane retrieval. Surprisingly, endocytosis was unaffected by blockers of dynamin, suggesting that cone endocytosis is dynamin-independent. This contrasts with synaptic vesicle endocytosis in rods, which was inhibited by the dynamin inhibitor dynasore and GTPγS introduced through the patch pipette, suggesting that the two photoreceptor types employ distinct pathways for vesicle retrieval. The fast kinetics of synaptic vesicle endocytosis in photoreceptors likely enables these cells to maintain a high rate of transmitter release, allowing them to faithfully signal changes in illumination to second-order neurons. PMID:23238726

Robust Controller Design: A Bounded-Input-Bounded-Output Worst-Case Approach

DTIC Science & Technology

1992-03-01

show that 2 implies 1, suppose 1 does not hold, i.e., that p(M) > 1. The Perron - Frobenius theory for nonnegative matrices states that p(M) is itself an...Pz denote the positive cones inside X, Z consisting of elements with nonnegative pointwise components. Define the operator .4 : X -* Z, decomposed...topology.) The dual cone P! again consists of the nonnegative elements in Z*. The Lagrangian can be defined as L(x,z ’) {< x,c" > + < Ax - b,z

Layered recognition networks that pre-process, classify, and describe

NASA Technical Reports Server (NTRS)

Uhr, L.

1971-01-01

A brief overview is presented of six types of pattern recognition programs that: (1) preprocess, then characterize; (2) preprocess and characterize together; (3) preprocess and characterize into a recognition cone; (4) describe as well as name; (5) compose interrelated descriptions; and (6) converse. A computer program (of types 3 through 6) is presented that transforms and characterizes the input scene through the successive layers of a recognition cone, and then engages in a stylized conversation to describe the scene.

Spectral and spatial selectivity of luminance vision in reef fish.

PubMed

Siebeck, Ulrike E; Wallis, Guy Michael; Litherland, Lenore; Ganeshina, Olga; Vorobyev, Misha

2014-01-01

Luminance vision has high spatial resolution and is used for form vision and texture discrimination. In humans, birds and bees luminance channel is spectrally selective-it depends on the signals of the long-wavelength sensitive photoreceptors (bees) or on the sum of long- and middle-wavelength sensitive cones (humans), but not on the signal of the short-wavelength sensitive (blue) photoreceptors. The reasons of such selectivity are not fully understood. The aim of this study is to reveal the inputs of cone signals to high resolution luminance vision in reef fish. Sixteen freshly caught damselfish, Pomacentrus amboinensis, were trained to discriminate stimuli differing either in their color or in their fine patterns (stripes vs. cheques). Three colors ("bright green", "dark green" and "blue") were used to create two sets of color and two sets of pattern stimuli. The "bright green" and "dark green" were similar in their chromatic properties for fish, but differed in their lightness; the "dark green" differed from "blue" in the signal for the blue cone, but yielded similar signals in the long-wavelength and middle-wavelength cones. Fish easily learned to discriminate "bright green" from "dark green" and "dark green" from "blue" stimuli. Fish also could discriminate the fine patterns created from "dark green" and "bright green". However, fish failed to discriminate fine patterns created from "blue" and "dark green" colors, i.e., the colors that provided contrast for the blue-sensitive photoreceptor, but not for the long-wavelength sensitive one. High resolution luminance vision in damselfish, Pomacentrus amboinensis, does not have input from the blue-sensitive cone, which may indicate that the spectral selectivity of luminance channel is a general feature of visual processing in both aquatic and terrestrial animals.

Evaluation of force generation mechanisms in natural, passive hydraulic actuators

NASA Astrophysics Data System (ADS)

Le Duigou, A.; Castro, M.

2016-01-01

Pine cones are well known natural actuators that can move their scales upon humidity gradient. The mechanism manifests itself through a displacement easily observable by the naked eye, but coupled with stress generation. In ancient Egypt, wooden wedges were used to break soft blocks of stone by the generated swelling stress. The purpose of the present study is to evaluate the ability of pine cone scales to generate forces while being wetted. In our experiments, a blocking force of around 3N is measured depending on the position on the pine cone where the scales are extracted. A fairly good agreement is obtained when theoretical results based on bimetallic strip systems are compared with experimental data, even if overestimation is observed arising from the input data considered for dry tissues. Inspired by a simplified pine cone microstructure, a biocomposite analogue is manufactured and tested. Although an adequate blocking force can be generated, it has a lower value compared to natural pine cones which benefit from optimized swelling tissue content and interfacial bond strength between them. This study provides new insights to understand the generation of force by pine cones as well as to develop novel biocomposite functionalities.

The Effect of PKCα on the Light Response of Rod Bipolar Cells in the Mouse Retina

PubMed Central

Xiong, Wei-Hong; Pang, Ji-Jie; Pennesi, Mark E.; Duvoisin, Robert M.; Wu, Samuel M.; Morgans, Catherine W.

2015-01-01

Purpose Protein kinase C α (PKCα) is abundantly expressed in rod bipolar cells (RBCs) in the retina, yet the physiological function of PKCα in these cells is not well understood. To elucidate the role of PKCα in visual processing in the eye, we examined the effect of genetic deletion of PKCα on the ERG and on RBC light responses in the mouse. Methods Immunofluorescent labeling was performed on wild-type (WT), TRPM1 knockout, and PKCα knockout (PKC-KO) retina. Scotopic and photopic ERGs were recorded from WT and PKC-KO mice. Light responses of RBCs were measured using whole-cell recordings in retinal slices from WT and PKC-KO mice. Results Protein kinase C alpha expression in RBCs is correlated with the activity state of the cell. Rod bipolar cells dendrites are a major site of PKCα phosphorylation. Electroretinogram recordings indicated that loss of PKCα affects the scotopic b-wave, including a larger peak amplitude, longer implicit time, and broader width of the b-wave. There were no differences in the ERG a- or c-wave between PKCα KO and WT mice, indicating no measurable effect of PKCα in photoreceptors or the RPE. The photopic ERG was unaffected consistent with the lack of detectable PKCα in cone bipolar cells. Whole-cell recordings from RBCs in PKC-KO retinal slices revealed that, compared with WT, RBC light responses in the PKC-KO retina are delayed and of longer duration. Conclusions Protein kinase C alpha plays an important modulatory role in RBCs, regulating both the peak amplitude and temporal properties of the RBC light response in the rod visual pathway. PMID:26230760

Simple tunnel diode circuit for accurate zero crossing timing

NASA Technical Reports Server (NTRS)

Metz, A. J.

1969-01-01

Tunnel diode circuit, capable of timing the zero crossing point of bipolar pulses, provides effective design for a fast crossing detector. It combines a nonlinear load line with the diode to detect the zero crossing of a wide range of input waveshapes.

Waveshaping electronic circuit

NASA Technical Reports Server (NTRS)

Harper, T. P.

1971-01-01

Circuit provides output signal with sinusoidal function in response to bipolar transition of input signal. Instantaneous transition shapes into linear rate of change and linear rate of change shapes into sinusoidal rate of change. Circuit contains only active components; therefore, compatibility with integrated circuit techniques is assured.

A unified classification model for modeling of seismic liquefaction potential of soil based on CPT

PubMed Central

Samui, Pijush; Hariharan, R.

2014-01-01

The evaluation of liquefaction potential of soil due to an earthquake is an important step in geosciences. This article examines the capability of Minimax Probability Machine (MPM) for the prediction of seismic liquefaction potential of soil based on the Cone Penetration Test (CPT) data. The dataset has been taken from Chi–Chi earthquake. MPM is developed based on the use of hyperplanes. It has been adopted as a classification tool. This article uses two models (MODEL I and MODEL II). MODEL I employs Cone Resistance (qc) and Cyclic Stress Ratio (CSR) as input variables. qc and Peak Ground Acceleration (PGA) have been taken as inputs for MODEL II. The developed MPM gives 100% accuracy. The results show that the developed MPM can predict liquefaction potential of soil based on qc and PGA. PMID:26199749

A unified classification model for modeling of seismic liquefaction potential of soil based on CPT.

PubMed

Samui, Pijush; Hariharan, R

2015-07-01

The evaluation of liquefaction potential of soil due to an earthquake is an important step in geosciences. This article examines the capability of Minimax Probability Machine (MPM) for the prediction of seismic liquefaction potential of soil based on the Cone Penetration Test (CPT) data. The dataset has been taken from Chi-Chi earthquake. MPM is developed based on the use of hyperplanes. It has been adopted as a classification tool. This article uses two models (MODEL I and MODEL II). MODEL I employs Cone Resistance (q c) and Cyclic Stress Ratio (CSR) as input variables. q c and Peak Ground Acceleration (PGA) have been taken as inputs for MODEL II. The developed MPM gives 100% accuracy. The results show that the developed MPM can predict liquefaction potential of soil based on q c and PGA.

Differential distribution of fibroblast growth factor receptors (FGFRs) on foveal cones: FGFR-4 is an early marker of cone photoreceptors.

PubMed

Cornish, Elisa E; Natoli, Riccardo C; Hendrickson, Anita; Provis, Jan M

2004-01-08

Relatively little is known of the expression and distribution of FGF receptors (FGFR) in the primate retina. We investigated expression of FGFRs in developing and adult Macaca monkey retina, paying particular attention to the cone rich, macular region. One fetal human retina was used for diagnostic PCR using primers designed for FGFR1, FGFR2, FGFR3, FGFR4, and FGFR like-protein 1 (FGFrl1) and for probe design to FGFR3, FGFR4, and FGFrl1. Rat cDNA was used to synthesize probes for FGFR1 and FGFR2 with 90% and 93% homology to human, respectively. Paraffin sections of retina from macaque fetuses sacrificed at fetal days (Fd) 64, 73, 85, 105, 115, 120, and 165, and postnatal ages 2.5 and 11 years were used to detect FGF receptors by immunohistochemistry and in situ hybridization. PCR showed each of the FGF receptors are expressed in fetal human retina. In situ hybridization indicated that mRNA for each receptor is expressed in all retinal cell layers during development, but most intensely in the ganglion cell layer (GCL). FGFR2 mRNA is reduced in the adult inner (INL) and outer (ONL) nuclear layers, while FGFrl1 mRNA is virtually absent from the adult ONL. FGFR4 mRNA is particularly intense in fetal and adult cone photoreceptors. Immunoreactivity to FGFR1-FGFR4 was detected in the interphotoreceptor matrix in what appeared to be RPE microvilli associated with developing photoreceptor outer segments, and generally is high in the GCL and low in the INL. Different patterns of FGFR3 and FGFR4 immunoreactivities in the outer plexiform layer (OPL) suggest localization of FGFR3 to horizontal cell processes, with FGFR4 being expressed by both horizontal and bipolar cell processes. FGFR1, FGFR3, and FGFR4 immunoreactivities are present in the inner segments and somata of adult cones. The pedicles of developing and adult cones are FGFR1 and FGFR3 immunoreactive, and the basal, synaptic region is FGFR4 immunoreactive. FGFR4 labels cones almost in their entirety from early in development and is not detected in rods. The fibers of Henle are intensely FGFR4 immunoreactive in adult cones. The results show high levels of FGF receptor expression in developing and adult retina. Differential distribution of FGF receptors across developing and adult photoreceptors suggests specific roles for FGF signalling in development and maintenance of photoreceptors, particularly the specialized cones of the fovea.

The Reconstruction Toolkit (RTK), an open-source cone-beam CT reconstruction toolkit based on the Insight Toolkit (ITK)

NASA Astrophysics Data System (ADS)

Rit, S.; Vila Oliva, M.; Brousmiche, S.; Labarbe, R.; Sarrut, D.; Sharp, G. C.

2014-03-01

We propose the Reconstruction Toolkit (RTK, http://www.openrtk.org), an open-source toolkit for fast cone-beam CT reconstruction, based on the Insight Toolkit (ITK) and using GPU code extracted from Plastimatch. RTK is developed by an open consortium (see affiliations) under the non-contaminating Apache 2.0 license. The quality of the platform is daily checked with regression tests in partnership with Kitware, the company supporting ITK. Several features are already available: Elekta, Varian and IBA inputs, multi-threaded Feldkamp-David-Kress reconstruction on CPU and GPU, Parker short scan weighting, multi-threaded CPU and GPU forward projectors, etc. Each feature is either accessible through command line tools or C++ classes that can be included in independent software. A MIDAS community has been opened to share CatPhan datasets of several vendors (Elekta, Varian and IBA). RTK will be used in the upcoming cone-beam CT scanner developed by IBA for proton therapy rooms. Many features are under development: new input format support, iterative reconstruction, hybrid Monte Carlo / deterministic CBCT simulation, etc. RTK has been built to freely share tomographic reconstruction developments between researchers and is open for new contributions.

The diagnostic usefulness of the negative electroretinogram.

PubMed

Fuente García, C; González-López, J J; Muñoz-Negrete, F J; Rebolleda, G

2018-03-01

The definition of the negative response of the full field electroretinogram is the presence of a b-wave with less amplitude than the a-wave (b/a ratio<1) in the combined response of cones and rods. The presence of this pattern reflects an alteration in the bipolar cells, the Müller cells, or in the transmission of the stimulus from the photoreceptors to the bipolar cells, with preserved photoreceptor function. This finding can be seen bilaterally and symmetrically in different hereditary conditions, such as congenital stationary night blindness, juvenile X-linked retinoschisis, and Duchenne and Becker muscular dystrophies. On the other hand, it can also be found unilaterally (or asymmetrically) in acquired pathologies, such as some types of immuno-mediated retinitis (Birdshot retinochoroiditis), autoimmune retinopathies, cancer/melanoma associated retinopathy, or retinal toxicity. The objective of this review is to summarise the characteristics of the pathologies in which this finding can be observed, in order to highlight its usefulness in the differential diagnosis of retinal conditions. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

Mapping Kainate Activation of Inner Neurons in the Rat Retina

PubMed Central

Nivison-Smith, Lisa; Sun, Daniel; Fletcher, Erica L.; Marc, Robert E.; Kalloniatis, Michael

2014-01-01

Kainate receptors mediate fast, excitatory synaptic transmission for a range of inner neurons in the mammalian retina. However, allocation of functional kainate receptors to known cell types and their sensitivity remains unresolved. Using the cation channel probe 1-amino-4-guanidobutane agmatine (AGB), we investigated kainate sensitivity of neurochemically identified cell populations within the structurally intact rat retina. Most inner retinal neuron populations responded to kainate in a concentration-dependent manner. OFF cone bipolar cells demonstrated the highest sensitivity of all inner neurons to kainate. Immunocytochemical localization of AGB and macromolecular markers confirmed that type 2 bipolar cells were part of this kainate-sensitive population. The majority of amacrine (ACs) and ganglion cells (GCs) showed kainate responses with different sensitivities between major neurochemical classes (γ-aminobutyric acid [GABA]/glycine ACs > glycine ACs > GABA ACs; glutamate [Glu]/weakly GABA GCs > Glu GCs). Conventional and displaced cholinergic ACs were highly responsive to kainate, whereas dopaminergic ACs do not appear to express functional kainate receptors. These findings further contribute to our understanding of neuronal networks in complex multicellular tissues. PMID:23348566

A nonlinear macromodel of the bipolar integrated circuit operational amplifier for electromagnetic interference analysis

NASA Astrophysics Data System (ADS)

Chen, G. K. C.

1981-06-01

A nonlinear macromodel for the bipolar transistor integrated circuit operational amplifier is derived from the macromodel proposed by Boyle. The nonlinear macromodel contains only two nonlinear transistors in the input stage in a differential amplifier configuration. Parasitic capacitance effects are represented by capacitors placed at the collectors and emitters of the input transistors. The nonlinear macromodel is effective in predicting the second order intermodulation effect of operational amplifiers in a unity gain buffer amplifier configuration. The nonlinear analysis computer program NCAP is used for the analysis. Accurate prediction of demodulation of amplitude modulated RF signals with RF carrier frequencies in the 0.05 to 100 MHz range is achieved. The macromodel predicted results, presented in the form of second order nonlinear transfer function, come to within 6 dB of the full model predictions for the 741 type of operational amplifiers for values of the second order transfer function greater than -40 dB.

Support vector machines-based modelling of seismic liquefaction potential

NASA Astrophysics Data System (ADS)

Pal, Mahesh

2006-08-01

This paper investigates the potential of support vector machines (SVM)-based classification approach to assess the liquefaction potential from actual standard penetration test (SPT) and cone penetration test (CPT) field data. SVMs are based on statistical learning theory and found to work well in comparison to neural networks in several other applications. Both CPT and SPT field data sets is used with SVMs for predicting the occurrence and non-occurrence of liquefaction based on different input parameter combination. With SPT and CPT test data sets, highest accuracy of 96 and 97%, respectively, was achieved with SVMs. This suggests that SVMs can effectively be used to model the complex relationship between different soil parameter and the liquefaction potential. Several other combinations of input variable were used to assess the influence of different input parameters on liquefaction potential. Proposed approach suggest that neither normalized cone resistance value with CPT data nor the calculation of standardized SPT value is required with SPT data. Further, SVMs required few user-defined parameters and provide better performance in comparison to neural network approach.

Dopamine D1 receptor activation contributes to light-adapted changes in retinal inhibition to rod bipolar cells.

PubMed

Flood, Michael Daniel; Moore-Dotson, Johnnie M; Eggers, Erika D

2018-05-30

Dopamine modulation of retinal signaling has been shown to be an important part of retinal adaptation to increased background light levels but the role of dopamine modulation of retinal inhibition is not clear. We previously showed that light adaptation causes a large reduction in inhibition to rod bipolar cells, potentially to match the decrease in excitation after rod saturation. In this study we determined how dopamine D1 receptors in the inner retina contribute to this modulation. We found that D1 receptor activation significantly decreased the magnitude of inhibitory light responses from rod bipolar cells, while D1 receptor blockade during light adaptation partially prevented this decline. To determine what mechanisms were involved in the modulation of inhibitory light responses, we measured the effect of D1 receptor activation on spontaneous currents and currents evoked from electrically stimulating amacrine cell inputs to rod bipolar cells. D1 receptor activation decreased the frequency of spontaneous inhibition with no change in event amplitudes, suggesting a presynaptic change in amacrine cell activity in agreement with previous reports that rod bipolar cells lack D1 receptors. Additionally, we found that D1 receptor activation reduced the amplitude of electrically-evoked responses, showing that D1 receptors can modulate amacrine cells directly. Our results suggest that D1 receptor activation can replicate a large portion, but not all of the effects of light adaptation, likely by modulating release from amacrine cells onto rod bipolar cells.

Ultrastructural observations of the larva of Tubiluchus corallicola (Priapulida)

NASA Astrophysics Data System (ADS)

Higgins, R. P.; Storch, V.

1989-03-01

Larvae of Tubiluchus corallicola van der Land 1968 were investigated by scanning and transmission electron microscopy. The scalids are sensory organs, each has a bipolar receptor cell with a single apical cilium similar to the scalid in the adult. Muscle cells of the larva are more differentiated than previously reported for other Priapulida; the larval arrangement of circular and longitudinal musculature differs from that of the adult, and a diaphragm is reported for the first time in Priapulida. The diaphragm may function in hydrostatic control of eversion and inversion of the introvert and mouth cone. The functional morphology of these two structures is discussed and contrasted with the Kinorhyncha.

Night blindness and abnormal cone electroretinogram ON responses in patients with mutations in the GRM6 gene encoding mGluR6

PubMed Central

Dryja, Thaddeus P.; McGee, Terri L.; Berson, Eliot L.; Fishman, Gerald A.; Sandberg, Michael A.; Alexander, Kenneth R.; Derlacki, Deborah J.; Rajagopalan, Aruna S.

2005-01-01

We report three unrelated patients with mutations in the GRM6 gene that normally encodes the glutamate receptor mGluR6. This neurotransmitter receptor has been shown previously to be present only in the synapses of the ON bipolar cell dendrites, and it mediates synaptic transmission from rod and cone photoreceptors to this type of second-order neuron. Despite the synaptic defect, best visual acuities were normal or only moderately reduced (20/15 to 20/40). The patients were night blind from an early age, and when maximally dark-adapted, they could perceive lights only with an intensity equal to or slightly dimmer than that normally detected by the cone system (i.e., 2-3 log units above normal). Electroretinograms (ERGs) in response to single brief flashes of light had clearly detectable a-waves, which are derived from photoreceptors, and greatly reduced b-waves, which are derived from the second-order inner retinal neurons. ERGs in response to sawtooth flickering light indicated a markedly reduced ON response and a nearly normal OFF response. There was no subjective delay in the perception of suddenly appearing white vs. black objects on a gray background. These patients exemplify a previously unrecognized, autosomal recessive form of congenital night blindness associated with a negative ERG waveform. PMID:15781871

Aging of human short-wave cone pathways

PubMed Central

Shinomori, Keizo; Werner, John S.

2012-01-01

The retinal image is sampled concurrently, and largely independently, by three physiologically and anatomically distinct pathways, each with separate ON and OFF subdivisions. The retinal circuitry giving rise to an ON pathway receiving input from the short-wave-sensitive (S) cones is well understood, but the S-cone OFF circuitry is more controversial. Here, we characterize the temporal properties of putative S-cone ON and OFF pathways in younger and older observers by measuring thresholds for stimuli that produce increases or decreases in S-cone stimulation, while the middle- and long-wave-sensitive cones are unmodulated. We characterize the data in terms of an impulse response function, the theoretical response to a flash of infinitely short duration, from which the response to any temporally varying stimulus may be predicted. Results show that the S-cone response to increments is faster than to decrements, but this difference is significantly greater for older individuals. The impulse response function amplitudes for increment and decrement responses are highly correlated across individuals, whereas the timing is not. This strongly suggests that the amplitude is controlled by neural circuitry that is common to S-cone ON and OFF responses (photoreceptors), whereas the timing is controlled by separate postreceptoral pathways. The slower response of the putative OFF pathway is ascribed to different retinal circuitry, possibly attributable to a sign-inverting amacrine cell not present in the ON pathway. It is significant that this pathway is affected selectively in the elderly by becoming slower, whereas the temporal properties of the S-cone ON response are stable across the life span of an individual. PMID:22847416

The elementary representation of spatial and color vision in the human retina.

PubMed

Sabesan, Ramkumar; Schmidt, Brian P; Tuten, William S; Roorda, Austin

2016-09-01

The retina is the most accessible element of the central nervous system for linking behavior to the activity of isolated neurons. We unraveled behavior at the elementary level of single input units-the visual sensation generated by stimulating individual long (L), middle (M), and short (S) wavelength-sensitive cones with light. Spectrally identified cones near the fovea of human observers were targeted with small spots of light, and the type, proportion, and repeatability of the elicited sensations were recorded. Two distinct populations of cones were observed: a smaller group predominantly associated with signaling chromatic sensations and a second, more numerous population linked to achromatic percepts. Red and green sensations were mainly driven by L- and M-cones, respectively, although both cone types elicited achromatic percepts. Sensations generated by cones were rarely stochastic; rather, they were consistent over many months and were dominated by one specific perceptual category. Cones lying in the midst of a pure spectrally opponent neighborhood, an arrangement purported to be most efficient in producing chromatic signals in downstream neurons, were no more likely to signal chromatic percepts. Overall, the results are consistent with the idea that the nervous system encodes high-resolution achromatic information and lower-resolution color signals in separate pathways that emerge as early as the first synapse. The lower proportion of cones eliciting color sensations may reflect a lack of evolutionary pressure for the chromatic system to be as fine-grained as the high-acuity achromatic system.

The elementary representation of spatial and color vision in the human retina

PubMed Central

Sabesan, Ramkumar; Schmidt, Brian P.; Tuten, William S.; Roorda, Austin

2016-01-01

The retina is the most accessible element of the central nervous system for linking behavior to the activity of isolated neurons. We unraveled behavior at the elementary level of single input units—the visual sensation generated by stimulating individual long (L), middle (M), and short (S) wavelength–sensitive cones with light. Spectrally identified cones near the fovea of human observers were targeted with small spots of light, and the type, proportion, and repeatability of the elicited sensations were recorded. Two distinct populations of cones were observed: a smaller group predominantly associated with signaling chromatic sensations and a second, more numerous population linked to achromatic percepts. Red and green sensations were mainly driven by L- and M-cones, respectively, although both cone types elicited achromatic percepts. Sensations generated by cones were rarely stochastic; rather, they were consistent over many months and were dominated by one specific perceptual category. Cones lying in the midst of a pure spectrally opponent neighborhood, an arrangement purported to be most efficient in producing chromatic signals in downstream neurons, were no more likely to signal chromatic percepts. Overall, the results are consistent with the idea that the nervous system encodes high-resolution achromatic information and lower-resolution color signals in separate pathways that emerge as early as the first synapse. The lower proportion of cones eliciting color sensations may reflect a lack of evolutionary pressure for the chromatic system to be as fine-grained as the high-acuity achromatic system. PMID:27652339

Retinal Remodeling in the Tg P347L Rabbit, a Large-Eye Model of Retinal Degeneration

PubMed Central

Jones, Bryan William; Kondo, Mineo; Terasaki, Hiroko; Watt, Carl Brock; Rapp, Kevin; Anderson, James; Lin, Yanhua; Shaw, Marguerite Victoria; Yang, Jia-Hui; Marc, Robert Edward

2013-01-01

Retinitis pigmentosa (RP) is an inherited blinding disease characterized by progressive loss of retinal photo-receptors. There are numerous rodent models of retinal degeneration, but most are poor platforms for interventions that will translate into clinical practice. The rabbit possesses a number of desirable qualities for a model of retinal disease including a large eye and an existing and substantial knowledge base in retinal circuitry, anatomy, and ophthalmology. We have analyzed degeneration, remodeling, and reprogramming in a rabbit model of retinal degeneration, expressing a rhodopsin proline 347 to leucine transgene in a TgP347L rabbit as a powerful model to study the pathophysiology and treatment of retinal degeneration. We show that disease progression in the TgP347L rabbit closely tracks human cone-sparing RP, including the cone-associated preservation of bipolar cell signaling and triggering of reprogramming. The relatively fast disease progression makes the TgP347L rabbit an excellent model for gene therapy, cell biological intervention, progenitor cell transplantation, surgical interventions, and bionic prosthetic studies. PMID:21681749

Miniature electrometer preamplifier effectively compensates for input capacitance

NASA Technical Reports Server (NTRS)

Burrous, C. N.; Deboo, G. J.

1966-01-01

Negative capacitance preamplifier using a dual MOS /Metal Oxide Silicon/ transistor in conjunction with bipolar transistors is used with intracellular microelectrodes in recording bioelectric potentials. Applications would include use as a pickup plate video amplifier in storage tube tests and for pH and ionization chamber measurements.

Neurobiological hypothesis of color appearance and hue perception

PubMed Central

Schmidt, Brian P.; Neitz, Maureen; Neitz, Jay

2014-01-01

DeValois and DeValois (1993) showed that to explain hue appearance, S-cone signals have to be combined with M vs. L opponent signals in two different ways to produce red-green and yellow-blue axes respectively. Recently, it has been shown that color appearance is normal for individuals with genetic mutations that block S-cone input to blue-on ganglion cells. This is inconsistent with the DeValois hypothesis in which S-opponent konio-geniculate signals are combined with L−M signals at a 3rd processing stage in cortex. Instead, here we show that color appearance, including individual differences never explained before, are predicted by a model in which S-cone signals are combined with L vs. M signals in the outer retina. PMID:24695170

A parallel input composite transimpedance amplifier.

PubMed

Kim, D J; Kim, C

2018-01-01

A new approach to high performance current to voltage preamplifier design is presented. The design using multiple operational amplifiers (op-amps) has a parasitic capacitance compensation network and a composite amplifier topology for fast, precision, and low noise performance. The input stage consisting of a parallel linked JFET op-amps and a high-speed bipolar junction transistor (BJT) gain stage driving the output in the composite amplifier topology, cooperating with the capacitance compensation feedback network, ensures wide bandwidth stability in the presence of input capacitance above 40 nF. The design is ideal for any two-probe measurement, including high impedance transport and scanning tunneling microscopy measurements.

A parallel input composite transimpedance amplifier

NASA Astrophysics Data System (ADS)

Kim, D. J.; Kim, C.

2018-01-01

A new approach to high performance current to voltage preamplifier design is presented. The design using multiple operational amplifiers (op-amps) has a parasitic capacitance compensation network and a composite amplifier topology for fast, precision, and low noise performance. The input stage consisting of a parallel linked JFET op-amps and a high-speed bipolar junction transistor (BJT) gain stage driving the output in the composite amplifier topology, cooperating with the capacitance compensation feedback network, ensures wide bandwidth stability in the presence of input capacitance above 40 nF. The design is ideal for any two-probe measurement, including high impedance transport and scanning tunneling microscopy measurements.

Synaptic Ribbon Active Zones in Cone Photoreceptors Operate Independently from One Another

PubMed Central

Grassmeyer, Justin J.; Thoreson, Wallace B.

2017-01-01

Cone photoreceptors depolarize in darkness to release glutamate-laden synaptic vesicles. Essential to release is the synaptic ribbon, a structure that helps organize active zones by clustering vesicles near proteins that mediate exocytosis, including voltage-gated Ca2+ channels. Cone terminals have many ribbon-style active zones at which second-order neurons receive input. We asked whether there are functionally significant differences in local Ca2+ influx among ribbons in individual cones. We combined confocal Ca2+ imaging to measure Ca2+ influx at individual ribbons and patch clamp recordings to record whole-cell ICa in salamander cones. We found that the voltage for half-maximal activation (V50) of whole cell ICa in cones averaged −38.1 mV ± 3.05 mV (standard deviation [SD]), close to the cone membrane potential in darkness of ca. −40 mV. Ca2+ signals at individual ribbons varied in amplitude from one another and showed greater variability in V50 values than whole-cell ICa, suggesting that Ca2+ signals can differ significantly among ribbons within cones. After accounting for potential sources of technical variability in measurements of Ca2+ signals and for contributions from cone-to-cone differences in ICa, we found that the variability in V50 values for ribbon Ca2+ signals within individual cones showed a SD of 2.5 mV. Simulating local differences in Ca2+ channel activity at two ribbons by shifting the V50 value of ICa by ±2.5 mV (1 SD) about the mean suggests that when the membrane depolarizes to −40 mV, two ribbons could experience differences in Ca2+ influx of >45%. Further evidence that local Ca2+ changes at ribbons can be regulated independently was obtained in experiments showing that activation of inhibitory feedback from horizontal cells (HCs) to cones in paired recordings changed both amplitude and V50 of Ca2+ signals at individual ribbons. By varying the strength of synaptic output, differences in voltage dependence and amplitude of Ca2+ signals at individual ribbons shape the information transmitted from cones to downstream neurons in vision. PMID:28744203

The Synaptic and Morphological Basis of Orientation Selectivity in a Polyaxonal Amacrine Cell of the Rabbit Retina.

PubMed

Murphy-Baum, Benjamin L; Taylor, W Rowland

2015-09-30

Much of the computational power of the retina derives from the activity of amacrine cells, a large and diverse group of GABAergic and glycinergic inhibitory interneurons. Here, we identify an ON-type orientation-selective, wide-field, polyaxonal amacrine cell (PAC) in the rabbit retina and demonstrate how its orientation selectivity arises from the structure of the dendritic arbor and the pattern of excitatory and inhibitory inputs. Excitation from ON bipolar cells and inhibition arising from the OFF pathway converge to generate a quasi-linear integration of visual signals in the receptive field center. This serves to suppress responses to high spatial frequencies, thereby improving sensitivity to larger objects and enhancing orientation selectivity. Inhibition also regulates the magnitude and time course of excitatory inputs to this PAC through serial inhibitory connections onto the presynaptic terminals of ON bipolar cells. This presynaptic inhibition is driven by graded potentials within local microcircuits, similar in extent to the size of single bipolar cell receptive fields. Additional presynaptic inhibition is generated by spiking amacrine cells on a larger spatial scale covering several hundred microns. The orientation selectivity of this PAC may be a substrate for the inhibition that mediates orientation selectivity in some types of ganglion cells. Significance statement: The retina comprises numerous excitatory and inhibitory circuits that encode specific features in the visual scene, such as orientation, contrast, or motion. Here, we identify a wide-field inhibitory neuron that responds to visual stimuli of a particular orientation, a feature selectivity that is primarily due to the elongated shape of the dendritic arbor. Integration of convergent excitatory and inhibitory inputs from the ON and OFF visual pathways suppress responses to small objects and fine textures, thus enhancing selectivity for larger objects. Feedback inhibition regulates the strength and speed of excitation on both local and wide-field spatial scales. This study demonstrates how different synaptic inputs are regulated to tune a neuron to respond to specific features in the visual scene. Copyright © 2015 the authors 0270-6474/15/3513336-15$15.00/0.

Spectral and spatial selectivity of luminance vision in reef fish

PubMed Central

Siebeck, Ulrike E.; Wallis, Guy Michael; Litherland, Lenore; Ganeshina, Olga; Vorobyev, Misha

2014-01-01

Luminance vision has high spatial resolution and is used for form vision and texture discrimination. In humans, birds and bees luminance channel is spectrally selective—it depends on the signals of the long-wavelength sensitive photoreceptors (bees) or on the sum of long- and middle-wavelength sensitive cones (humans), but not on the signal of the short-wavelength sensitive (blue) photoreceptors. The reasons of such selectivity are not fully understood. The aim of this study is to reveal the inputs of cone signals to high resolution luminance vision in reef fish. Sixteen freshly caught damselfish, Pomacentrus amboinensis, were trained to discriminate stimuli differing either in their color or in their fine patterns (stripes vs. cheques). Three colors (“bright green”, “dark green” and “blue”) were used to create two sets of color and two sets of pattern stimuli. The “bright green” and “dark green” were similar in their chromatic properties for fish, but differed in their lightness; the “dark green” differed from “blue” in the signal for the blue cone, but yielded similar signals in the long-wavelength and middle-wavelength cones. Fish easily learned to discriminate “bright green” from “dark green” and “dark green” from “blue” stimuli. Fish also could discriminate the fine patterns created from “dark green” and “bright green”. However, fish failed to discriminate fine patterns created from “blue” and “dark green” colors, i.e., the colors that provided contrast for the blue-sensitive photoreceptor, but not for the long-wavelength sensitive one. High resolution luminance vision in damselfish, Pomacentrus amboinensis, does not have input from the blue-sensitive cone, which may indicate that the spectral selectivity of luminance channel is a general feature of visual processing in both aquatic and terrestrial animals. PMID:25324727

Developmental sources of conservation and variation in the evolution of the primate eye.

PubMed

Dyer, Michael A; Martins, Rodrigo; da Silva Filho, Manoel; Muniz, José Augusto P C; Silveira, Luiz Carlos L; Cepko, Constance L; Finlay, Barbara L

2009-06-02

Conserved developmental programs, such as the order of neurogenesis in the mammalian eye, suggest the presence of useful features for evolutionary stability and variability. The owl monkey, Aotus azarae, has developed a fully nocturnal retina in recent evolution. Description and quantification of cell cycle kinetics show that embryonic cytogenesis is extended in Aotus compared with the diurnal New World monkey Cebus apella. Combined with the conserved mammalian pattern of retinal cell specification, this single change in retinal progenitor cell proliferation can produce the multiple alterations of the nocturnal retina, including coordinated reduction in cone and ganglion cell numbers, increase in rod and rod bipolar numbers, and potentially loss of the fovea.

Deflection amplifier for image dissectors

NASA Technical Reports Server (NTRS)

Salomon, P. M.

1977-01-01

Balanced symmetrical y-axis amplifier uses zener-diode level shifting to interface operational amplifiers to high voltage bipolar output stages. Nominal voltage transfer characteristic is 40 differential output volts per input volt; bandwidth, between -3-dB points, is approximately 8 kHz; loop gain is nominally 89 dB with closed loop gain of 26 dB.

Retinal photoreceptors and visual pigments in Boa constrictor imperator.

PubMed

Sillman, A J; Johnson, J L; Loew, E R

2001-09-01

The photoreceptors of Boa constrictor, a boid snake of the subfamily Boinae, were examined with scanning electron microscopy and microspectrophotometry. The retina of B. constrictor is duplex but highly dominated by rods, cones comprising 11% of the photoreceptor population. The rather tightly packed rods have relatively long outer segments with proximal ends that are somewhat tapered. There are two morphologically distinct, single cones. The most common cone by far has a large inner segment and a relatively stout outer segment. The second cone, seen only infrequently, has a substantially smaller inner segment and a finer outer segment. The visual pigments of B. constrictor are virtually identical to those of the pythonine boid, Python regius. Three different visual pigments are present, all based on vitamin A(1.) The visual pigment of the rods has a wavelength of peak absorbance (lambda(max)) at 495 +/- 2 nm. The visual pigment of the more common, large cone has a lambda(max) at 549 +/- 1 nm. The small, rare cone contains a visual pigment with lambda(max) at 357 +/- 2 nm, providing the snake with sensitivity in the ultraviolet. We suggest that B. constrictor might employ UV sensitivity to locate conspecifics and/or to improve hunting efficiency. The data indicate that wavelength discrimination above 430 nm would not be possible without some input from the rods. Copyright 2001 Wiley-Liss, Inc.

Segregation of short-wavelength-sensitive (S) cone signals in the macaque dorsal lateral geniculate nucleus

PubMed Central

Roy, Sujata; Jayakumar, Jaikishan; Martin, Paul R; Dreher, Bogdan; Saalmann, Yuri B; Hu, Daping; Vidyasagar, Trichur R

2009-01-01

An important problem in the study of the mammalian visual system is whether functionally different retinal ganglion cell types are anatomically segregated further up along the central visual pathway. It was previously demonstrated that, in a New World diurnal monkey (marmoset), the neurones carrying signals from the short-wavelength-sensitive (S) cones [blue–yellow (B/Y)-opponent cells] are predominantly located in the koniocellular layers of the dorsal lateral geniculate nucleus (LGN), whereas the red–green (R/G)-opponent cells carrying signals from the medium- and long-wavelength-sensitive cones are segregated in the parvocellular layers. Here, we used extracellular single-unit recordings followed by histological reconstruction to investigate the distribution of color-selective cells in the LGN of the macaque, an Old World diurnal monkey. Cells were classified using cone-isolating stimuli to identify their cone inputs. Our results indicate that the majority of cells carrying signals from S-cones are located either in the koniocellular layers or in the ‘koniocellular bridges’ that fully or partially span the parvocellular layers. By contrast, the R/G-opponent cells are located in the parvocellular layers. We conclude that anatomical segregation of B/Y- and R/G-opponent afferent signals for color vision is common to the LGNs of New World and Old World diurnal monkeys. PMID:19821840

LRRTM4-C538Y novel gene mutation is associated with hereditary macular degeneration with novel dysfunction of ON-type bipolar cells.

PubMed

Kawamura, Yuichi; Suga, Akiko; Fujimaki, Takuro; Yoshitake, Kazutoshi; Tsunoda, Kazushige; Murakami, Akira; Iwata, Takeshi

2018-05-14

The macula is a unique structure in higher primates, where cone and rod photoreceptors show highest density in the fovea and the surrounding area, respectively. The hereditary macular dystrophies represent a heterozygous group of rare disorders characterized by central visual loss and atrophy of the macula and surrounding retina. Here we report an atypical absence of ON-type bipolar cell response in a Japanese patient with autosomal dominant macular dystrophy (adMD). To identify a causal genetic mutation for the adMD, we performed whole-exome sequencing (WES) on four affected and four-non affected members of the family for three generations, and identified a novel p.C538Y mutation in a post-synaptic gene, LRRTM4. WES analysis revealed seven rare genetic variations in patients. We further referred to our in-house WES data from 1360 families with inherited retinal diseases, and found that only p.C538Y mutation in LRRTM4 was associated with adMD-affected patients. Combinatorial filtration using public database of single-nucleotide polymorphism frequency and genotype-phenotype annotated database identified novel mutation in atypical adMD.

Developing an Outcome Measure With High Luminance for Optogenetics Treatment of Severe Retinal Degenerations and for Gene Therapy of Cone Diseases.

PubMed

Cideciyan, Artur V; Roman, Alejandro J; Jacobson, Samuel G; Yan, Boyuan; Pascolini, Michele; Charng, Jason; Pajaro, Simone; Nirenberg, Sheila

2016-06-01

To present stimuli with varied sizes, colors, and patterns over a large range of luminance. The filter bar used in scotopic MP1 was replaced with a custom slide-in tray that introduces light from an external projector driven by an additional computer. MP1 software was modified to provide retinal tracking information to the computer driving the projector. Retinal tracking performance was evaluated by imaging the system input and the output simultaneously with a high-speed video system. Spatial resolution was measured with achromatic and chromatic grating/background combinations over scotopic and photopic ranges. The range of retinal illuminance achievable by the modification was up to 6.8 log photopic Trolands (phot-Td); however, in the current work, only a lower range over -4 to +3 log phot-Td was tested in human subjects. Optical magnification was optimized for low-vision testing with gratings from 4.5 to 0.2 cyc/deg. In normal subjects, spatial resolution driven by rods, short wavelength-sensitive (S-) cones, and long/middle wavelength-sensitive (L/M-) cones was obtained by the choice of adapting conditions and wavelengths of grating and background. Data from a patient with blue cone monochromacy was used to confirm mediation. The modified MP1 can be developed into an outcome measure for treatments in patients with severe retinal degeneration, very low vision, and abnormal eye movements such as those for whom treatment with optogenetics is planned, as well as for patients with cone disorders such as blue cone monochromacy for whom treatment with gene therapy is planned to improve L/M-cone function above a normal complement of rod and S-cone function.

Developing an Outcome Measure With High Luminance for Optogenetics Treatment of Severe Retinal Degenerations and for Gene Therapy of Cone Diseases

PubMed Central

Cideciyan, Artur V.; Roman, Alejandro J.; Jacobson, Samuel G.; Yan, Boyuan; Pascolini, Michele; Charng, Jason; Pajaro, Simone; Nirenberg, Sheila

2016-01-01

Purpose To present stimuli with varied sizes, colors, and patterns over a large range of luminance. Methods The filter bar used in scotopic MP1 was replaced with a custom slide-in tray that introduces light from an external projector driven by an additional computer. MP1 software was modified to provide retinal tracking information to the computer driving the projector. Retinal tracking performance was evaluated by imaging the system input and the output simultaneously with a high-speed video system. Spatial resolution was measured with achromatic and chromatic grating/background combinations over scotopic and photopic ranges. Results The range of retinal illuminance achievable by the modification was up to 6.8 log photopic Trolands (phot-Td); however, in the current work, only a lower range over −4 to +3 log phot-Td was tested in human subjects. Optical magnification was optimized for low-vision testing with gratings from 4.5 to 0.2 cyc/deg. In normal subjects, spatial resolution driven by rods, short wavelength-sensitive (S-) cones, and long/middle wavelength-sensitive (L/M-) cones was obtained by the choice of adapting conditions and wavelengths of grating and background. Data from a patient with blue cone monochromacy was used to confirm mediation. Conclusions The modified MP1 can be developed into an outcome measure for treatments in patients with severe retinal degeneration, very low vision, and abnormal eye movements such as those for whom treatment with optogenetics is planned, as well as for patients with cone disorders such as blue cone monochromacy for whom treatment with gene therapy is planned to improve L/M-cone function above a normal complement of rod and S-cone function. PMID:27309625

Chromatic summation and receptive field properties of blue-on and blue-off cells in marmoset lateral geniculate nucleus.

PubMed

Eiber, C D; Pietersen, A N J; Zeater, N; Solomon, S G; Martin, P R

2017-11-22

The "blue-on" and "blue-off" receptive fields in retina and dorsal lateral geniculate nucleus (LGN) of diurnal primates combine signals from short-wavelength sensitive (S) cone photoreceptors with signals from medium/long wavelength sensitive (ML) photoreceptors. Three questions about this combination remain unresolved. Firstly, is the combination of S and ML signals in these cells linear or non-linear? Secondly, how does the timing of S and ML inputs to these cells influence their responses? Thirdly, is there spatial antagonism within S and ML subunits of the receptive field of these cells? We measured contrast sensitivity and spatial frequency tuning for four types of drifting sine gratings: S cone isolating, ML cone isolating, achromatic (S + ML), and counterphase chromatic (S - ML), in extracellular recordings from LGN of marmoset monkeys. We found that responses to stimuli which modulate both S and ML cones are well predicted by a linear sum of S and ML signals, followed by a saturating contrast-response relation. Differences in sensitivity and timing (i.e. vector combination) between S and ML inputs are needed to explain the amplitude and phase of responses to achromatic (S + ML) and counterphase chromatic (S - ML) stimuli. Best-fit spatial receptive fields for S and/or ML subunits in most cells (>80%) required antagonistic surrounds, usually in the S subunit. The surrounds were however generally weak and had little influence on spatial tuning. The sensitivity and size of S and ML subunits were correlated on a cell-by-cell basis, adding to evidence that blue-on and blue-off receptive fields are specialised to signal chromatic but not spatial contrast. Copyright © 2017 Elsevier Ltd. All rights reserved.

Boundary-layer instability & transition on a flared cone in a Mach 6 quiet wind tunnel

NASA Astrophysics Data System (ADS)

Hofferth, Jerrod; Saric, William

2011-11-01

Measurements of boundary-layer transition location and instability growth on a sharp-tipped 5°-half-angle flared cone were conducted in a low-disturbance Mach 6 wind tunnel at a freestream unit Reynolds number of 10 × 106/m. Under quiet flow at these conditions, the boundary layer becomes transitional near the base of the cone, where significant second-mode instability growth is evident. Transition location is determined using an array of embedded thermocouples, and instability development is observed in mean and fluctuating mass flux data using hotwire anemometry. The present work seeks to reproduce and build upon previous experiments which used the same test article and similar diagnostics in the facility's former installation at NASA Langley. Together with comprehensive measurements of the freestream disturbance environment, these baseline cone data characterize the facility's performance relative to that in its previous installation. In addition, the current campaign establishes experimental readiness for future research, which will study the effects of periodic surface roughness and controlled-input disturbances. AFOSR/NASA National Center for Hypersonic Research in Laminar-Turbulent Transition; Grant FA9550-09-1-0341.

Impairment of photoreceptor ribbon synapses in a novel Pomt1 conditional knockout mouse model of dystroglycanopathy.

PubMed

Rubio-Fernández, Marcos; Uribe, Mary Luz; Vicente-Tejedor, Javier; Germain, Francisco; Susín-Lara, Cristina; Quereda, Cristina; Montoliu, Lluis; de la Villa, Pedro; Martín-Nieto, José; Cruces, Jesús

2018-06-04

Hypoglycosylation of α-dystroglycan (α-DG) resulting from deficiency of protein O-mannosyltransferase 1 (POMT1) may cause severe neuromuscular dystrophies with brain and eye anomalies, named dystroglycanopathies. The retinal involvement of these disorders motivated us to generate a conditional knockout (cKO) mouse experiencing a Pomt1 intragenic deletion (exons 3-4) during the development of photoreceptors, mediated by the Cre recombinase expressed from the cone-rod homeobox (Crx) gene promoter. In this mouse, retinal α-DG was unglycosylated and incapable of binding laminin. Retinal POMT1 deficiency caused significant impairments in both electroretinographic recordings and optokinetic reflex in Pomt1 cKO mice, and immunohistochemical analyses revealed the absence of β-DG and of the α-DG-interacting protein, pikachurin, in the outer plexiform layer (OPL). At the ultrastructural level, noticeable alterations were observed in the ribbon synapses established between photoreceptors and bipolar cells. Therefore, O-mannosylation of α-DG in the retina carried out by POMT1 is crucial for the establishment of proper synapses at the OPL and transmission of visual information from cones and rods to their postsynaptic neurons.

Edges, colour and awareness in blindsight.

PubMed

Alexander, Iona; Cowey, Alan

2010-06-01

It remains unclear what is being processed in blindsight in response to faces, colours, shapes, and patterns. This was investigated in two hemianopes with chromatic and achromatic stimuli with sharp or shallow luminance or chromatic contrast boundaries or temporal onsets. Performance was excellent only when stimuli had sharp spatial boundaries. When discrimination between isoluminant coloured Gaussians was good it declined to chance levels if stimulus onset was slow. The ability to discriminate between instantaneously presented colours in the hemianopic field depended on their luminance, indicating that wavelength discrimination totally independent of other stimulus qualities is absent. When presented with narrow-band colours the hemianopes detected a stimulus maximally effective for S-cones but invisible to M- and L-cones, indicating that blindsight is mediated not just by the mid-brain, which receives no S-cone input, or that the rods contribute to blindsight. The results show that only simple stimulus features are processed in blindsight. 2010 Elsevier Inc. All rights reserved.

A sign-reversing pathway from rods to double and single cones in the retina of the tiger salamander.

PubMed

Attwell, D; Werblin, F S; Wilson, M; Wu, S M

1983-03-01

Signal transmission between rods and cones was studied by passing current into a rod and recording the voltage response in a nearby double or single cone and vice versa. Two types of rod-cone interaction were found. Between immediately adjacent rods and cones, passage of current into either receptor elicited in the other receptor a sustained voltage response of the same sign as the injected current. These signals were still seen in the presence of Co2+, and are probably mediated by the electrical synapses which have been seen anatomically between adjacent rods and cones. In addition to this short-range sign-preserving interaction, passing current into a rod elicited a transient sign-inverted signal in cones up to at least 80 micron from the injected rod. No such response was seen in rods for current injection into cones. This signal was greatly reduced by Co2+ ions. Hyperpolarization of the cone to about -65 mV, with about 0.1 nA current, reversed this signal, which is presumed to be mediated by a chemical synaptic input to cones. Light flashes suppressed the sign-inverted signal for a period which was longer for brighter flashes. The time of reappearance of the signal was correlated with the return of the rod and horizontal cell potentials to their dark levels. This suppression could also be produced by an annulus of light which produced no light response in the receptors at the centre of the annulus, but which did polarize horizontal cells under the centre of the annulus. The wave form of the sign-inverted signal was similar to that produced in horizontal cells by current injection into rods, but of opposite sign. If an electrode was left in a cone for some time, the normal hyperpolarizing light response diminished, leaving a depolarizing response produced, presumably, by feed-back from horizontal cells. This signal was reversed when the cone was hyperpolarized with about 0.1 nA current. These data suggest that the sign-inverted response is mediated by feed-back from horizontal cells and, assuming that depolarization increases the rate of release of horizontal cell synaptic transmitter, then the feed-back transmitter opens channels in the cone membrane whose currents have a reversal potential around -65 mV.

Tracking blue cone signals in the primate brain.

PubMed

Jayakumar, Jaikishan; Dreher, Bogdan; Vidyasagar, Trichur R

2013-05-01

In this paper, we review the path taken by signals originating from the short wavelength sensitive cones (S-cones) in Old World and New World primates. Two types of retinal ganglion cells (RGCs) carrying S-cone signals (blue-On and blue-Off cells) project to the dorsal lateral geniculate nucleus (dLGN) in the thalamus. In all primates, these S-cone signals are relayed through the 'dust-like' (konis in classical Greek) dLGN cells. In New World primates such as common marmoset, these very small cells are known to form distinct and spatially extensive, koniocellular layers. Although in Old World primates, such as macaques, koniocellular layers tend to be very thin, the adjacent parvocellular layers contain distinct koniocellular extensions. It appears that all S-cone signals are relayed through such konio cells, whether they are in the main koniocellular layers or in their colonies within the parvocellular layers of the dLGN. In the primary visual cortex, these signals begin to merge with the signals carried by the other two principal parallel channels, namely the magnocellular and parvocellular channels. This article will also review the possible routes taken by the S-cone signals to reach one of the topographically organised extrastriate visual cortical areas, the middle temporal area (area MT). This area is the major conduit for signals reaching the parietal cortex. Alternative visual inputs to area MT not relayed via the primary visual cortex area (V1) may provide the neurological basis for the phenomenon of 'blindsight' observed in human and non-human primates, who have partial or complete damage to the primary visual cortex. Short wavelength sensitive cone (S-cone) signals to area MT may also play a role in directing visual attention with possible implications for understanding the pathology in dyslexia and some of its treatment options. © 2012 The Authors. Clinical and Experimental Optometry © 2012 Optometrists Association Australia.

Analysis of pressure losses in the diffuser of a control valve

NASA Astrophysics Data System (ADS)

Turecký, Petr; Mrózek, Lukáš; Tajč, Ladislav; Kolovratník, Michal

The pressure loss in the diffuser of a control valve is evaluated by using CFD computations. Pressure ratios and lifts of a cone for the recommended flow characteristics of an experimental turbine are considered. The pressure loss in a valve is compared with the pressure loss in a nozzle, i.e. the embodiment of the valve without a cone. Computations are carried out for the same mass flow. Velocity profiles are evaluated in both versions of computations. Comparison of computed pressure losses, with the loss evaluated by using relations for diffusers with the ideal velocity conditions in the input cross-section, is carried out.

Martian Rootless Cones as Indicators of Recent Deposits of Shallow Equatorial Ground Ice

NASA Astrophysics Data System (ADS)

Lanagan, P. D.; McEwen, A. S.; Keszthelyi, L. P.; Thordarson, T.

2001-05-01

Small, cratered cones have been identified in high-resolution Mars Orbiter Camera images of the Cerberus Plains and Amazonis Planitia, Mars [1].These cones occur in small clusters independent of obvious fissures, are superimposed on fresh lava flows, and do not appear to issue lavas themselves. Observed cones have basal diameters <250m and large summit craters. The structures are similar in both morphology and dimensions to the larger of Icelandic rootless cones,or pseudocraters [2], which form due to phreatomagmatic explosions caused by mechanical mixtures of tube-fed lavas with near-surface water-saturated substrates[3]. If the martian cones form in a similar manner as terrestrial rootless cones,then they may provide constraints on the spatial and temporal distribution of martian ground ice. Lavas associated with the western Amazonis cone fields(24N, 171W) show well-preserved surface morphologies and few superimposed impact craters. Impact crater statistics indicate that these lavas and superimposed cones may have been emplaced less than 10 Ma, indicating near-surface ice must have been present at the time. The presence of young rootless cones helps constrain the origins of ground ice. Relic ground ice is unlikely to be a volatile source for rootless eruptions as regolith in equatorial regions is likely to be desiccated to a depth of 200-m [4]. Vapor exchange between the regolith and atmosphere due to obliquity variations [5] may input enough water into the subsurface to reproduce martian cones of observed diameters calculated by explosion models[6]. However, surficial waters released in outflow events may be required to recharge requisite quantities of ground ice. Most proposed rootless cone fields appear in or close to fluvial features of the Cerberus Plains and Marte Valles[7]. Nested summit craters of some cones indicate a multi-stage constructional process, which would require recharge of aquifers beneath the erupting cones. Such a process would require the substrate to be permeable and contain enough ground ice to allow water to flow to the explosion point. [1]Lanagan, P. D. et al.(2001)Geophys Res Let, submitted. [2]Thorarinsson, S.(1953)Bull Vol, 14, 3-44. [3]Thordarson, T.(2000)Volcano-Ice Interactions on Earth and Mars, 36. [4]Clifford, S. M., and Hillel, D.(1983)J Geophys Res, 88, 2456-2474. [5]Mellon, M. T., and B. M. Jakosky.(1995)J Geophys Res, 100, 11781-11799. [6]Fagents, S. A. and R. Greeley.(2000)Volcano-Ice Interactions on Earth and Mars, 13. [7]Burr, D. M. et al.(2001)Geophys Res Abs.

Vigabatrin can enhance electroretinographic responses in pigmented and albino rats.

PubMed

Akula, James D; Noonan, Emily R; Di Nardo, Alessia; Favazza, Tara L; Zhang, Nan; Sahin, Mustafa; Hansen, Ronald M; Fulton, Anne B

2015-08-01

To evaluate the effects of the antiepileptic medication vigabatrin (VGB) on the retina of pigmented rats. Scotopic and photopic electroretinograms were recorded from dark- and light-adapted Long-Evans (pigmented) and Sprague Dawley (albino) rats administered, daily, 52-55 injections of 250 mg·kg(-1)·day(-1) VGB or 25-26 injections of 500 mg·kg(-1)·day(-1) VGB, or a corresponding number of sham injections. Sensitivity and saturated amplitude of the rod photoresponse (S, Rm(P3)) and postreceptor response (1/σ, Vm) were derived, as were sensitivity and amplitude of the cone-mediated postreceptor response (1/σ(cone), Vm(cone)). The oscillatory potentials and responses to a series of flickering lights (6.25, 12.5, 25 and 50 Hz) were studied in the time and frequency domains. A subset of rats' eyes was harvested for Western blotting or histology. Of the parameters derived from dark-adapted ERG responses, in both pigmented and albino rats, VGB repeatedly and reliably enhanced electroretinographic parameters; no significant ERG deficits were noted. No significant alterations were observed in ER/oxidative stress or in the Akt cell death/survival pathway. There were migrations of photoreceptor nuclei toward the RPE and outgrowths of bipolar cell dendrites into the outer nuclear layer in VGB-treated rats; these were never observed in sham-treated animals. Although VGB is associated with retinal dysfunction in patients and VGB toxicity has been demonstrated by other laboratories in the albino rat, in our pigmented and albino rats, VGB did not induce deficits in, but rather enhanced, retinal function. Nonetheless, retinal neuronal dysplasia was observed.

Characterization of depressive States in bipolar patients using wearable textile technology and instantaneous heart rate variability assessment.

PubMed

Valenza, Gaetano; Citi, Luca; Gentili, Claudio; Lanata, Antonio; Scilingo, Enzo Pasquale; Barbieri, Riccardo

2015-01-01

The analysis of cognitive and autonomic responses to emotionally relevant stimuli could provide a viable solution for the automatic recognition of different mood states, both in normal and pathological conditions. In this study, we present a methodological application describing a novel system based on wearable textile technology and instantaneous nonlinear heart rate variability assessment, able to characterize the autonomic status of bipolar patients by considering only electrocardiogram recordings. As a proof of this concept, our study presents results obtained from eight bipolar patients during their normal daily activities and being elicited according to a specific emotional protocol through the presentation of emotionally relevant pictures. Linear and nonlinear features were computed using a novel point-process-based nonlinear autoregressive integrative model and compared with traditional algorithmic methods. The estimated indices were used as the input of a multilayer perceptron to discriminate the depressive from the euthymic status. Results show that our system achieves much higher accuracy than the traditional techniques. Moreover, the inclusion of instantaneous higher order spectra features significantly improves the accuracy in successfully recognizing depression from euthymia.

Rod-driven OFF pathway responses in the distal retina: dark-adapted flicker electroretinogram in mouse.

PubMed

Lei, Bo

2012-01-01

The rodent retina does not exhibit a positive OFF-response in the electroretinogram (ERG), which makes it difficult to evaluate its OFF-pathway functions in vivo. We studied the rod-driven OFF pathway responses by using a dark-adapted 10-Hz flicker ERG procedure in mouse. Conventional ERGs and 10-Hz dark-adapted flicker ERGs were obtained in wild-type mice (C57BL/6), in mice with pure rod (cpfl1) or pure cone (rho(-/-)) function, and in nob1 mice which have a selective ON-pathway defect. To isolate the response from ON or OFF pathway, glutamate analogs 2-amino-4-phosphobutyric acid (APB, an ON pathway blocker) and cis-2, 3-piperidine-dicarboxylic acid (PDA, an OFF pathway blocker), were injected intravitreally. The amplitude-intensity profile of the dark-adapted 10-Hz flicker ERG in the wild-type mice exhibits two peaks at middle and high light intensities. The two peaks represent rod- and cone-driven responses respectively. In APB-treated C57BL/6 mice and in nob1 mice, the dark-adapted ERG b-waves were absent. However, both rod- and cone-driven OFF pathway responses were evident with flicker ERG recording. At middle light intensities that activate only rod system, the flicker ERG responses in saline-injected nob1 mice were similar to those in APB-injected cpfl1 mice and wild-type mice. These responses are sensitive to PDA. The amplitudes of these rod-driven OFF pathway responses were approximately 20% of the total rod-driven flicker ERG responses. We demonstrate that the rod-OFF bipolar cell pathway is functional in the outer retina. The dark-adapted flicker ERG is practical for the evaluation of rod- and cone-driven responses, and the residual OFF pathway signals in subjects with ON pathway defects.

Robust syntaxin-4 immunoreactivity in mammalian horizontal cell processes

PubMed Central

HIRANO, ARLENE A.; BRANDSTÄTTER, JOHANN HELMUT; VILA, ALEJANDRO; BRECHA, NICHOLAS C.

2009-01-01

Horizontal cells mediate inhibitory feed-forward and feedback communication in the outer retina; however, mechanisms that underlie transmitter release from mammalian horizontal cells are poorly understood. Toward determining whether the molecular machinery for exocytosis is present in horizontal cells, we investigated the localization of syntaxin-4, a SNARE protein involved in targeting vesicles to the plasma membrane, in mouse, rat, and rabbit retinae using immunocytochemistry. We report robust expression of syntaxin-4 in the outer plexiform layer of all three species. Syntaxin-4 occurred in processes and tips of horizontal cells, with regularly spaced, thicker sandwich-like structures along the processes. Double labeling with syntaxin-4 and calbindin antibodies, a horizontal cell marker, demonstrated syntaxin-4 localization to horizontal cell processes; whereas, double labeling with PKC antibodies, a rod bipolar cell (RBC) marker, showed a lack of co-localization, with syntaxin-4 immunolabeling occurring just distal to RBC dendritic tips. Syntaxin-4 immunolabeling occurred within VGLUT-1-immunoreactive photoreceptor terminals and underneath synaptic ribbons, labeled by CtBP2/RIBEYE antibodies, consistent with localization in invaginating horizontal cell tips at photoreceptor triad synapses. Vertical sections of retina immunostained for syntaxin-4 and peanut agglutinin (PNA) established that the prominent patches of syntaxin-4 immunoreactivity were adjacent to the base of cone pedicles. Horizontal sections through the OPL indicate a one-to-one co-localization of syntaxin-4 densities at likely all cone pedicles, with syntaxin-4 immunoreactivity interdigitating with PNA labeling. Pre-embedding immuno-electron microscopy confirmed the subcellular localization of syntaxin-4 labeling to lateral elements at both rod and cone triad synapses. Finally, co-localization with SNAP-25, a possible binding partner of syntaxin-4, indicated co-expression of these SNARE proteins in the same subcellular compartment of the horizontal cell. Taken together, the strong expression of these two SNARE proteins in the processes and endings of horizontal cells at rod and cone terminals suggests that horizontal cell axons and dendrites are likely sites of exocytotic activity. PMID:17640443

Development of chip passivated monolithic complementary MISFET circuits with beam leads

NASA Technical Reports Server (NTRS)

Ragonese, L. J.; Kim, M. J.; Corrie, B. L.; Brouillette, J. W.; Warr, R. E.

1972-01-01

The results are presented of a program to demonstrate the processes for fabricating complementary MISFET beam-leaded circuits, which, potentially, are comparable in quality to available bipolar beam-lead chips that use silicon nitride passivation in conjunction with a platinum-titanium-gold metal system. Materials and techniques, different from the bipolar case, were used in order to be more compatible with the special requirements of fully passivated complementary MISFET devices. Two types of circuits were designed and fabricated, a D-flip-flop and a three-input NOR/NAND gate. Fifty beam-leaded chips of each type were constructed. A quality and reliability assurance program was performed to identify failure mechanisms. Sample tests and inspections (including destructive) were developed to measure the physical characteristics of the circuits.

Immunocytochemical localization of the NMDA-R2A receptor subunit in the cat retina.

PubMed

Goebel, D J; Aurelia, J L; Tai, Q; Jojich, L; Poosch, M S

1998-10-19

Immunocytochemical studies were performed to determine the distribution and cellular localization of the NMDA-R2A receptor subunit (R2A) in the cat retina. R2A-immunoreactivity (R2A-IR) was noted in all layers of the retina, with specific localizations in the outer segments of red/green and blue cone photoreceptors, B-type horizontal cells, several types of amacrine cells, Müller cells and the majority of cells in the ganglion cell layer. In the inner nuclear layer, 48% of all cells residing in the amacrine cell layer were R2A-IR including a cell resembling the GABAergic A17 amacrine cell. Interestingly, the AII rod amacrine cell was devoid of R2A-IR. Although the localization of the R2A subunit was anticipated in ganglion cells, amacrines and Müller cells, the presence of this receptor subunit to the cells in the outer retina was not expected. Here, both the R2A and the R2B subunits were found to be present in the outer segments of cone photoreceptors and to the tips of rod outer segments. Although the function of these receptor subunits in rod and cone photoreceptors remains to be determined, the fact that both R2A and R2B receptor subunits are localized to cone outer segments suggests a possible alternative pathway for calcium entry into a region where this cation plays such a crucial role in the process of phototransduction. To further classify the cells that display NR2A-IR, we performed dual labeling experiments showing the relationship between R2A-labeled cells with GABA. Results showed that all GABAergic-amacrines and displaced amacrines express the R2A-subunit protein. In addition, approximately 11% of the NR2A-labeled amacrines, did not stain for GABA. These findings support pharmacological data showing that NMDA directly facilitates GABA release in retina and retinal cultures [I.L. Ferreira, C.B. Duarte, P.F. Santos, C.M. Carvalho, A.P. Carvalho, Release of [3H]GABA evoked by glutamate receptor agonist in cultured chick retinal cells: effect of Ca2+, Brain Res. 664 (1994) 252-256; G.D. Zeevalk, W.J. Nicklas, Action of the anti-ischemic agent ifenprodil on N-methyl-d-aspartate and kainate-mediated excitotoxicity, Brain Res. 522 (1990) 135-139; R. Huba, H.D. Hofmann, Transmitter-gated currents of GABAergic amacrine-like cells in chick retinal cultures, Vis. Neurosci. 6 (1991) 303-314; M. Yamashita, R. Huba, H.D. Hofmann, Early in vitro development of voltage- and transmitter-gated currents in GABAergic amacrine cells, Dev. Brain Res. 82 (1994) 95-102; R. Ientile, S. Pedale, V. Picciurro, V. Macaione, C. Fabiano, S. Macaione, Nitric oxide mediates NMDA-evoked [3H]GABA release from chick retina cells, FEBS Lett. 417 (1997) 345-348; R.C. Kubrusly, M.C. deMello, F.G. deMello, Aspartate as a selective NMDA agonist in cultured cells from the avian retina, Neurochem. Intl. 32 (1998) 47-52] or reduction of GABA in vivo [N.N. Osborn, A.J. Herrera, The effect of experimental ischaemia and excitatory amino acid agonist on the GABA and serotonin immunoreactivities in the rabbit retina, Neurosci. 59 (1994) 1071-1081]. Since the majority of GABAergic synapses in the inner retina are onto both rod and cone bipolar axon terminals [R.G. Pourcho, M.T. Owzcarzak, Distribution of GABA immunoreactivity in the cat retina: A light and electron-microscopic study, Vis. Neurosci. 2 (1989) 425-435], we hypothesize that the NMDA-receptor plays a crucial role in providing feedback inhibition onto rod and cone bipolar cells. Copyright 1998 Elsevier Science B.V.

Models for determining the geometrical properties of halo coronal mass ejections

NASA Astrophysics Data System (ADS)

Zhao, X.; Liu, Y.

2005-12-01

To this day, the prediction of space weather effects near the Earth suffer from a fundamental problem: the necessary condition for determining whether or not and when a part of the huge interplanetary counterpart (ICME) of frontside halo coronal mass ejections (CMEs) is able to hit the Earth and generate goemagnetic storms, i.e., the real angular width, the propagation direction and speed of the CMEs, cannot be measured directly because of the unfavorable geometry. To inverse these geometrical and kinematical properties we have recently developed a few geometrical models, such as the cone model, the ice cream cone model, and the spherical cone model. The inversing solution of the cone model for the 12 may 1997 halo CME has been used as an input to the ENLIL model (a 3D MHD solar wind code) and successfully predicted the ICME near the Earth (Zhao, Plukett & Liu, 2002; Odstrcil, Riley & Zhao, 2004). After briefly describing the geometrical models this presentation will discuss: 1. What kind of halo CMEs can be inversed? 2. How to select the geometrical models given a specific halo CME? 3. Whether or not the inversing solution is unique?

Stability and sensitivity analysis of hypersonic flow past a blunt cone

NASA Astrophysics Data System (ADS)

Nichols, Joseph W.; Cook, David; Brock, Joseph M.; Candler, Graham V.

2017-11-01

We investigate the effects of nosetip bluntness and low-level distributed roughness on instabilities leading to transition on a 7 degree half-angle blunt cone at Mach 10. To study the sensitivity of boundary layer instabilities to bluntness and roughness, we numerically extract Jacobian matrices directly from the unstructured hypersonic flow solver US3D. These matrices govern the dynamics of small perturbations about otherwise laminar base flows. We consider the frequency response of the resulting linearized dynamical system between different input and output locations along the cone, including close to the nosetip. Using adjoints, our method faithfully captures effects of complex geometry such as strong curvature and roughness that lead to flow acceleration and localized heating in this region. These effects violate the assumption of a slowly-varying base flow that underpins traditional linear stability analyses. We compare our results, which do not rely upon this assumption, to experimental measurements of a Mach 10 blunt cone taken at the AEDC Hypervelocity Ballistic Range G facility. In particular, we assess whether effects of complex geometry can explain discrepancies previously noted between traditional stability analysis and observations. This work is supported by the Office of Naval Research through Grant Number N00014-17-1-2496.

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

NASA Astrophysics Data System (ADS)

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 CBIC-U2, 4 GHz f(sub 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 micron pitch double-sided silicon strip detector. The chip measures 6.8 mm by 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 four times the noise level, a 16 nsec time-walk for 1.25 to 10 fC signals is achieved using a time-walk compensation network. Irradiation tests at TRIUMF to a Phi = 10(exp 14) protons/sq cm have been performed on the IC, demonstrating the radiation hardness of the complementary bipolar process.

Local traction force in the proximal leading process triggers nuclear translocation during neuronal migration.

PubMed

Umeshima, Hiroki; Nomura, Ken-Ichi; Yoshikawa, Shuhei; Hörning, Marcel; Tanaka, Motomu; Sakuma, Shinya; Arai, Fumihito; Kaneko, Makoto; Kengaku, Mineko

2018-04-05

Somal translocation in long bipolar neurons is regulated by actomyosin contractile forces, yet the precise spatiotemporal sites of force generation are unknown. Here we investigate the force dynamics generated during somal translocation using traction force microscopy. Neurons with a short leading process generated a traction force in the growth cone and counteracting forces in the leading and trailing processes. In contrast, neurons with a long leading process generated a force dipole with opposing traction forces in the proximal leading process during nuclear translocation. Transient accumulation of actin filaments was observed at the dipole center of the two opposing forces, which was abolished by inhibition of myosin II activity. A swelling in the leading process emerged and generated a traction force that pulled the nucleus when nuclear translocation was physically hampered. The traction force in the leading process swelling was uncoupled from somal translocation in neurons expressing a dominant negative mutant of the KASH protein, which disrupts the interaction between cytoskeletal components and the nuclear envelope. Our results suggest that the leading process is the site of generation of actomyosin-dependent traction force in long bipolar neurons, and that the traction force is transmitted to the nucleus via KASH proteins. Copyright © 2018 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.

[Melanoma-associated retinopathy with night blindness. Case report].

PubMed

Klopfer, M; Schmidt, T; Leipert, K P; Ugi, I; Boeck, K; Hofmann, S

1997-08-01

Night blindness is usually symptomatic of retinal dysfunction. However, apart from congenital forms of night blindness such as congenital stationary night blindness (CSNB) and pigmentary retinopathy without clumping of pigment, the acquired forms of night blindness present a particular diagnostic challenge to the ophthalmologist. A 51-year-old patient with formerly healthy eyes presented with malignant skin melanoma and sudden night blindness. Along with reduced acuity, concentric visual field limitation, and a marked decrease in sensitivity of the retinal rods and cones in adaptometrical tests, significantly reduced b waves and intact a waves were registered in the flash-ERG of both eyes with otherwise inconspicuous morphologic findings. Furthermore, serum levels of antibodies (IgG) against retinal bipolar cells were found to be increased. Results indicate the presence of melanoma-associated retinopathy (MAR), which-like carcinoma-associated retinopathy (CAR)-ranks among the tumor-associated diseases of the retina. CAR, MAR, and CSNB can be differentiated immunohistochemically by serum autoantibody determination and electrophysiologically by flash-ERG. As opposed to CAR, the immune response in the case of MAR is not to antigens of photoreceptors and ganglion cells, but to retinal so-called ON-depolarizing bipolar cells mainly connected in series to the rods. In addition, a waves are intact and b waves extinct, resembling the situation of CSNB.

LOW CONDUCTANCE HCN1 ION CHANNELS AUGMENT THE FREQUENCY RESPONSE OF ROD AND CONE PHOTORECEPTORS

PubMed Central

Barrow, Andrew J.; Wu, Samuel M.

2009-01-01

Hyperpolarization-activated cyclic nucleotide gated (HCN) ion channels are expressed in several tissues throughout the body, including the heart, the CNS, and the retina. HCN channels are found in many neurons in the retina, but their most established role is in generating the hyperpolarization-activated current, Ih, in photoreceptors. This current makes the light response of rod and cone photoreceptors more transient, an effect similar to that of a high-pass filter. A unique property of HCN channels is their small single channel current, which is below the thermal noise threshold of measuring electronics. We use nonstationary fluctuation analysis (NSFA) in the intact retina to estimate the conductance of single HCN channels, revealing a conductance of approximately 650 fS in both rod and cone photoreceptors. We also analyze the properties of HCN channels in salamander rods and cones, from the biophysical to the functional level, showing that HCN1 is the predominant isoform in both cells, and demonstrate how HCN1 channels speed up the light response of both rods and cones under distinct adaptational conditions. We show that in rods and cones, HCN channels increase the natural frequency response of single cells by modifying the photocurrent input, which is limited in its frequency response by the speed of a molecular signaling cascade. In doing so, HCN channels form the first of several systems in the retina that augment the speed of the visual response, allowing an animal to perceive visual stimuli that change more quickly than the underlying photocurrent. PMID:19420251

Photons, clocks, and consciousness

NASA Technical Reports Server (NTRS)

Brainard, George C.; Hanifin, John P.

2005-01-01

Light profoundly impacts human consciousness through the stimulation of the visual system and powerfully regulates the human circadian system, which, in turn, has a broad regulatory impact on virtually all tissues in the body. For more than 25 years, the techniques of action spectroscopy have yielded insights into the wavelength sensitivity of circadian input in humans and other mammalian species. The seminal discovery of melanopsin, the photopigment in intrinsically photosensitive retinal ganglion cells, has provided a significant turning point for understanding human circadian phototransduction. Action spectra in humans show that the peak wavelength sensitivity for this newly discovered sensory system is within the blue portion of the spectrum. This is fundamentally different from the three-cone photopic visual system, as well as the individual rod and cone photoreceptor peaks. Studies on rodents, nonhuman primates, and humans indicate that despite having a different wavelength fingerprint, these classic visual photoreceptors still provide an element of input to the circadian system. These findings open the door to innovations in light therapy for circadian and affective disorders, as well as possible architectural light applications.

Prediction of lithium response in first-episode mania using the LITHium Intelligent Agent (LITHIA): Pilot data and proof-of-concept.

PubMed

Fleck, David E; Ernest, Nicholas; Adler, Caleb M; Cohen, Kelly; Eliassen, James C; Norris, Matthew; Komoroski, Richard A; Chu, Wen-Jang; Welge, Jeffrey A; Blom, Thomas J; DelBello, Melissa P; Strakowski, Stephen M

2017-06-01

Individualized treatment for bipolar disorder based on neuroimaging treatment targets remains elusive. To address this shortcoming, we developed a linguistic machine learning system based on a cascading genetic fuzzy tree (GFT) design called the LITHium Intelligent Agent (LITHIA). Using multiple objectively defined functional magnetic resonance imaging (fMRI) and proton magnetic resonance spectroscopy ( 1 H-MRS) inputs, we tested whether LITHIA could accurately predict the lithium response in participants with first-episode bipolar mania. We identified 20 subjects with first-episode bipolar mania who received an adequate trial of lithium over 8 weeks and both fMRI and 1 H-MRS scans at baseline pre-treatment. We trained LITHIA using 18 1 H-MRS and 90 fMRI inputs over four training runs to classify treatment response and predict symptom reductions. Each training run contained a randomly selected 80% of the total sample and was followed by a 20% validation run. Over a different randomly selected distribution of the sample, we then compared LITHIA to eight common classification methods. LITHIA demonstrated nearly perfect classification accuracy and was able to predict post-treatment symptom reductions at 8 weeks with at least 88% accuracy in training and 80% accuracy in validation. Moreover, LITHIA exceeded the predictive capacity of the eight comparator methods and showed little tendency towards overfitting. The results provided proof-of-concept that a novel GFT is capable of providing control to a multidimensional bioinformatics problem-namely, prediction of the lithium response-in a pilot data set. Future work on this, and similar machine learning systems, could help assign psychiatric treatments more efficiently, thereby optimizing outcomes and limiting unnecessary treatment. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

PubMed

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 the SNR of the spike output. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Asymmetric effects of luminance and chrominance in the watercolor illusion

PubMed Central

Coia, Andrew J.; Crognale, Michael A.

2014-01-01

When bounded by a line of sufficient contrast, the desaturated hue of a colored line will spread over an enclosed area, an effect known as the watercolor illusion. The contrast of the two lines can be in luminance, chromaticity, or a combination of both. The effect is most salient when the enclosing line has greater contrast with the background than the line that induces the spreading color. In most prior experiments with watercolor spreading, the luminance of both lines has been lower than the background. An achromatic version of the illusion exists where a dark line will spread while being bounded by either a darker or brighter line. In a previous study we measured the strength of the watercolor effect in which the colored inducing line was isoluminant to the background, and found an illusion for both brighter and darker achromatic outer contours. We also found the strength of spreading is stronger for bluish (+S cone input) colors compared to yellowish (−S cone input) ones, when bounded by a dark line. The current study set out to measure the hue dependence of the watercolor illusion when inducing colors are flanked with brighter (increment) as opposed to darker outer lines. The asymmetry in the watercolor effect with S cone input was enhanced when the inducing contrast was an increment rather than a decrement. Further experiments explored the relationship between the perceived contrast of these chromatic lines when paired with luminance increments and decrements and revealed that the perceived contrast of luminance increments and decrements is dependent on which isoluminant color they are paired with. In addition to known hue asymmetries in the watercolor illusion there are asymmetries between luminance increments and decrements that are also hue dependent. These latter asymmetries may be related to the perceived contrast of the hue/luminance parings. PMID:25309396

The properties of single cones isolated from the tiger salamander retina

PubMed Central

Attwell, David; Werblin, Frank S.; Wilson, Martin

1982-01-01

1. The properties of isolated single cones were studied using the voltage-clamp technique, with two micro-electrodes inserted under visual control. 2. Single cones had input resistances, when impaled with two electrodes, of up to 270 MΩ. This is probably lower than the true membrane resistance, because of damage by the impaling electrodes. The cone capacitance was about 85 pF. 3. The cone membrane contains a time-dependent current, IB, controlled by voltage, and a separate photosensitive current. 4. The gated current, IB, is an inward current with a reversal potential around -25 mV. It is activated by hyperpolarization over the range -30 to -80 mV, and at constant voltage obeys first order (exponential) kinetics. The gating time constant is typically 50 ms at the resting potential of -45 mV, rises to 170 ms at -70 mV, and decreases for further hyperpolarization. 5. The spectral sensitivity curve of the cone light response peaks at 620 nm wave-length, and is narrower than the nomogram for vitamin A2-based pigments. The light responses of isolated cones are spectrally univariant. 6. Voltage-clamped photocurrents were recorded at various membrane potentials, for light steps of various intensities. The photocurrent reversed at around -8 mV. The time course of the photocurrent, for a given intensity, was approximately independent of voltage (although its magnitude was voltage-dependent). The shape of the peak current—voltage relation of the light-sensitive current was independent of light intensity (although its magnitude was intensity-dependent). 7. These results can be explained if: (a) light simply changes the number of photosensitive channels open, without altering the properties of an open channel; (b) the reactions controlling the production of internal transmitter, the binding of internal transmitter to the photosensitive channels, and the closing and opening of the channels are unaffected by the electric field in the cone membrane, even though at least some of these reactions take place in the membrane. 8. IB plays only a small role in shaping the cone voltage response to light. ImagesPlate 1 PMID:7131315

Verification of real-time WSA-ENLIL+Cone simulations of CME arrival-time at the CCMC/SWRC from 2010-2016

NASA Astrophysics Data System (ADS)

Wold, A. M.; Mays, M. L.; Taktakishvili, A.; Odstrcil, D.; MacNeice, P. J.; Jian, L. K.

2017-12-01

The Wang-Sheeley-Arge (WSA)-ENLIL+Cone model is used extensively in space weather operations world-wide to model CME propagation. As such, it is important to assess its performance. We present validation results of the WSA-ENLIL+Cone model installed at the Community Coordinated Modeling Center (CCMC) and executed in real-time by the CCMC/Space Weather Research Center (SWRC). CCMC/SWRC uses the WSA-ENLIL+Cone model to predict CME arrivals at NASA missions throughout the inner heliosphere. In this work we compare model predicted CME arrival-times to in-situ ICME leading edge measurements near Earth, STEREO-A and STEREO-B for simulations completed between March 2010-December 2016 (over 1,800 CMEs). We report hit, miss, false alarm, and correct rejection statistics for all three spacecraft. For all predicted CME arrivals, the hit rate is 0.5, and the false alarm rate is 0.1. For the 273 events where the CME was predicted to arrive at Earth, STEREO-A, or STEREO-B and we observed an arrival (hit), the mean absolute arrival-time prediction error was 10.4 ± 0.9 hours, with a tendency to early prediction error of -4.0 hours. We show the dependence of the arrival-time error on CME input parameters. We also explore the impact of the multi-spacecraft observations used to initialize the model CME inputs by comparing model verification results before and after the STEREO-B communication loss (since September 2014) and STEREO-A side-lobe operations (August 2014-December 2015). There is an increase of 1.7 hours in the CME arrival time error during single, or limited two-viewpoint periods, compared to the three-spacecraft viewpoint period. This trend would apply to a future space weather mission at L5 or L4 as another coronagraph viewpoint to reduce CME arrival time errors compared to a single L1 viewpoint.

The localization of guanylyl cyclase-activating proteins in the mammalian retina.

PubMed

Cuenca, N; Lopez, S; Howes, K; Kolb, H

1998-06-01

To explore the distribution of guanylyl cylase-activating proteins 1 and 2 (GCAP1 and GCAP2) in the mammalian retina. Cryostat and vibratome vertical sections and wholemount retinas from mouse, rat, cat, bovine, monkey, and human eyes were prepared for immunocytochemistry and viewing by light and confocal microscopy. In all mammalian retinas investigated, intense GCAP1 immunoreactivity (GCAP1-IR) was seen in cone photoreceptor inner and outer segments, cell bodies, and synaptic regions. Intensity of the GCAP1-IR was strong in inner segments of rods in all species but weaker in outer segments-particularly so in primates and cats. GCAP2 immunoreactivity (GCAP2-IR) was weak in bovine, mouse, and rat cones but was intense in human and monkey cones. In all species except primates, GCAP2 staining was intense in rod inner and outer segments. In primates GCAP2-IR was intense in the rod inner segment but faint in the rod outer segment. A striking difference from the GCAP1 pattern of immunoreactivity was seen with GCAP2 antibodies as far as the inner retina was concerned. GCAP2-IR was evident in certain populations of bipolar, amacrine, and ganglion cells in all species. GCAP1 and GCAP2, which are involved in Ca2+-dependent stimulation and inhibition of photoreceptor guanylyl cyclase, can be detected in mammalian photoreceptor inner and outer segments, consistent with their physiological function. The occurrence of both GCAPs in the synaptic region of the photoreceptors indicates participation of these proteins in pathways other than regulation of phototransduction. The occurrence of GCAP2 in inner retinal neurons is indicative of second-messenger chemical transduction, possibly in metabotropic glutamate, gamma-aminobutyric acid (GABA) receptor, and nitric oxide-activated neural circuits.

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

NASA Astrophysics Data System (ADS)

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

1994-08-01

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&T's CBIC-U2, 4 GHz f/sub /spl tau// 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 /spl mu/m pitch double-sided silicon strip detector. The chip measures 6.8 mm/spl times/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 10 fC signals is achieved using a time-walk compensation network. Irradiation tests at TRIUMF to a /spl Phi/=10/sup 14/ protons/cm/sup 2/ have been performed on the IC, demonstrating the radiation hardness of the complementary bipolar process.

Multiple Independent Oscillatory Networks in the Degenerating Retina

PubMed Central

Euler, Thomas; Schubert, Timm

2015-01-01

During neuronal degenerative diseases, microcircuits undergo severe structural alterations, leading to remodeling of synaptic connectivity. This can be particularly well observed in the retina, where photoreceptor degeneration triggers rewiring of connections in the retina’s first synaptic layer (e.g., Strettoi et al., 2003; Haq et al., 2014), while the synaptic organization of inner retinal circuits appears to be little affected (O’Brien et al., 2014; Figures 1A,B). Remodeling of (outer) retinal circuits and diminishing light-driven activity due to the loss of functional photoreceptors lead to spontaneous activity that can be observed at different retinal levels (Figure 1C), including the retinal ganglion cells, which display rhythmic spiking activity in the degenerative retina (Margolis et al., 2008; Stasheff, 2008; Menzler and Zeck, 2011; Stasheff et al., 2011). Two networks have been suggested to drive the oscillatory activity in the degenerating retina: a network of remnant cone photoreceptors, rod bipolar cells (RBCs) and horizontal cells in the outer retina (Haq et al., 2014), and the AII amacrine cell-cone bipolar cell network in the inner retina (Borowska et al., 2011). Notably, spontaneous rhythmic activity in the inner retinal network can be triggered in the absence of synaptic remodeling in the outer retina, for example, in the healthy retina after photo-bleaching (Menzler et al., 2014). In addition, the two networks show remarkable differences in their dominant oscillation frequency range as well as in the types and numbers of involved cells (Menzler and Zeck, 2011; Haq et al., 2014). Taken together this suggests that the two networks are self-sustained and can be active independently from each other. However, it is not known if and how they modulate each other. In this mini review, we will discuss: (i) commonalities and differences between these two oscillatory networks as well as possible interaction pathways; (ii) how multiple self-sustained networks may hamper visual restoration strategies employing, for example, microelectronic implants, optogenetics or stem cells, and briefly; and (iii) how the finding of diverse (independent) networks in the degenerative retina may relate to other parts of the neurodegenerative central nervous system. PMID:26617491

Visual and non-visual motion information processing during pursuit eye tracking in schizophrenia and bipolar disorder.

PubMed

Trillenberg, Peter; Sprenger, Andreas; Talamo, Silke; Herold, Kirsten; Helmchen, Christoph; Verleger, Rolf; Lencer, Rebekka

2017-04-01

Despite many reports on visual processing deficits in psychotic disorders, studies are needed on the integration of visual and non-visual components of eye movement control to improve the understanding of sensorimotor information processing in these disorders. Non-visual inputs to eye movement control include prediction of future target velocity from extrapolation of past visual target movement and anticipation of future target movements. It is unclear whether non-visual input is impaired in patients with schizophrenia. We recorded smooth pursuit eye movements in 21 patients with schizophrenia spectrum disorder, 22 patients with bipolar disorder, and 24 controls. In a foveo-fugal ramp task, the target was either continuously visible or was blanked during movement. We determined peak gain (measuring overall performance), initial eye acceleration (measuring visually driven pursuit), deceleration after target extinction (measuring prediction), eye velocity drifts before onset of target visibility (measuring anticipation), and residual gain during blanking intervals (measuring anticipation and prediction). In both patient groups, initial eye acceleration was decreased and the ability to adjust eye acceleration to increasing target acceleration was impaired. In contrast, neither deceleration nor eye drift velocity was reduced in patients, implying unimpaired non-visual contributions to pursuit drive. Disturbances of eye movement control in psychotic disorders appear to be a consequence of deficits in sensorimotor transformation rather than a pure failure in adding cognitive contributions to pursuit drive in higher-order cortical circuits. More generally, this deficit might reflect a fundamental imbalance between processing external input and acting according to internal preferences.

A bipolar population counter using wave pipelining to achieve 2.5 x normal clock frequency

NASA Technical Reports Server (NTRS)

Wong, Derek C.; De Micheli, Giovanni; Flynn, Michael J.; Huston, Robert E.

1992-01-01

Wave pipelining is a technique for pipelining digital systems that can increase clock frequency in practical circuits without increasing the number of storage elements. In wave pipelining, multiple coherent waves of data are sent through a block of combinational logic by applying new inputs faster than the delay through the logic. The throughput of a 63-b CML population counter was increased from 97 to 250 MHz using wave pipelining. The internal circuit is flowthrough combinational logic. Novel CAD methods have balanced all input-to-output paths to about the same delay. This allows multiple data waves to propagate in sequence when the circuit is clocked faster than its propagation delay.

Logarithmic current measurement circuit with improved accuracy and temperature stability and associated method

DOEpatents

Ericson, M. Nance; Rochelle, James M.

1994-01-01

A logarithmic current measurement circuit for operating upon an input electric signal utilizes a quad, dielectrically isolated, well-matched, monolithic bipolar transistor array. One group of circuit components within the circuit cooperate with two transistors of the array to convert the input signal logarithmically to provide a first output signal which is temperature-dependant, and another group of circuit components cooperate with the other two transistors of the array to provide a second output signal which is temperature-dependant. A divider ratios the first and second output signals to provide a resultant output signal which is independent of temperature. The method of the invention includes the operating steps performed by the measurement circuit.

Voltage mode electronically tunable full-wave rectifier

NASA Astrophysics Data System (ADS)

Petrović, Predrag B.; Vesković, Milan; Đukić, Slobodan

2017-01-01

The paper presents a new realization of bipolar full-wave rectifier of input sinusoidal signals, employing one MO-CCCII (multiple output current controlled current conveyor), a zero-crossing detector (ZCD), and one resistor connected to fixed potential. The circuit provides the operating frequency up to 10 MHz with increased linearity and precision in processing of input voltage signal, with a very low harmonic distortion. The errors related to the signal processing and errors bound were investigated and provided in the paper. The PSpice simulations are depicted and agree well with the theoretical anticipation. The maximum power consumption of the converter is approximately 2.83 mW, at ±1.2 V supply voltages.

Ribbon synapses compute temporal contrast and encode luminance in retinal rod bipolar cells

PubMed Central

Oesch, Nicholas W.; Diamond, Jeffrey S.

2011-01-01

Contrast is computed throughout the nervous system to encode changing inputs efficiently. The retina encodes luminance and contrast over a wide range of visual conditions and so must adapt its responses to maintain sensitivity and avoid saturation. Here we show how one type of adaptation allows individual synapses to compute contrast and encode luminance in biphasic responses to step changes in light levels. Light-evoked depletion of the readily releasable vesicle pool (RRP) at rod bipolar cell (RBC) ribbon synapses in rat retina limits the dynamic range available to encode transient but not sustained responses, thereby allowing the transient and sustained components of release to compute temporal contrast and encode mean light levels, respectively. A release/replenishment model shows that a single, homogeneous pool of synaptic vesicles is sufficient to generate this behavior and reveals that the dominant mechanism shaping the biphasic contrast/luminance response is the partial depletion of the RRP. PMID:22019730

A HIGH BANDWIDTH BIPOLAR POWER SUPPLY FOR THE FAST CORRECTORS IN THE APS UPGRADE*

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

Wang, Ju; Sprau, Gary

The APS Upgrade of a multi-bend achromat (MBA) storage ring requires a fast bipolar power supply for the fast correction magnets. The key performance requirement of the power supply includes a small-signal bandwidth of 10 kHz for the output current. This requirement presents a challenge to the design because of the high inductance of the magnet load and a limited input DC voltage. A prototype DC/DC power supply utilizing a MOSFET H-bridge circuit with a 500 kHz PWM has been developed and tested successfully. The prototype achieved a 10-kHz bandwidth with less than 3-dB attenuation for a signal 0.5% ofmore » the maximum operating current of 15 amperes. This paper presents the design of the power circuit, the PWM method, the control loop, and the test results.« less

Valleytronics in merging Dirac cones: All-electric-controlled valley filter, valve, and universal reversible logic gate

NASA Astrophysics Data System (ADS)

Ang, Yee Sin; Yang, Shengyuan A.; Zhang, C.; Ma, Zhongshui; Ang, L. K.

2017-12-01

Despite much anticipation of valleytronics as a candidate to replace the aging complementary metal-oxide-semiconductor (CMOS) based information processing, its progress is severely hindered by the lack of practical ways to manipulate valley polarization all electrically in an electrostatic setting. Here, we propose a class of all-electric-controlled valley filter, valve, and logic gate based on the valley-contrasting transport in a merging Dirac cones system. The central mechanism of these devices lies on the pseudospin-assisted quantum tunneling which effectively quenches the transport of one valley when its pseudospin configuration mismatches that of a gate-controlled scattering region. The valley polarization can be abruptly switched into different states and remains stable over semi-infinite gate-voltage windows. Colossal tunneling valley-pseudomagnetoresistance ratio of over 10 000 % can be achieved in a valley-valve setup. We further propose a valleytronic-based logic gate capable of covering all 16 types of two-input Boolean logics. Remarkably, the valley degree of freedom can be harnessed to resurrect logical reversibility in two-input universal Boolean gate. The (2 +1 ) polarization states (two distinct valleys plus a null polarization) reestablish one-to-one input-to-output mapping, a crucial requirement for logical reversibility, and significantly reduce the complexity of reversible circuits. Our results suggest that the synergy of valleytronics and digital logics may provide new paradigms for valleytronic-based information processing and reversible computing.

Nature's Notebook Provides Phenology Observations for NASA Juniper Phenology and Pollen Transport Project

NASA Technical Reports Server (NTRS)

Luval, J. C.; Crimmins, T. M.; Sprigg, W. A.; Levetin, E.; Huete, A.; Nickovic, S.; Prasad, A.; Vukovic, A.; VandeWater, P. K.; Budge, A. M.;

The relative effectiveness of empirical and physical models for simulating the dense undercurrent of pyroclastic flows under different emplacement conditions

USGS Publications Warehouse

Ogburn, Sarah E.; Calder, Eliza S

2017-01-01

High concentration pyroclastic density currents (PDCs) are hot avalanches of volcanic rock and gas and are among the most destructive volcanic hazards due to their speed and mobility. Mitigating the risk associated with these flows depends upon accurate forecasting of possible impacted areas, often using empirical or physical models. TITAN2D, VolcFlow, LAHARZ, and ΔH/L or energy cone models each employ different rheologies or empirical relationships and therefore differ in appropriateness of application for different types of mass flows and topographic environments. This work seeks to test different statistically- and physically-based models against a range of PDCs of different volumes, emplaced under different conditions, over different topography in order to test the relative effectiveness, operational aspects, and ultimately, the utility of each model for use in hazard assessments. The purpose of this work is not to rank models, but rather to understand the extent to which the different modeling approaches can replicate reality in certain conditions, and to explore the dynamics of PDCs themselves. In this work, these models are used to recreate the inundation areas of the dense-basal undercurrent of all 13 mapped, land-confined, Soufrière Hills Volcano dome-collapse PDCs emplaced from 1996 to 2010 to test the relative effectiveness of different computational models. Best-fit model results and their input parameters are compared with results using observation- and deposit-derived input parameters. Additional comparison is made between best-fit model results and those using empirically-derived input parameters from the FlowDat global database, which represent “forward” modeling simulations as would be completed for hazard assessment purposes. Results indicate that TITAN2D is able to reproduce inundated areas well using flux sources, although velocities are often unrealistically high. VolcFlow is also able to replicate flow runout well, but does not capture the lateral spreading in distal regions of larger-volume flows. Both models are better at reproducing the inundated area of single-pulse, valley-confined, smaller-volume flows than sustained, highly unsteady, larger-volume flows, which are often partially unchannelized. The simple rheological models of TITAN2D and VolcFlow are not able to recreate all features of these more complex flows. LAHARZ is fast to run and can give a rough approximation of inundation, but may not be appropriate for all PDCs and the designation of starting locations is difficult. The ΔH/L cone model is also very quick to run and gives reasonable approximations of runout distance, but does not inherently model flow channelization or directionality and thus unrealistically covers all interfluves. Empirically-based models like LAHARZ and ΔH/L cones can be quick, first-approximations of flow runout, provided a database of similar flows, e.g., FlowDat, is available to properly calculate coefficients or ΔH/L. For hazard assessment purposes, geophysical models like TITAN2D and VolcFlow can be useful for producing both scenario-based or probabilistic hazard maps, but must be run many times with varying input parameters. LAHARZ and ΔH/L cones can be used to produce simple modeling-based hazard maps when run with a variety of input volumes, but do not explicitly consider the probability of occurrence of different volumes. For forward modeling purposes, the ability to derive potential input parameters from global or local databases is crucial, though important input parameters for VolcFlow cannot be empirically estimated. Not only does this work provide a useful comparison of the operational aspects and behavior of various models for hazard assessment, but it also enriches conceptual understanding of the dynamics of the PDCs themselves.

Qualitative and semiquantitative Fourier transformation using a noncoherent system.

PubMed

Rogers, G L

1979-09-15

A number of authors have pointed out that a system of zone plates combined with a diffuse source, transparent input, lens, and focusing screen will display on the output screen the Fourier transform of the input. Strictly speaking, the transform normally displayed is the cosine transform, and the bipolar output is superimposed on a dc gray level to give a positive-only intensity variation. By phase-shifting one zone plate the sine transform is obtained. Temporal modulation is possible. It is also possible to redesign the system to accept a diffusely reflecting input at the cost of introducing a phase gradient in the output. Results are given of the sine and cosine transforms of a small circular aperture. As expected, the sine transform is a uniform gray. Both transforms show unwanted artifacts beyond 0.1 rad off-axis. An analysis shows this is due to unwanted circularly symmetrical moire patterns between the zone plates.

Quantification of color vision using a tablet display.

PubMed

Chacon, Alicia; Rabin, Jeff; Yu, Dennis; Johnston, Shawn; Bradshaw, Timothy

2015-01-01

Accurate color vision is essential for optimal performance in aviation and space environments using nonredundant color coding to convey critical information. Most color tests detect color vision deficiency (CVD) but fail to diagnose type or severity of CVD, which are important to link performance to occupational demands. The computer-based Cone Contrast Test (CCT) diagnoses type and severity of CVD. It is displayed on a netbook computer for clinical application, but a more portable version may prove useful for deployments, space and aviation cockpits, as well as accident and sports medicine settings. Our purpose was to determine if the CCT can be conducted on a tablet display (Windows 8, Microsoft, Seattle, WA) using touch-screen response input. The CCT presents colored letters visible only to red (R), green (G), and blue (B) sensitive retinal cones to determine the lowest R, G, and B cone contrast visible to the observer. The CCT was measured in 16 color vision normals (CVN) and 16 CVDs using the standard netbook computer and a Windows 8 tablet display calibrated to produce equal color contrasts. Both displays showed 100% specificity for confirming CVN and 100% sensitivity for detecting CVD. In CVNs there was no difference between scores on netbook vs. tablet displays. G cone CVDs showed slightly lower G cone CCT scores on the tablet. CVD can be diagnosed with a tablet display. Ease-of-use, portability, and complete computer capabilities make tablets ideal for multiple settings, including aviation, space, military deployments, accidents and rescue missions, and sports vision. Chacon A, Rabin J, Yu D, Johnston S, Bradshaw T. Quantification of color vision using a tablet display.

Lifestyle interventions targeting dietary habits and exercise in bipolar disorder: A systematic review.

PubMed

Bauer, Isabelle E; Gálvez, Juan F; Hamilton, Jane E; Balanzá-Martínez, Vicent; Zunta-Soares, Giovana B; Soares, Jair C; Meyer, Thomas D

2016-03-01

Bipolar disorder (BD) is a serious mental illness associated with a high risk of medical comorbidities, long-term disability and premature death. This systematic review examined the current literature on therapeutic interventions targeting nutrition, physical activity and wellness in BD and collecting health-related measures such as mood and course of illness. Scopus (all databases), Pubmed and Ovid Medline were systematically searched with no language or year restrictions, up to June 2015, for studies focusing on lifestyle interventions in BD. Search terms were related to bipolar disorder, nutrition, physical activity, wellbeing, psychosocial interventions and course of illness. We hand searched content pages of Bipolar Disorders and Journal of Affective Disorders and checked references of relevant reviews and dissertations to identify additional papers. After applying inclusion and exclusion criteria to identified hits, this literature search retrieved six papers. Overall findings point towards a beneficial role of lifestyle interventions on mood, weight, blood pressure, lipid profile, physical activity and overall wellbeing. Methodological limitations include small sample size, gender ratio imbalance, inconsistencies in terms of laboratory measures, and lack of randomized controlled trials and absence of follow-up and longitudinal studies to determine the benefits of these factors on clinical and functional outcomes over time Lifestyle interventions in BD targeting nutrition, exercise, wellbeing alongside beliefs, coping strategies and attitudes towards health show promise in reducing the risk of comorbid ailments in BD. There is still a strong need for studies a) developing interventions which are informed by the patient's input and b) examining the effectiveness of such interventions targeting general wellness using well-controlled trials. Published by Elsevier Ltd.

Real­-Time Ensemble Forecasting of Coronal Mass Ejections Using the Wsa-Enlil+Cone Model

NASA Astrophysics Data System (ADS)

Mays, M. L.; Taktakishvili, A.; Pulkkinen, A. A.; Odstrcil, D.; MacNeice, P. J.; Rastaetter, L.; LaSota, J. A.

2014-12-01

Ensemble forecasting of coronal mass ejections (CMEs) provides significant information in that it provides an estimation of the spread or uncertainty in CME arrival time predictions. Real-time ensemble modeling of CME propagation is performed by forecasters at the Space Weather Research Center (SWRC) using the WSA-ENLIL+cone model available at the Community Coordinated Modeling Center (CCMC). To estimate the effect of uncertainties in determining CME input parameters on arrival time predictions, a distribution of n (routinely n=48) CME input parameter sets are generated using the CCMC Stereo CME Analysis Tool (StereoCAT) which employs geometrical triangulation techniques. These input parameters are used to perform n different simulations yielding an ensemble of solar wind parameters at various locations of interest, including a probability distribution of CME arrival times (for hits), and geomagnetic storm strength (for Earth-directed hits). We present the results of ensemble simulations for a total of 38 CME events in 2013-2014. For 28 of the ensemble runs containing hits, the observed CME arrival was within the range of ensemble arrival time predictions for 14 runs (half). The average arrival time prediction was computed for each of the 28 ensembles predicting hits and using the actual arrival time, an average absolute error of 10.0 hours (RMSE=11.4 hours) was found for all 28 ensembles, which is comparable to current forecasting errors. Some considerations for the accuracy of ensemble CME arrival time predictions include the importance of the initial distribution of CME input parameters, particularly the mean and spread. When the observed arrivals are not within the predicted range, this still allows the ruling out of prediction errors caused by tested CME input parameters. Prediction errors can also arise from ambient model parameters such as the accuracy of the solar wind background, and other limitations. Additionally the ensemble modeling sysem was used to complete a parametric event case study of the sensitivity of the CME arrival time prediction to free parameters for ambient solar wind model and CME. The parameter sensitivity study suggests future directions for the system, such as running ensembles using various magnetogram inputs to the WSA model.

Spin stability of sounding rocket secondary payloads following high velocity ejections

NASA Astrophysics Data System (ADS)

Nelson, Weston M.

The Auroral Spatial Structures Probe (ASSP) mission is a sounding rocket mission studying solar energy input to space weather. ASSP requires the high velocity ejection (up to 50 m/s) of 6 secondary payloads, spin stabilized perpendicular to the ejection velocity. The proposed scientific instrumentation depends on a high degree of spin stability, requiring a maximum coning angle of less than 5°. It also requires that the spin axis be aligned within 25° of the local magnetic field lines. The maximum velocities of current ejection methods are typically less than 10m/s, and often produce coning angles in excess of 20°. Because of this they do not meet the ASSP mission requirements. To meet these requirements a new ejection method is being developed by NASA Wallops Flight Facility. Success of the technique in meeting coning angle and B-field alignment requirements is evaluated herein by modeling secondary payload dynamic behavior using a 6-DOF dynamic simulation employing state space integration written in MATLAB. Simulation results showed that secondary payload mass balancing is the most important factor in meeting stability requirements. Secondary mass payload properties will be measured using an inverted torsion pendulum. If moment of inertia measurement errors can be reduced to 0.5%, it is possible to achieve mean coning and B-field alignment angles of 2.16° and 2.71°, respectively.

A Cre Mouse Line for Probing Irradiance- and Direction-Encoding Retinal Networks

PubMed Central

Sabbah, Shai

2017-01-01

Abstract Cell type-specific Cre driver lines have revolutionized the analysis of retinal cell types and circuits. We show that the transgenic mouse Rbp4-Cre selectively labels several retinal neuronal types relevant to the encoding of absolute light intensity (irradiance) and visual motion. In the ganglion cell layer (GCL), most marked cells are wide-field spiking polyaxonal amacrine cells (ACs) with sustained irradiance-encoding ON responses that persist during chemical synaptic blockade. Their arbors spread about 1 mm across the retina and are restricted to the inner half of the ON sublamina of the inner plexiform layer (IPL). There, they costratify with dendrites of M2 intrinsically photosensitive retinal ganglion cells (ipRGCs), to which they are tracer coupled. We propose that synaptically driven and intrinsic photocurrents of M2 cells pass through gap junctions to drive AC light responses. Also marked in this mouse are two types of RGCs. R-cells have a bistratified dendritic arbor, weak directional tuning, and irradiance-encoding ON responses. However, they also receive excitatory OFF input, revealed during ON-channel blockade. Serial blockface electron microscopic (SBEM) reconstruction confirms OFF bipolar input, and reveals that some OFF input derives from a novel type of OFF bipolar cell (BC). R-cells innervate specific layers of the dorsal lateral geniculate nucleus (dLGN) and superior colliculus (SC). The other marked RGC type (RDS) is bistratified, transient, and ON-OFF direction selective (DS). It apparently innervates the nucleus of the optic tract (NOT). The Rbp4-Cre mouse will be valuable for targeting these cell types for further study and for selectively manipulating them for circuit analysis. PMID:28466070

Data acquisition channel apparatus

NASA Astrophysics Data System (ADS)

Higgins, C. H.; Skipper, J. D.

1985-10-01

Dicussed is a hybrid integrated circuit data acquisition channel apparatus employing an operational amplifier fed by a low current differential bipolar transistor preamplifier having separate feedback gain and signal gain determining elements and providing an amplified signal output to a sample and hold and analog-to-digital converter circuits. The disclosed apparatus operates with low energy and small space requirements and is capable of operations without the sample and hold circuit where the nature of the applied input signal permits.

A rugged 650 V SOI-based high-voltage half-bridge IGBT gate driver IC for motor drive applications

NASA Astrophysics Data System (ADS)

Hua, Qing; Li, Zehong; Zhang, Bo; Chen, Weizhong; Huang, Xiangjun; Feng, Yuxiang

2015-05-01

This paper proposes a rugged high-voltage N-channel insulated gate bipolar transistor (IGBT) gate driver integrated circuit. The device integrates a high-side and a low-side output stages on a single chip, which is designed specifically for motor drive applications. High-voltage level shift technology enables the high-side stage of this device to operate up to 650 V. The logic inputs are complementary metal oxide semiconductor (CMOS)/transistor transistor logic compatible down to 3.3 V. Undervoltage protection functionality with hysteresis characteristic has also been integrated to enhance the device reliability. The device is fabricated in a 1.0 μm, 650 V high-voltage bipolar CMOS double-diffused metal oxide semiconductor (BCD) on silicon-on-insulator (SOI) process. Deep trench dielectric isolation technology is employed to provide complete electrical isolation with advantages such as reduced parasitic effects, excellent noise immunity and low leakage current. Experimental results show that the isolation voltage of this device can be up to approximately 779 V at 25°C, and the leakage current is only 5 nA at 650 V, which is 15% higher and 67% lower than the conventional ones. In addition, it delivers an excellent thermal stability and needs very low quiescent current and offers a high gate driver capability which is needed to adequately drive IGBTs that have large input capacitances.

Verification of real-time WSA-ENLIL+Cone simulations of CME arrival-time at the CCMC from 2010 to 2016

NASA Astrophysics Data System (ADS)

Wold, Alexandra M.; Mays, M. Leila; Taktakishvili, Aleksandre; Jian, Lan K.; Odstrcil, Dusan; MacNeice, Peter

2018-03-01

The Wang-Sheeley-Arge (WSA)-ENLIL+Cone model is used extensively in space weather operations world-wide to model coronal mass ejection (CME) propagation. As such, it is important to assess its performance. We present validation results of the WSA-ENLIL+Cone model installed at the Community Coordinated Modeling Center (CCMC) and executed in real-time by the CCMC space weather team. CCMC uses the WSA-ENLIL+Cone model to predict CME arrivals at NASA missions throughout the inner heliosphere. In this work we compare model predicted CME arrival-times to in situ interplanetary coronal mass ejection leading edge measurements at Solar TErrestrial RElations Observatory-Ahead (STEREO-A), Solar TErrestrial RElations Observatory-Behind (STEREO-B), and Earth (Wind and ACE) for simulations completed between March 2010 and December 2016 (over 1,800 CMEs). We report hit, miss, false alarm, and correct rejection statistics for all three locations. For all predicted CME arrivals, the hit rate is 0.5, and the false alarm rate is 0.1. For the 273 events where the CME was predicted to arrive at Earth, STEREO-A, or STEREO-B, and was actually observed (hit event), the mean absolute arrival-time prediction error was 10.4 ± 0.9 h, with a tendency to early prediction error of -4.0 h. We show the dependence of the arrival-time error on CME input parameters. We also explore the impact of the multi-spacecraft observations used to initialize the model CME inputs by comparing model verification results before and after the STEREO-B communication loss (since September 2014) and STEREO-A sidelobe operations (August 2014-December 2015). There is an increase of 1.7 h in the CME arrival time error during single, or limited two-viewpoint periods, compared to the three-spacecraft viewpoint period. This trend would apply to a future space weather mission at L5 or L4 as another coronagraph viewpoint to reduce CME arrival time errors compared to a single L1 viewpoint.

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

PubMed

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.

Traveling wave linear accelerator with RF power flow outside of accelerating cavities

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

Dolgashev, Valery A.

A high power RF traveling wave accelerator structure includes a symmetric RF feed, an input matching cell coupled to the symmetric RF feed, a sequence of regular accelerating cavities coupled to the input matching cell at an input beam pipe end of the sequence, one or more waveguides parallel to and coupled to the sequence of regular accelerating cavities, an output matching cell coupled to the sequence of regular accelerating cavities at an output beam pipe end of the sequence, and output waveguide circuit or RF loads coupled to the output matching cell. Each of the regular accelerating cavities hasmore » a nose cone that cuts off field propagating into the beam pipe and therefore all power flows in a traveling wave along the structure in the waveguide.« less

Modeling intrinsic electrophysiology of AII amacrine cells: preliminary results.

PubMed

Apollo, Nick; Grayden, David B; Burkitt, Anthony N; Meffin, Hamish; Kameneva, Tatiana

2013-01-01

In patients who have lost their photoreceptors due to retinal degenerative diseases, it is possible to restore rudimentary vision by electrically stimulating surviving neurons. AII amacrine cells, which reside in the inner plexiform layer, split the signal from rod bipolar cells into ON and OFF cone pathways. As a result, it is of interest to develop a computational model to aid in the understanding of how these cells respond to the electrical stimulation delivered by a prosthetic implant. The aim of this work is to develop and constrain parameters in a single-compartment model of an AII amacrine cell using data from whole-cell patch clamp recordings. This model will be used to explore responses of AII amacrine cells to electrical stimulation. Single-compartment Hodgkin-Huxley-type neural models are simulated in the NEURON environment. Simulations showed successful reproduction of the potassium currentvoltage relationship and some of the spiking properties observed in vitro.

Calculation of inviscid surface streamlines and heat transfer on shuttle type configurations. Part 2: Description of computer program

NASA Technical Reports Server (NTRS)

Dejarnette, F. R.; Jones, M. H.

1971-01-01

A description of the computer program used for heating rate calculation for blunt bodies in hypersonic flow is given. The main program and each subprogram are described by defining the pertinent symbols involved and presenting a detailed flow diagram and complete computer program listing. Input and output parameters are discussed in detail. Listings are given for the computation of heating rates on (1) a blunted 15 deg half-angle cone at 20 deg incidence and Mach 10.6, (2) a blunted 70 deg slab delta wing at 10 deg incidence and Mach 8, and (3) the HL-10 lifting body at 20 deg incidence and Mach 10. In addition, the computer program output for two streamlines on the blunted 15 deg half-angle cone is listed. For Part 1, see N71-36186.

CME Arrival-time Validation of Real-time WSA-ENLIL+Cone Simulations at the CCMC/SWRC

NASA Astrophysics Data System (ADS)

Wold, A. M.; Mays, M. L.; Taktakishvili, A.; Jian, L.; Odstrcil, D.; MacNeice, P. J.

2016-12-01

The Wang-Sheeley-Arge (WSA)-ENLIL+Cone model is used extensively in space weather operations worldwide to model CME propagation, as such it is important to assess its performance. We present validation results of the WSA-ENLIL+Cone model installed at the Community Coordinated Modeling Center (CCMC) and executed in real-time by the CCMC/Space Weather Research Center (SWRC). The SWRC is a CCMC sub-team that provides space weather services to NASA robotic mission operators and science campaigns, and also prototypes new forecasting models and techniques. CCMC/SWRC uses the WSA-ENLIL+Cone model to predict CME arrivals at NASA missions throughout the inner heliosphere. In this work we compare model predicted CME arrival-times to in-situ ICME shock observations near Earth (ACE, Wind), STEREO-A and B for simulations completed between March 2010 - July 2016 (over 1500 runs). We report hit, miss, false alarm, and correct rejection statistics for all three spacecraft. For hits we compute the bias, RMSE, and average absolute CME arrival time error, and the dependence of these errors on CME input parameters. We compare the predicted geomagnetic storm strength (Kp index) to the CME arrival time error for Earth-directed CMEs. The predicted Kp index is computed using the WSA-ENLIL+Cone plasma parameters at Earth with a modified Newell et al. (2007) coupling function. We also explore the impact of the multi-spacecraft observations on the CME parameters used initialize the model by comparing model validation results before and after the STEREO-B communication loss (since September 2014) and STEREO-A side-lobe operations (August 2014-December 2015). This model validation exercise has significance for future space weather mission planning such as L5 missions.

Acid-base chemistry and aluminum transport in an acidic watershed and pond in New Hampshire

Treesearch

Scott W. Bailey; Charles T. Driscoll; James W. Hornbeck

1995-01-01

Cone Pond is one of the few acidic, clear-water ponds in the White Mountains of New Hampshire, a region dominated by high inputs of strong acids from atmospheric deposition and low base content of bedrock. Monitoring was conducted for 13 months to compare and contrast the acid-base chemistry of the terrestrial and aquatic portions of the watershed. Variations in Al...

The temporal characteristics of the early and late stages of the L- and M-cone pathways that signal color

PubMed Central

Petrova, Daniela; Henning, G. Bruce; Stockman, Andrew

2013-01-01

Flickering long-wavelength light appears more yellow than steady light of the same average intensity. The hue change is consistent with distortion of the visual signal at some nonlinear site (or sites) that produces temporal components not present in the original stimulus (known as distortion products). We extracted the temporal attenuation characteristics of the early (prenonlinearity) and late (post-nonlinearity) filter stages in the L- and M-cone chromatic pathway by varying the input stimulus to manipulate the distortion products and the measuring of the observers' sensitivity to them. The early, linear, filter stage acts like a band-pass filter peaking at 10–15 Hz with substantial sensitivity losses at both lower and higher frequencies. Its characteristics are consistent with nonlinearity being early in the visual pathway but following surround inhibition. The late stage, in contrast, acts like a low-pass filter with a cutoff frequency around 3 Hz. The response of the early stage speeds up with radiance, but the late stage does not. A plausible site for the nonlinearity, which modelling suggests may be smoothly compressive but with a hard limit at high input levels, is after surround inhibition from the horizontal cells. PMID:23457358

Characterization of Modified Tapioca Starch Solutions and Their Sprays for High Temperature Coating Applications

PubMed Central

Naz, M. Y.; Sulaiman, S. A.; Ariwahjoedi, B.; Shaari, Ku Zilati Ku

2014-01-01

The objective of the research was to understand and improve the unusual physical and atomization properties of the complexes/adhesives derived from the tapioca starch by addition of borate and urea. The characterization of physical properties of the synthesized adhesives was carried out by determining the effect of temperature, shear rate, and mass concentration of thickener/stabilizer on the complex viscosity, density, and surface tension. In later stage, phenomenological analyses of spray jet breakup of heated complexes were performed in still air. Using a high speed digital camera, the jet breakup dynamics were visualized as a function of the system input parameters. The further analysis of the grabbed images confirmed the strong influence of the input processing parameters on full cone spray patternation. It was also predicted that the heated starch adhesive solutions generate a dispersed spray pattern by utilizing the partial evaporation of the spraying medium. Below 40°C of heating temperature, the radial spray cone width and angle did not vary significantly with increasing Reynolds and Weber numbers at early injection phases leading to increased macroscopic spray propagation. The discharge coefficient, mean flow rate, and mean flow velocity were significantly influenced by the load pressure but less affected by the temperature. PMID:24592165

Toluene Inhalation Exposure for 13 Weeks Causes Persistent Changes in Electroretinograms of Long-Evans Rats

PubMed Central

Boyes, William K.; Bercegeay, Mark; Degn, Laura; Beasley, Tracey E.; Evansky, Paul A.; Mwanza, Jean Claude; Geller, Andrew M.; Pinckney, Charles; Nork, T. Michael; Bushnell, Philip J.

2016-01-01

Studies of humans chronically exposed to volatile organic solvents have reported impaired visual functions, including low contrast sensitivity and reduced color discrimination. These reports, however, lacked confirmation from controlled laboratory experiments. To address this question experimentally, we examined visual function by recording visual evoked potentials (VEP) and/or electroretinograms (ERG) from four sets of rats exposed repeatedly to toluene. In addition, eyes of the rats were examined with an ophthalmoscope and some of the retinal tissues were evaluated for rod and M-cone photoreceptor immunohistochemistry. The first study examined rats following exposure to 0, 10, 100 or 1000 ppm toluene by inhalation (6 hr/d, 5 d/wk) for 13 weeks. One week after the termination of exposure, the rats were implanted with chronically indwelling electrodes and the following week pattern-elicited VEPs were recorded. VEP amplitudes were not significantly changed by toluene exposure. Four to five weeks after completion of exposure, rats were dark-adapted overnight, anesthetized, and several sets of electroretinograms (ERG) were recorded. In dark-adapted ERGs recorded over a 5-log (cd-s/m2) range of flash luminance, b-wave amplitudes were significantly reduced at high stimulus luminance values in rats previously exposed to 1000 ppm toluene. A second set of rats, exposed concurrently with the first set, was tested approximately one year after the termination of 13 weeks of exposure to toluene. Again, dark-adapted ERG b-wave amplitudes were reduced at high stimulus luminance values in rats previously exposed to 1000 ppm toluene. A third set of rats was exposed to the same concentrations of toluene for only 4 weeks, and a fourth set of rats exposed to 0 or 1000 ppm toluene for 4 weeks were tested approximately 1 year after the completion of exposure. No statistically significant reductions of ERG b-wave amplitude were observed in either set of rats exposed for 4 weeks. No significant changes were observed in ERG a-wave amplitude or latency, b-wave latency, UV- or green-flicker ERGs, or in photopic flash ERGs. There were no changes in the density of rod or M-cone photoreceptors. The ERG b-wave reflects the firing patterns of on-bipolar cells. The reductions of b-wave amplitude after 13 weeks of exposure and persisting for 1 year suggest that alterations may have occurred in the inner nuclear layer of the retina, where the bipolar cells reside, or the outer or inner plexiform layers where the bipolar cells make synaptic connections. These data provide experimental evidence that repeated exposure to toluene may lead to subtle persistent changes in visual function. The fact that toluene affected ERGs, but not VEPs, suggests that elements in the rat retina may be more sensitive to organic solvent exposure than the rat visual cortex. PMID:26899397

Optical implementation of systolic array processing

NASA Technical Reports Server (NTRS)

Caulfield, H. J.; Rhodes, W. T.; Foster, M. J.; Horvitz, S.

1981-01-01

Algorithms for matrix vector multiplication are implemented using acousto-optic cells for multiplication and input data transfer and using charge coupled devices detector arrays for accumulation and output of the results. No two dimensional matrix mask is required; matrix changes are implemented electronically. A system for multiplying a 50 component nonnegative real vector by a 50 by 50 nonnegative real matrix is described. Modifications for bipolar real and complex valued processing are possible, as are extensions to matrix-matrix multiplication and multiplication of a vector by multiple matrices.

Software Aids In Graphical Depiction Of Flow Data

NASA Technical Reports Server (NTRS)

Stegeman, J. D.

1995-01-01

Interactive Data Display System (IDDS) computer program is graphical-display program designed to assist in visualization of three-dimensional flow in turbomachinery. Grid and simulation data files in PLOT3D format required for input. Able to unwrap volumetric data cone associated with centrifugal compressor and display results in easy-to-understand two- or three-dimensional plots. IDDS provides majority of visualization and analysis capability for Integrated Computational Fluid Dynamics and Experiment (ICE) system. IDDS invoked from any subsystem, or used as stand-alone package of display software. Generates contour, vector, shaded, x-y, and carpet plots. Written in C language. Input file format used by IDDS is that of PLOT3D (COSMIC item ARC-12782).

Immunocytochemical localization of three vesicular glutamate transporters in the cat retina.

PubMed

Fyk-Kolodziej, Bozena; Dzhagaryan, Arturik; Qin, Pu; Pourcho, Roberta G

2004-08-02

Vesicular transporters play an essential role in the packaging of glutamate for synaptic release and so are of particular importance in the retina, where glutamate serves as the neurotransmitter for photoreceptors, bipolar cells, and ganglion cells. In the present study, we have examined the distribution of the three known isoforms of vesicular glutamate transporter (VGLUT) in the cat retina. VGLUT1 was localized to all photoreceptor and bipolar cells, whereas VGLUT2 was found in ganglion cells. This basic pattern of complementary distribution for the two transporters among known populations of glutamatergic cells is similar to previous findings in the brain and spinal cord. However, the axon terminals of S-cone photoreceptors were found to express both VGLUT1 and VGLUT2 and some ganglion cells labeled for both VGLUT2 and VGLUT3. Such colocalizations suggest the existence of dual modes of regulation of vesicular glutamate transport in these neurons. Staining for VGLUT2 was also present in a small number of varicose processes, which were seen to ramify throughout the inner plexiform layer. These fibers may represent axon collaterals of ganglion cells. The most prominent site of VGLUT3 immunoreactivity was in a population of amacrine cells; the axon terminals of B-type horizontal cells were also labeled at their contacts with rod spherules. The presence of the VGLUT3 transporter at sites not otherwise implicated in glutamate release may indicate novel modes of glutamate signaling or additional roles for the transporter molecule. Copyright 2004 Wiley-Liss, Inc.

Lifestyle interventions targeting dietary habits and exercise in bipolar disorder: a systematic review

PubMed Central

BAUER, ISABELLE E.; GÁLVEZ, JUAN F.; HAMILTON, JANE E.; BALANZÁ-MARTÍNEZ, VICENT; ZUNTA-SOARES, GIOVANA; SOARES, JAIR C.; MEYER, THOMAS D.

2015-01-01

Background Bipolar disorder (BD) is a serious mental illness associated with a high risk of medical comorbidities, long-term disability and premature death. This systematic review examined the current literature on therapeutic interventions targeting nutrition and physical activity in BD and collecting health-related measures such as mood and course of illness. Methods Scopus (all databases), Pubmed and Ovid Medline were systematically searched with no language or year restrictions, up to June 2015, for studies focusing on lifestyle interventions in BD. Search terms were related to bipolar disorder, nutrition, physical activity, wellbeing, psychosocial interventions and course of illness. We hand searched content pages of Bipolar Disorders and Journal of Affective Disorders and checked references of relevant reviews and dissertations to identify additional papers. Results After applying inclusion and exclusion criteria to identified hits, this literature search retrieved six papers. Overall findings point towards a beneficial role of lifestyle interventions on mood, weight, blood pressure, lipid profile, physical activity and overall wellbeing. Methodological limitations include small sample size, gender ratio imbalance, inconsistencies in terms of laboratory measures, and lack of randomized control trials and absence of follow-up and longitudinal studies to determine the benefits of these factors on clinical and functional outcomes over time Conclusions Lifestyle interventions in BD targeting nutrition, exercise, wellbeing alongside beliefs, coping strategies and attitudes towards health show promise in reducing the risk of comorbid ailments in BD. There is still a strong need for studies a) developing interventions which are informed by the patient’s input and b) examining the effectiveness of such interventions targeting general wellness using well-controlled trials. PMID:26724541

Retinal findings in a patient of French ancestry with CABP4-related retinal disease.

PubMed

Smirnov, Vasily Mikhaïlovitch; Zeitz, Christina; Soumittra, Nagasamy; Audo, Isabelle; Defoort-Dhellemmes, Sabine

2018-04-01

CABP4-related retinal dysfunction is a cone-rod synaptic transmission disorder with electronegative electroretinogram (ERG) waveform. It is a rare retinal dysfunction that can be classified into the incomplete form of congenital stationary night blindness. Absent foveal reflex and overall foveal thinning were previously reported, but in most cases the fundus appearance was described as nearly normal. We report here peculiar macular changes in a patient of French ancestry harbouring CABP4 mutations. Complete ocular examination and full-field ERG were performed at the initial presentation and follow-up. Multimodal fundus imagining, including spectral-domain optical coherence tomography, colour, infrared reflectance and short-wavelength autofluorescence photographs, was performed during follow-up visits. A 7-month-old infant was addressed to our department for visual unresponsiveness and nystagmus. ERG had an electronegative waveform, even for light-adapted stimuli, thus supporting the diagnosis of photoreceptor-bipolar cell transmission disorder. Genetic investigations discovered a compound heterozygous mutation in CABP4: c.646C > T, p.Arg216*/c.673C > T, p.Arg225*. Multimodal fundus imaging, performed at follow-up visits, showed fine radial folds at the vitreomacular interface and dark foveal dots in both eyes. Optic coherence tomography revealed a focal foveal ellipsoid zone gap. Initial presentation was misleading with Leber congenital amaurosis. The electronegative ERG waveform reoriented the genetic investigations and thus establishing a correct diagnosis. To the best of our knowledge, the peculiar fundus changes observed in our patient were never reported before. We hypothesized that a foveal ellipsoid zone interruption discovered in our patient could reflect mostly a cone dysfunction. It was unclear whether the fine radial folds in both maculae were linked with high hyperopia or were an intrinsic feature of the retinal disease. CABP4-related retinal disease is a cone-rod system disorder with possible foveal abnormalities.

Development and Evaluation of a Smartphone-Based Measure of Social Rhythms for Bipolar Disorder.

PubMed

Matthews, Mark; Abdullah, Saeed; Murnane, Elizabeth; Voida, Stephen; Choudhury, Tanzeem; Gay, Geri; Frank, Ellen

2016-08-01

Dynamic psychological processes are most often assessed using self-report instruments. This places a constraint on how often and for how long data can be collected due to the burden placed on human participants. Smartphones are ubiquitous and highly personal devices, equipped with sensors that offer an opportunity to measure and understand psychological processes in real-world contexts over the long term. In this article, we present a novel smartphone approach to address the limitations of self-report in bipolar disorder where mood and activity are key constructs. We describe the development of MoodRhythm, a smartphone application that incorporates existing self-report elements from interpersonal and social rhythm therapy, a clinically validated treatment, and combines them with novel inputs from smartphone sensors. We reflect on lessons learned in transitioning from an existing self-report instrument to one that involves smartphone sensors and discuss the potential impact of these changes on the future of psychological assessment.

Novel transformation-based response prediction of shear building using interval neural network

NASA Astrophysics Data System (ADS)

Chakraverty, S.; Sahoo, Deepti Moyi

2017-04-01

Present paper uses powerful technique of interval neural network (INN) to simulate and estimate structural response of multi-storey shear buildings subject to earthquake motion. The INN is first trained for a real earthquake data, viz., the ground acceleration as input and the numerically generated responses of different floors of multi-storey buildings as output. Till date, no model exists to handle positive and negative data in the INN. As such here, the bipolar data in [ -1, 1] are converted first to unipolar form, i.e., to [0, 1] by means of a novel transformation for the first time to handle the above training patterns in normalized form. Once the training is done, again the unipolar data are converted back to its bipolar form by using the inverse transformation. The trained INN architecture is then used to simulate and test the structural response of different floors for various intensity earthquake data and it is found that the predicted responses given by INN model are good for practical purposes.

Reliability testing of ultra-low noise InGaAs quad photoreceivers

NASA Astrophysics Data System (ADS)

Joshi, Abhay M.; Datta, Shubhashish; Prasad, Narasimha; Sivertz, Michael

2018-02-01

We have developed ultra-low noise quadrant InGaAs photoreceivers for multiple applications ranging from Laser Interferometric Gravitional Wave Detection, to 3D Wind Profiling. Devices with diameters of 0.5 mm, 1mm, and 2 mm were processed, with the nominal capacitance of a single quadrant of a 1 mm quad photodiode being 2.5 pF. The 1 mm diameter InGaAs quad photoreceivers, using a low-noise, bipolar-input OpAmp circuitry exhibit an equivalent input noise per quadrant of <1.7 pA/√Hz in 2 to 20 MHz frequency range. The InGaAs Quad Photoreceivers have undergone the following reliability tests: 30 MeV Proton Radiation up to a Total Ionizing Dose (TID) of 50 krad, Mechanical Shock, and Sinusoidal Vibration.

Single-Event Transient Response of Comparator Pre-Amplifiers in a Complementary SiGe Technology

NASA Astrophysics Data System (ADS)

Ildefonso, Adrian; Lourenco, Nelson E.; Fleetwood, Zachary E.; Wachter, Mason T.; Tzintzarov, George N.; Cardoso, Adilson S.; Roche, Nicolas J.-H.; Khachatrian, Ani; McMorrow, Dale; Buchner, Stephen P.; Warner, Jeffrey H.; Paki, Pauline; Kaynak, Mehmet; Tillack, Bernd; Cressler, John D.

2017-01-01

The single-event transient (SET) response of the pre-amplification stage of two latched comparators designed using either npn or pnp silicon-germanium heterojunction bipolar transistors (SiGe HBTs) is investigated via two-photon absorption (TPA) carrier injection and mixed-mode TCAD simulations. Experimental data and TCAD simulations showed an improved SET response for the pnp comparator circuit. 2-D raster scans revealed that the devices in the pnp circuit exhibit a reduction in sensitive area of up to 80% compared to their npn counterparts. In addition, by sweeping the input voltage, the sensitive operating region with respect to SETs was determined. By establishing a figure-of-merit, relating the transient peaks and input voltage polarities, the pnp device was determined to have a 21.4% improved response with respect to input voltage. This study has shown that using pnp devices is an effective way to mitigate SETs, and could enable further radiation-hardening-by-design techniques.

Achromatic vector vortex beams from a glass cone

PubMed Central

Radwell, N.; Hawley, R. D.; Götte, J. B.; Franke-Arnold, S.

2016-01-01

The reflection of light is governed by the laws first described by Augustin-Jean Fresnel: on internal reflection, light acquires a phase shift, which depends on its polarization direction with respect to the plane of incidence. For a conical reflector, the cylindrical symmetry is echoed in an angular variation of this phase shift, allowing us to create light modes with phase and polarization singularities. Here we observe the phase and polarization profiles of light that is back reflected from a solid glass cone and, in the case of circular input light, discover that not only does the beam contain orbital angular momentum but can trivially be converted to a radially polarized beam. Importantly, the Fresnel coefficients are reasonably stable across the visible spectrum, which we demonstrate by measuring white light polarization profiles. This discovery provides a highly cost-effective technique for the generation of broadband orbital angular momentum and radially polarized beams. PMID:26861191

Estimation of absorbed doses from paediatric cone-beam CT scans: MOSFET measurements and Monte Carlo simulations.

PubMed

Kim, Sangroh; Yoshizumi, Terry T; Toncheva, Greta; Frush, Donald P; Yin, Fang-Fang

2010-03-01

The purpose of this study was to establish a dose estimation tool with Monte Carlo (MC) simulations. A 5-y-old paediatric anthropomorphic phantom was computed tomography (CT) scanned to create a voxelised phantom and used as an input for the abdominal cone-beam CT in a BEAMnrc/EGSnrc MC system. An X-ray tube model of the Varian On-Board Imager((R)) was built in the MC system. To validate the model, the absorbed doses at each organ location for standard-dose and low-dose modes were measured in the physical phantom with MOSFET detectors; effective doses were also calculated. In the results, the MC simulations were comparable to the MOSFET measurements. This voxelised phantom approach could produce a more accurate dose estimation than the stylised phantom method. This model can be easily applied to multi-detector CT dosimetry.

Imaging light responses of foveal ganglion cells in the living macaque eye.

PubMed

Yin, Lu; Masella, Benjamin; Dalkara, Deniz; Zhang, Jie; Flannery, John G; Schaffer, David V; Williams, David R; Merigan, William H

2014-05-07

The fovea dominates primate vision, and its anatomy and perceptual abilities are well studied, but its physiology has been little explored because of limitations of current physiological methods. In this study, we adapted a novel in vivo imaging method, originally developed in mouse retina, to explore foveal physiology in the macaque, which permits the repeated imaging of the functional response of many retinal ganglion cells (RGCs) simultaneously. A genetically encoded calcium indicator, G-CaMP5, was inserted into foveal RGCs, followed by calcium imaging of the displacement of foveal RGCs from their receptive fields, and their intensity-response functions. The spatial offset of foveal RGCs from their cone inputs makes this method especially appropriate for fovea by permitting imaging of RGC responses without excessive light adaptation of cones. This new method will permit the tracking of visual development, progression of retinal disease, or therapeutic interventions, such as insertion of visual prostheses.

Achromatic vector vortex beams from a glass cone

NASA Astrophysics Data System (ADS)

Radwell, N.; Hawley, R. D.; Götte, J. B.; Franke-Arnold, S.

2016-02-01

The reflection of light is governed by the laws first described by Augustin-Jean Fresnel: on internal reflection, light acquires a phase shift, which depends on its polarization direction with respect to the plane of incidence. For a conical reflector, the cylindrical symmetry is echoed in an angular variation of this phase shift, allowing us to create light modes with phase and polarization singularities. Here we observe the phase and polarization profiles of light that is back reflected from a solid glass cone and, in the case of circular input light, discover that not only does the beam contain orbital angular momentum but can trivially be converted to a radially polarized beam. Importantly, the Fresnel coefficients are reasonably stable across the visible spectrum, which we demonstrate by measuring white light polarization profiles. This discovery provides a highly cost-effective technique for the generation of broadband orbital angular momentum and radially polarized beams.

Enhancement of the CAVE computer code. [aerodynamic heating package for nose cones and scramjet engine sidewalls

NASA Technical Reports Server (NTRS)

Rathjen, K. A.; Burk, H. O.

1983-01-01

The computer code CAVE (Conduction Analysis via Eigenvalues) is a convenient and efficient computer code for predicting two dimensional temperature histories within thermal protection systems for hypersonic vehicles. The capabilities of CAVE were enhanced by incorporation of the following features into the code: real gas effects in the aerodynamic heating predictions, geometry and aerodynamic heating package for analyses of cone shaped bodies, input option to change from laminar to turbulent heating predictions on leading edges, modification to account for reduction in adiabatic wall temperature with increase in leading sweep, geometry package for two dimensional scramjet engine sidewall, with an option for heat transfer to external and internal surfaces, print out modification to provide tables of select temperatures for plotting and storage, and modifications to the radiation calculation procedure to eliminate temperature oscillations induced by high heating rates. These new features are described.

Particle-in-cell simulations of asymmetric guide-field reconnection: quadrupolar structure of Hall magnetic field

NASA Astrophysics Data System (ADS)

Schmitz, R. G.; Alves, M. V.; Barbosa, M. V. G.

2017-12-01

One of the most important processes that occurs in Earth's magnetosphere is known as magnetic reconnection (MR). This process can be symmetric or asymmetric, depending basically on the plasma density and magnetic field in both sides of the current sheet. A good example of symmetric reconnection in terrestrial magnetosphere occurs in the magnetotail, where these quantities are similar on the north and south lobes. In the dayside magnetopause MR is asymmetric, since the plasma regimes and magnetic fields of magnetosheath and magnetosphere are quite different. Symmetric reconnection has some unique signatures. For example, the formation of a quadrupolar structure of Hall magnetic field and a bipolar Hall electric field that points to the center of the current sheet. The different particle motions in the presence of asymmetries change these signatures, causing the quadrupolar pattern to be distorted and forming a bipolar structure. Also, the bipolar Hall electric field is modified and gives rise to a single peak pointing toward the magnetosheat, considering an example of magnetopause reconnection. The presence of a guide-field can also distort the quadrupolar pattern, by giving a shear angle across the current sheet and altering the symmetric patterns, according to previous simulations and observations. Recently, a quadrupolar structure was observed in an asymmetric guide-field MR event using MMS (Magnetospheric Multiscale) mission data [Peng et al., JGR, 2017]. This event shows clearly that the density asymmetry and the guide-field were not sufficient to form signatures of asymmetric reconnection. Using the particle-in-cell code iPIC3D [Markidis et al, Mathematics and Computers in Simulation, 2010] with the MMS data from this event used to define input parameters, we found a quadrupolar structure of Hall magnetic field and a bipolar pattern of Hall electric field in ion scales, showing that our results are in an excellent agreement with the MMS observations. To our knowledge, this is the first time PIC simulations show this kind of results, since previous simulations have predicted bipolar pattern in the asymmetric guide-field reconnection.

Shift-Variant Multidimensional Systems.

DTIC Science & Technology

1985-05-29

i=0,1,** *N-1 in (3.1), one will get 0() i_0,1,* ,N-1 which is nonnegative due to the Perron - Frobenius Theorem [24]. That is, the A nonnegativity ...and the current input. The state-space model was extended in order to model 2-D discrete LSV systems with support on a causality cone . Subsequently...formulated as a special system of linear equations with nonnegative coefficients whose solution is required to satisfy con- straints like nonnegativity in

Determining the palaeodrainage of the Nile river from a provenance study of the Nile delta cone sediments: an on-going geochemical study

NASA Astrophysics Data System (ADS)

Fielding, Laura; Najman, Yani; Millar, Ian; Butterworth, Peter; Kneller, Ben; Garzanti, Eduardo

2013-04-01

This study documents the palaeodrainage history of the Nile River, in particular the time of transition from a small locally sourced drainage network to the initiation of an extensive Nile catchment, by conducting a provenance study of the well-dated Nile cone sediments. The identification of specific source inputs into the Nile cone has important implications for the prediction of reservoir quality and connectivity in hydrocarbon reservoirs. Presently, the Nile river drains as far south as south of Lake Victoria, with the White Nile draining largely Cratonic basement rocks of Archean to Proterozoic ages and the Blue Nile draining Cenozoic continental flood basalts and Neoproterozoic basement in Ethiopia. However, the timing of catchment expansion to its current extent is highly debated. There are a number of proposed palaeodrainage reconstructions, two of which are: A) The Blue Nile did not connect with the main (lower) Nile until the Late Messinian, and the White Nile did not connect with the lower Nile until at 0.5 Ma (e.g. Issawi and McCauley, 1992). In this model, the pre-Messinian Nile cone sediments are derived exclusively from the northern part of the present drainage basin, from the Red Sea Hills. B) The Blue Nile and Atbara Rivers have been connected to the main (lower) Nile since the Oligocene, simultaneous with large scale regional uplift and volcanism in the Ethiopian Highlands; with the river following a similar course to present day (Burke and Wells 1989). The palaeo-Nile cone sediments have the capacity to provide a unique archive of the river's highly debated palaeodrainage history. Our first objective was to characterise petrographically, geochemically and isotopically each possible source area (Ethiopian Flood Basalts, African Craton and Red Sea Hills) using a multidisciplinary approach in order to identify the presence (if any) of sediment from these sources in the delta core samples. Heavy mineral, petrographic, U-Pb zircon and rutile analyses so far support the hypothesis of the Blue Nile and/or the Red Sea Hills contributing detritus to the Nile delta since the Oligocene with very little input from the White Nile throughout the core. XRF, Sm-Nd and Rb-Sr analyses also point to a significant mafic (Blue Nile or Red Sea Hills) source since the Oligocene. More recent analytical work has involved studying the Lu/Hf of zircon. This is being carried out to assess the occurrence of the 30Ma zircons identified in the core, the Ethiopian Highlands and at Faiyum in the Western Desert. These results are preliminary, and the Red Sea Hills region in particular is subject to on-going work to more completely characterise its geochemical and isotopic signature.

Validation of Real-time Modeling of Coronal Mass Ejections Using the WSA-ENLIL+Cone Heliospheric Model

NASA Astrophysics Data System (ADS)

Romano, M.; Mays, M. L.; Taktakishvili, A.; MacNeice, P. J.; Zheng, Y.; Pulkkinen, A. A.; Kuznetsova, M. M.; Odstrcil, D.

2013-12-01

Modeling coronal mass ejections (CMEs) is of great interest to the space weather research and forecasting communities. We present recent validation work of real-time CME arrival time predictions at different satellites using the WSA-ENLIL+Cone three-dimensional MHD heliospheric model available at the Community Coordinated Modeling Center (CCMC) and performed by the Space Weather Research Center (SWRC). SWRC is an in-house research-based operations team at the CCMC which provides interplanetary space weather forecasting for NASA's robotic missions and performs real-time model validation. The quality of model operation is evaluated by comparing its output to a measurable parameter of interest such as the CME arrival time and geomagnetic storm strength. The Kp index is calculated from the relation given in Newell et al. (2007), using solar wind parameters predicted by the WSA-ENLIL+Cone model at Earth. The CME arrival time error is defined as the difference between the predicted arrival time and the observed in-situ CME shock arrival time at the ACE, STEREO A, or STEREO B spacecraft. This study includes all real-time WSA-ENLIL+Cone model simulations performed between June 2011-2013 (over 400 runs) at the CCMC/SWRC. We report hit, miss, false alarm, and correct rejection statistics for all three spacecraft. For hits we show the average absolute CME arrival time error, and the dependence of this error on CME input parameters such as speed, width, and direction. We also present the predicted geomagnetic storm strength (using the Kp index) error for Earth-directed CMEs.

Physical processes in directed ion beam sputtering. Ph.D. Thesis

NASA Technical Reports Server (NTRS)

Robinson, R. S.

1979-01-01

The general operation of a discharge chamber for the production of ions is described. A model is presented for the magnetic containment of both primary and secondary or Maxwellian electrons in the discharge plasma. Cross sections were calculated for energy and momentum transfer in binary collisions between like pairs of Ar, Kr, and Xe atoms in the energy range from about 1 eV to 1000 eV. These calculations were made from available pair interaction potentials using a classical model. Experimental data from the literature were fit to a theoretical expression for the Ar resonance charge exchange cross section over the same energy range. A model was developed that describes the processes of conical texturing of a surface due to simultaneous directed ion beam etching and sputter deposition of an impurity material. This model accurately predicts both a minimum temperature for texturing to take place and the variation of cone density with temperature. It also provides the correct order of magnitude of cone separation. It was predicted from the model, and subsequently verified experimentally, that a high sputter yield material could serve as a seed for coning of a lower sputter yield substrate. Seeding geometries and seed deposition rates were studied to obtain an important input to the theoretical texturing model.

Setups for in vitro assessment of RFID interference on pacemakers

NASA Astrophysics Data System (ADS)

Mattei, E.; Censi, F.; Delogu, A.; Ferrara, A.; Calcagnini, G.

2013-08-01

The aim of this study is to propose setups for in vitro assessment of RFID (radiofrequency identification) interference on pacemakers (PM). The voltage induced at the input stage of the PM by low-frequency (LF) and high-frequency (HF) RFID transmitters has been used to quantify the amount of the interference. A commercial PM was modified in order to measure the voltage at its input stage when exposed to a sinusoidal signal at 125 kHz and 13.56 MHz. At both frequencies, two antennas with different dimensions (diameter = 10 cm and 30 cm, respectively) were used to generate the interfering field, and the induced voltage was measured between the lead tip and the PM case (unipolar voltage), and between the tip and ring electrodes (bipolar voltage). The typical lead configurations adopted in similar studies or proposed by international standards, as well as lead paths closer to actual physiological implants were tested. At 125 kHz, the worst-case condition differs for the two antennas: the 10 cm antenna induced the highest voltage in the two-loop spiral configuration, whereas the 30 cm antenna in the 225 cm2 loop configuration. At 13.56 MHz, the highest voltage was observed for both the antennas in the 225 cm2 loop configuration. Bipolar voltages were found to be lower than the unipolar voltages induced in the same configurations, this difference being not as high as one could expect from theoretical considerations. The worst-case scenario, in terms of the induced voltage at the PM input stage, has been identified both for LF and HF readers, and for two sizes of transmitting antennas. These findings may provide the basis for the definition of a standard implant configuration and a lead path to test the EMI effects of LF and HF RFID transmitters on active implantable devices.

Restoration of visual function by expression of a light-gated mammalian ion channel in retinal ganglion cells or ON-bipolar cells

PubMed Central

Gaub, Benjamin M.; Berry, Michael H.; Holt, Amy E.; Reiner, Andreas; Kienzler, Michael A.; Dolgova, Natalia; Nikonov, Sergei; Aguirre, Gustavo D.; Beltran, William A.; Flannery, John G.; Isacoff, Ehud Y.

2014-01-01

Most inherited forms of blindness are caused by mutations that lead to photoreceptor cell death but spare second- and third-order retinal neurons. Expression of the light-gated excitatory mammalian ion channel light-gated ionotropic glutamate receptor (LiGluR) in retinal ganglion cells (RGCs) of the retina degeneration (rd1) mouse model of blindness was previously shown to restore some visual functions when stimulated by UV light. Here, we report restored retinal function in visible light in rodent and canine models of blindness through the use of a second-generation photoswitch for LiGluR, maleimide-azobenzene-glutamate 0 with peak efficiency at 460 nm (MAG0460). In the blind rd1 mouse, multielectrode array recordings of retinal explants revealed robust and uniform light-evoked firing when LiGluR-MAG0460 was targeted to RGCs and robust but diverse activity patterns in RGCs when LiGluR-MAG0460 was targeted to ON-bipolar cells (ON-BCs). LiGluR-MAG0460 in either RGCs or ON-BCs of the rd1 mouse reinstated innate light-avoidance behavior and enabled mice to distinguish between different temporal patterns of light in an associative learning task. In the rod-cone dystrophy dog model of blindness, LiGluR-MAG0460 in RGCs restored robust light responses to retinal explants and intravitreal delivery of LiGluR and MAG0460 was well tolerated in vivo. The results in both large and small animal models of photoreceptor degeneration provide a path to clinical translation. PMID:25489083

The expression analysis of Sfrs10 and Celf4 during mouse retinal development

PubMed Central

Karunakaran, Devi Krishna Priya; Congdon, Sean; Guerrette, Thomas; Banday, Abdul Rouf; Lemoine, Christopher; Chhaya, Nisarg; Kanadia, Rahul

2013-01-01

Processing of mRNAs including, alternative splicing (AS), mRNA transport and translation regulation are crucial to eukaryotic gene expression. For example, >90% of the gene in the human genome are known to undergo alternative splicing thereby expanding the proteome production capacity of a limited number of genes. Similarly, mRNA export and translation regulation plays a vital role in regulating protein production. Thus, it is important to understand how these RNA binding proteins including alternative splicing factors (ASFs) and mRNA transport and translation factors regulate these processes. Here we report the expression of an ASF, Serine-arginine rich splicing factor 10 (Sfrs10) and a mRNA translation regulation factor, CUGBP, elav like family member 4 (Celf4) in the developing mouse retina. Sfrs10 was expressed throughout postnatal (P) retinal development and was observed progressively in newly differentiating neurons. Immunofluorescence (IF) showed Sfrs10 in retinal ganglion cells (RGCs) at P0, followed by amacrine and bipolar cells, and at P8 it was enriched in red/green cone photoreceptor cells. By P22, Sfrs10 was observed in rod photoreceptors in a peri-nuclear pattern. Like Sfrs10, Celf4 was also observed in the developing retina, but with two distinct retinal isoforms. In situ hybridization (ISH) showed progressive expression of Celf4 in differentiating neurons, which was confirmed by IF that showed a dynamic shift in Celf4 localization. Early in development Celf4 expression was restricted to the nuclei of newly differentiating RGCs and later (E16 onwards) it was observed in the initial segments of RGC axons. Later, during postnatal development, Celf4 was observed in amacrine and bipolar cells, but here it was predominantly cytoplasmic and enriched in the two synaptic layers. Specifically, at P14, Celf4 was observed in the synaptic boutons of rod bipolar cells marked by Pkc-α. Thus, Celf4 might be regulating AS early in development besides its known role of regulating mRNA localization/translation. In all, our data suggests an important role for AS and mRNA localization/translation in retinal neuron differentiation. PMID:23932931

Acute destruction of the synaptic ribbon reveals a role for the ribbon in vesicle priming.

PubMed

Snellman, Josefin; Mehta, Bhupesh; Babai, Norbert; Bartoletti, Theodore M; Akmentin, Wendy; Francis, Adam; Matthews, Gary; Thoreson, Wallace; Zenisek, David

2011-07-24

In vision, balance and hearing, sensory receptor cells translate sensory stimuli into electrical signals whose amplitude is graded with stimulus intensity. The output synapses of these sensory neurons must provide fast signaling to follow rapidly changing stimuli while also transmitting graded information covering a wide range of stimulus intensity and must be able to sustain this signaling for long time periods. To meet these demands, specialized machinery for transmitter release, the synaptic ribbon, has evolved at the synaptic outputs of these neurons. We found that acute disruption of synaptic ribbons by photodamage to the ribbon markedly reduced both sustained and transient components of neurotransmitter release in mouse bipolar cells and salamander cones without affecting the ultrastructure of the ribbon or its ability to localize synaptic vesicles to the active zone. Our results indicate that ribbons mediate both slow and fast signaling at sensory synapses and support an additional role for the synaptic ribbon in priming vesicles for exocytosis at active zones.

Genome-wide association meta-analysis highlights light-induced signaling as a driver for refractive error.

PubMed

Tedja, Milly S; Wojciechowski, Robert; Hysi, Pirro G; Eriksson, Nicholas; Furlotte, Nicholas A; Verhoeven, Virginie J M; Iglesias, Adriana I; Meester-Smoor, Magda A; Tompson, Stuart W; Fan, Qiao; Khawaja, Anthony P; Cheng, Ching-Yu; Höhn, René; Yamashiro, Kenji; Wenocur, Adam; Grazal, Clare; Haller, Toomas; Metspalu, Andres; Wedenoja, Juho; Jonas, Jost B; Wang, Ya Xing; Xie, Jing; Mitchell, Paul; Foster, Paul J; Klein, Barbara E K; Klein, Ronald; Paterson, Andrew D; Hosseini, S Mohsen; Shah, Rupal L; Williams, Cathy; Teo, Yik Ying; Tham, Yih Chung; Gupta, Preeti; Zhao, Wanting; Shi, Yuan; Saw, Woei-Yuh; Tai, E-Shyong; Sim, Xue Ling; Huffman, Jennifer E; Polašek, Ozren; Hayward, Caroline; Bencic, Goran; Rudan, Igor; Wilson, James F; Joshi, Peter K; Tsujikawa, Akitaka; Matsuda, Fumihiko; Whisenhunt, Kristina N; Zeller, Tanja; van der Spek, Peter J; Haak, Roxanna; Meijers-Heijboer, Hanne; van Leeuwen, Elisabeth M; Iyengar, Sudha K; Lass, Jonathan H; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, André G; Vingerling, Johannes R; Lehtimäki, Terho; Raitakari, Olli T; Biino, Ginevra; Concas, Maria Pina; Schwantes-An, Tae-Hwi; Igo, Robert P; Cuellar-Partida, Gabriel; Martin, Nicholas G; Craig, Jamie E; Gharahkhani, Puya; Williams, Katie M; Nag, Abhishek; Rahi, Jugnoo S; Cumberland, Phillippa M; Delcourt, Cécile; Bellenguez, Céline; Ried, Janina S; Bergen, Arthur A; Meitinger, Thomas; Gieger, Christian; Wong, Tien Yin; Hewitt, Alex W; Mackey, David A; Simpson, Claire L; Pfeiffer, Norbert; Pärssinen, Olavi; Baird, Paul N; Vitart, Veronique; Amin, Najaf; van Duijn, Cornelia M; Bailey-Wilson, Joan E; Young, Terri L; Saw, Seang-Mei; Stambolian, Dwight; MacGregor, Stuart; Guggenheim, Jeremy A; Tung, Joyce Y; Hammond, Christopher J; Klaver, Caroline C W

2018-06-01

Refractive errors, including myopia, are the most frequent eye disorders worldwide and an increasingly common cause of blindness. This genome-wide association meta-analysis in 160,420 participants and replication in 95,505 participants increased the number of established independent signals from 37 to 161 and showed high genetic correlation between Europeans and Asians (>0.78). Expression experiments and comprehensive in silico analyses identified retinal cell physiology and light processing as prominent mechanisms, and also identified functional contributions to refractive-error development in all cell types of the neurosensory retina, retinal pigment epithelium, vascular endothelium and extracellular matrix. Newly identified genes implicate novel mechanisms such as rod-and-cone bipolar synaptic neurotransmission, anterior-segment morphology and angiogenesis. Thirty-one loci resided in or near regions transcribing small RNAs, thus suggesting a role for post-transcriptional regulation. Our results support the notion that refractive errors are caused by a light-dependent retina-to-sclera signaling cascade and delineate potential pathobiological molecular drivers.

Roller-gear drives for robotic manipulators design, fabrication and test

NASA Technical Reports Server (NTRS)

Anderson, William J.; Shipitalo, William

1991-01-01

Two single axis planetary roller-gear drives and a two axis roller-gear drive with dual inputs were designed for use as robotic transmissions. Each of the single axis drives is a two planet row, four planet arrangement with spur gears and compressively loaded cylindrical rollers acting in parallel. The two axis drive employs bevel gears and cone rollers acting in parallel. The rollers serve a dual function: they remove backlash from the system, and they transmit torque when the gears are not fully engaged.

The effects of Poynting-Robertson drag on solar sails

NASA Astrophysics Data System (ADS)

Abd El-Salam, F. A.

2018-06-01

In the present work, the concept of solar sailing and its developing spacecraft are presented. The effects of Poynting-Robertson drag on solar sails are considered. Some analytical control laws with some mentioned input constraints for optimizing solar sails dynamics in heliocentric orbit using Lagrange's planetary equations are obtained. Optimum force vector in a required direction is maximized by deriving optimal sail cone angle. New control laws that maximize thrust to obtain certain required maximization in some particular orbital element are obtained.

A supersonic three-dimensional code for flow over blunt bodies: Program documentation and test cases

NASA Technical Reports Server (NTRS)

Chaussee, D. S.; Mcmillan, O. J.

1980-01-01

The use of a computer code for the calculation of steady, supersonic, three dimensional, inviscid flow over blunt bodies is illustrated. Input and output are given and explained for two cases: a pointed code of 20 deg half angle at 15 deg angle of attack in a free stream with M sub infinite = 7, and a cone-ogive-cylinder at 10 deg angle of attack with M sub infinite = 2.86. A source listing of the computer code is provided.

A Resettable Keypad Lock with Visible Readout Based on Closed Bipolar Electrochemistry and Electrochromic Poly(3-methylthiophene) Films.

PubMed

Wang, Lei; Lian, Wenjing; Liu, Hongyun

2016-03-24

A closed bipolar electrode (BPE) system was developed with electrochromic poly(3-methylthiophene) (PMT) films electropolymerized on the ITO/rGO electrode as one pole of BPE in the reporting reservoir and the bare ITO electrode as another pole of BPE in the analyte reservoir, in which rGO represents reduced graphene oxide. Under a suitable driving voltage (Vtot), the electrochemical reduction/oxidation of electroactive probes, such as H2O2/glutathione (Glu), in the analyte reservoir could induce the reversible color change of PMT films in the reporting reservoir between blue and red. Based on this, a keypad lock with H2O2 , Glu, and Vtot =-3.0 V as the three inputs and the color change of PMT films as the visible output was established. This system was easily operated and did not need to synthesize the complex compounds or DNA molecules. The security system was easy to reset and could be used repeatedly. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Coordinated dynamic encoding in the retina using opposing forms of plasticity

PubMed Central

Kastner, David B.; Baccus, Stephen A.

2011-01-01

The range of natural inputs encoded by a neuron often exceeds its dynamic range. To overcome this limitation, neural populations divide their inputs among different cell classes, as with rod and cone photoreceptors, and adapt by shifting their dynamic range. We report that the dynamic behavior of retinal ganglion cells in salamanders, mice, and rabbits is divided into two opposing forms of short-term plasticity in different cell classes. One population of cells exhibited sensitization—a persistent elevated sensitivity following a strong stimulus. This novel dynamic behavior compensates for the information loss caused by the known process of adaptation occurring in a separate cell population. The two populations divide the dynamic range of inputs, with sensitizing cells encoding weak signals, and adapting cells encoding strong signals. In the two populations, the linear, threshold and adaptive properties are linked to preserve responsiveness when stimulus statistics change, with one population maintaining the ability to respond when the other fails. PMID:21909086

Rai1 frees mice from the repression of active wake behaviors by light.

PubMed

Diessler, Shanaz; Kostic, Corinne; Arsenijevic, Yvan; Kawasaki, Aki; Franken, Paul

2017-05-26

Besides its role in vision, light impacts physiology and behavior through circadian and direct ( aka 'masking') mechanisms. In Smith-Magenis syndrome (SMS), the dysregulation of both sleep-wake behavior and melatonin production strongly suggests impaired non-visual light perception. We discovered that mice haploinsufficient for the SMS causal gene, Retinoic acid induced-1 ( Rai1 ), were hypersensitive to light such that light eliminated alert and active-wake behaviors, while leaving time-spent-awake unaffected. Moreover, variables pertaining to circadian rhythm entrainment were activated more strongly by light. At the input level, the activation of rod/cone and suprachiasmatic nuclei (SCN) by light was paradoxically greatly reduced, while the downstream activation of the ventral-subparaventricular zone (vSPVZ) was increased. The vSPVZ integrates retinal and SCN input and, when activated, suppresses locomotor activity, consistent with the behavioral hypersensitivity to light we observed. Our results implicate Rai1 as a novel and central player in processing non-visual light information, from input to behavioral output.

Multi-phase Nature of a Radiation-driven Fountain with Nuclear Starburst in a Low-mass Active Galactic Nucleus

NASA Astrophysics Data System (ADS)

Wada, Keiichi; Schartmann, Marc; Meijerink, Rowin

2016-09-01

The structures and dynamics of molecular, atomic, and ionized gases are studied around a low-luminosity active galactic nucleus (AGN) with a small (2× {10}6{M}⊙ ) black hole using three-dimensional (3D) radiation-hydrodynamic simulations. We studied, for the first time, the non-equilibrium chemistry for the X-ray-dominated region in the “radiation-driven fountain” with supernova feedback. A double hollow cone structure is naturally formed without postulating a thick “torus” around a central source. The cone is occupied with an inhomogeneous, diffuse ionized gas and surrounded by a geometrically thick (h/r≳ 1) atomic gas. Dense molecular gases are distributed near the equatorial plane, and energy feedback from supernovae enhances their scale height. Molecular hydrogen exists in a hot phase (>1000 K) as well as in a cold (\\lt 100 {{K}}), dense (\\gt {10}3 {{cm}}-3) phase. The velocity dispersion of H2 in the vertical direction is comparable to the rotational velocity, which is consistent with near-infrared observations of nearby Seyfert galaxies. Using 3D radiation transfer calculations for the dust emission, we find polar emission in the mid-infrared band (12 μm), which is associated with bipolar outflows, as suggested in recent interferometric observations of nearby AGNs. If the viewing angle for the nucleus is larger than 75°, the spectral energy distribution is consistent with that of the Circinus galaxy. The multi-phase interstellar medium observed in optical/infrared and X-ray observations is also discussed.

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

PubMed Central

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

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

PubMed

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.

The influences of metabotropic receptor activation on cellular signaling and synaptic function in amacrine cells.

PubMed

Gleason, Evanna

2012-01-01

Amacrine cells receive glutamatergic input from bipolar cells and GABAergic, glycinergic, cholinergic, and dopaminergic input from other amacrine cells. Glutamate, GABA, glycine, and acetylcholine (ACh) interact with ionotropic receptors and it is these interactions that form much of the functional circuitry in the inner retina. However, glutamate, GABA, ACh, and dopamine also activate metabotropic receptors linked to second messenger pathways that have the potential to modify the function of individual cells as well as retinal circuitry. Here, the physiological effects of activating dopamine receptors, metabotropic glutamate receptors, GABAB receptors, and muscarinic ACh receptors on amacrine cells will be discussed. The retina also expresses metabotropic receptors and the biochemical machinery associated with the synthesis and degradation of endocannabinoids and sphingosine-1-phosphate (S1P). The effects of activating cannabinoid receptors and S1P receptors on amacrine cell function will also be addressed. Copyright © Cambridge University Press, 2012

High-Tc Superconducting Bolometer Noise Measurement Using Low Noise Transformers - Theory and Optimization

NASA Technical Reports Server (NTRS)

Aslam, Shahid; Jones, Hollis H.

2011-01-01

Care must always be taken when performing noise measurements on high-Tc superconducting materials to ensure that the results are not from the measurement system itself. One situation likely to occur is with low noise transformers. One of the least understood devices, it provides voltage gain for low impedance inputs (< 100 ), e.g., YBaCuO and GdBaCuO thin films, with comparatively lower noise levels than other devices for instance field effect and bipolar junction transistors. An essential point made in this paper is that because of the complex relationships between the transformer ports, input impedance variance alters the transformer s transfer function in particular, the low frequency cutoff shift. The transfer of external and intrinsic transformer noise to the output along with optimization and precautions are treated; all the while, we will cohesively connect the transfer function shift, the load impedance, and the actual noise at the transformer output.

Real-time Ensemble Forecasting of Coronal Mass Ejections using the WSA-ENLIL+Cone Model

NASA Astrophysics Data System (ADS)

Mays, M. L.; Taktakishvili, A.; Pulkkinen, A. A.; MacNeice, P. J.; Rastaetter, L.; Kuznetsova, M. M.; Odstrcil, D.

2013-12-01

Ensemble forecasting of coronal mass ejections (CMEs) provides significant information in that it provides an estimation of the spread or uncertainty in CME arrival time predictions due to uncertainties in determining CME input parameters. Ensemble modeling of CME propagation in the heliosphere is performed by forecasters at the Space Weather Research Center (SWRC) using the WSA-ENLIL cone model available at the Community Coordinated Modeling Center (CCMC). SWRC is an in-house research-based operations team at the CCMC which provides interplanetary space weather forecasting for NASA's robotic missions and performs real-time model validation. A distribution of n (routinely n=48) CME input parameters are generated using the CCMC Stereo CME Analysis Tool (StereoCAT) which employs geometrical triangulation techniques. These input parameters are used to perform n different simulations yielding an ensemble of solar wind parameters at various locations of interest (satellites or planets), including a probability distribution of CME shock arrival times (for hits), and geomagnetic storm strength (for Earth-directed hits). Ensemble simulations have been performed experimentally in real-time at the CCMC since January 2013. We present the results of ensemble simulations for a total of 15 CME events, 10 of which were performed in real-time. The observed CME arrival was within the range of ensemble arrival time predictions for 5 out of the 12 ensemble runs containing hits. The average arrival time prediction was computed for each of the twelve ensembles predicting hits and using the actual arrival time an average absolute error of 8.20 hours was found for all twelve ensembles, which is comparable to current forecasting errors. Some considerations for the accuracy of ensemble CME arrival time predictions include the importance of the initial distribution of CME input parameters, particularly the mean and spread. When the observed arrivals are not within the predicted range, this still allows the ruling out of prediction errors caused by tested CME input parameters. Prediction errors can also arise from ambient model parameters such as the accuracy of the solar wind background, and other limitations. Additionally the ensemble modeling setup was used to complete a parametric event case study of the sensitivity of the CME arrival time prediction to free parameters for ambient solar wind model and CME.

Dynamical Adaptation in Photoreceptors

PubMed Central

Clark, Damon A.; Benichou, Raphael; Meister, Markus; Azeredo da Silveira, Rava

2013-01-01

Adaptation is at the heart of sensation and nowhere is it more salient than in early visual processing. Light adaptation in photoreceptors is doubly dynamical: it depends upon the temporal structure of the input and it affects the temporal structure of the response. We introduce a non-linear dynamical adaptation model of photoreceptors. It is simple enough that it can be solved exactly and simulated with ease; analytical and numerical approaches combined provide both intuition on the behavior of dynamical adaptation and quantitative results to be compared with data. Yet the model is rich enough to capture intricate phenomenology. First, we show that it reproduces the known phenomenology of light response and short-term adaptation. Second, we present new recordings and demonstrate that the model reproduces cone response with great precision. Third, we derive a number of predictions on the response of photoreceptors to sophisticated stimuli such as periodic inputs, various forms of flickering inputs, and natural inputs. In particular, we demonstrate that photoreceptors undergo rapid adaptation of response gain and time scale, over ∼ 300 ms—i. e., over the time scale of the response itself—and we confirm this prediction with data. For natural inputs, this fast adaptation can modulate the response gain more than tenfold and is hence physiologically relevant. PMID:24244119

Methods of high current magnetic field generator for transcranial magnetic stimulation application

NASA Astrophysics Data System (ADS)

Bouda, N. R.; Pritchard, J.; Weber, R. J.; Mina, M.

2015-05-01

This paper describes the design procedures and underlying concepts of a novel High Current Magnetic Field Generator (HCMFG) with adjustable pulse width for transcranial magnetic stimulation applications. This is achieved by utilizing two different switching devices, the MOSFET and insulated gate bipolar transistor (IGBT). Results indicate that currents as high as ±1200 A can be generated with inputs of +/-20 V. Special attention to tradeoffs between field generators utilizing IGBT circuits (HCMFG1) and MOSFET circuits (HCMFG2) was considered. The theory of operation, design, experimental results, and electronic setup are presented and analyzed.

Methods of high current magnetic field generator for transcranial magnetic stimulation application

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

Bouda, N. R., E-mail: nybouda@iastate.edu; Pritchard, J.; Weber, R. J.

This paper describes the design procedures and underlying concepts of a novel High Current Magnetic Field Generator (HCMFG) with adjustable pulse width for transcranial magnetic stimulation applications. This is achieved by utilizing two different switching devices, the MOSFET and insulated gate bipolar transistor (IGBT). Results indicate that currents as high as ±1200 A can be generated with inputs of +/−20 V. Special attention to tradeoffs between field generators utilizing IGBT circuits (HCMFG{sub 1}) and MOSFET circuits (HCMFG{sub 2}) was considered. The theory of operation, design, experimental results, and electronic setup are presented and analyzed.

Colour vision in ADHD: part 1--testing the retinal dopaminergic hypothesis.

PubMed

Kim, Soyeon; Al-Haj, Mohamed; Chen, Samantha; Fuller, Stuart; Jain, Umesh; Carrasco, Marisa; Tannock, Rosemary

2014-10-24

To test the retinal dopaminergic hypothesis, which posits deficient blue color perception in ADHD, resulting from hypofunctioning CNS and retinal dopamine, to which blue cones are exquisitely sensitive. Also, purported sex differences in red color perception were explored. 30 young adults diagnosed with ADHD and 30 healthy young adults, matched on age and gender, performed a psychophysical task to measure blue and red color saturation and contrast discrimination ability. Visual function measures, such as the Visual Activities Questionnaire (VAQ) and Farnsworth-Munsell 100 hue test (FMT), were also administered. Females with ADHD were less accurate in discriminating blue and red color saturation relative to controls but did not differ in contrast sensitivity. Female control participants were better at discriminating red saturation than males, but no sex difference was present within the ADHD group. Poorer discrimination of red as well as blue color saturation in the female ADHD group may be partly attributable to a hypo-dopaminergic state in the retina, given that color perception (blue-yellow and red-green) is based on input from S-cones (short wavelength cone system) early in the visual pathway. The origin of female superiority in red perception may be rooted in sex-specific functional specialization in hunter-gather societies. The absence of this sexual dimorphism for red colour perception in ADHD females warrants further investigation.

Bipolar Disorder in Nursing Homes: Impact on Antipsychotic Use, Diagnosis Patterns, and New Diagnoses in People with Dementia.

PubMed

Carnahan, Ryan M; Letuchy, Elena M

2018-01-01

Nursing home quality measures include the proportion of residents who receive antipsychotics. Residents with bipolar disorder are included even though antipsychotics are FDA-approved for this indication. We evaluated how including residents with bipolar disorder impacted the antipsychotic use quality measure for long-stay residents. We evaluated the agreement of minimum data set (MDS) bipolar disorder diagnoses with Medicare data, whether dementia was diagnosed before bipolar disorder, and how less-specific bipolar disorder diagnoses impacted findings. Cross-sectional study. Nursing homes in Iowa. 21,955 long-stay nursing home residents in the first quarter of 2014. We identified antipsychotic use and bipolar disorder using MDS data. We compared MDS bipolar disorder diagnoses with Chronic Conditions Warehouse (CCW) "ever" bipolar disorder indicators, and prior year claims. We compared CCW condition onset dates to identify bipolar disorder diagnosed after dementia. The mean (SD) proportion receiving antipsychotics was 19.6% (11.1%) with bipolar disorder and 18.3% (10.8%) without. The positive predictive value (PPV) of MDS bipolar disorder diagnoses was 80.2% versus CCW lifetime indicators, and 74.6% versus claims. PPV decreased by 27.1% when "bipolar disorder, unspecified" and "other bipolar disorders" diagnoses were excluded. Nearly three-quarters of residents with bipolar disorder had dementia. Over half of those with dementia had dementia first per CCW records. This proportion was lower among those with more specific bipolar disorder diagnoses or MDS bipolar disorder indicators. Bipolar disorder in nursing home residents is often first diagnosed after dementia using nonspecific diagnoses. This practice deserves further evaluation. Copyright © 2017 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

A resettable and reprogrammable keypad lock based on electrochromic Prussian blue films and biocatalysis of immobilized glucose oxidase in a bipolar electrode system.

PubMed

Yu, Xue; Liang, Jiying; Yang, Tiangang; Gong, Mengjie; Xi, Dongman; Liu, Hongyun

2018-01-15

Herein, a resettable and reprogrammable biomolecular keypad lock on the basis of a closed bipolar electrode (BPE) system was established. In this system, one ITO electrode with immobilized chitosan (CS) and glucose oxidase (GOD), designated as CS-GOD, acted as one pole of BPE in the sensing cell; another ITO with electrodeposited Prussian blue (PB) films as the other pole in the reporting cell. The addition of ascorbic acid (AA) in the sensing cell with driving voltage (V tot ) at +2.5V would make the PB films become Prussian white (PW) in the reporting cell, accompanied by the color change from blue to nearly transparent. On the other hand, with the help of oxygen, the addition of glucose in the sensing cell with V tot at -1.5V would induce PW back to PB. The change of color and the corresponding UV-vis absorbance at 700nm for the PB/PW films in the reporting cell could be reversibly switched by changing the solute in the sensing cell between AA and glucose and then switching V tot between +2.5 and -1.5V. Based on these, a keypad lock was developed with AA, glucose and V tot as 3 inputs, and the color change of the PB/PW films as the output. This keypad lock system combined enzymatic catalysis with bipolar electrochemistry, demonstrating some unique advantages such as good reprogrammability, easy resettability and visual readout by naked eye. Copyright © 2017 Elsevier B.V. All rights reserved.

Systemic challenges in bipolar disorder management: A patient-centered approach.

PubMed

Nestsiarovich, Anastasiya; Hurwitz, Nathaniel G; Nelson, Stuart J; Crisanti, Annette S; Kerner, Berit; Kuntz, Matt J; Smith, Alicia N; Volesky, Emma; Schroeter, Quentin L; DeShaw, Jason L; Young, S Stanley; Obenchain, Robert L; Krall, Ronald L; Jordan, Kimmie; Fawcett, Jan; Tohen, Mauricio; Perkins, Douglas J; Lambert, Christophe G

2017-12-01

As part of a series of Patient-Centered Outcomes Research Institute-funded large-scale retrospective observational studies on bipolar disorder (BD) treatments and outcomes, we sought the input of patients with BD and their family members to develop research questions. We aimed to identify systemic root causes of patient-reported challenges with BD management in order to guide subsequent studies and initiatives. Three focus groups were conducted where patients and their family members (total n = 34) formulated questions around the central theme, "What do you wish you had known in advance or over the course of treatment for BD?" In an affinity mapping exercise, participants clustered their questions and ranked the resulting categories by importance. The research team and members of our patient partner advisory council further rated the questions by expected impact on patients. Using a Theory of Constraints systems thinking approach, several causal models of BD management challenges and their potential solution were developed with patients using the focus group data. A total of 369 research questions were mapped to 33 categories revealing 10 broad themes. The top priorities for patient stakeholders involved pharmacotherapy and treatment alternatives. Analysis of causal relationships underlying 47 patient concerns revealed two core conflicts: for patients, whether or not to take pharmacotherapy, and for mental health services, the dilemma of care quality vs quantity. To alleviate the core conflicts identified, BD management requires a coordinated multidisciplinary approach including: improved access to mental health services, objective diagnostics, sufficient provider visit time, evidence-based individualized treatment, and psychosocial support. © 2017 The Authors. Bipolar Disorders Published by John Wiley & Sons Ltd.

Comparison of the ontogeny of the vesicular glutamate transporter 3 (VGLUT3) with VGLUT1 and VGLUT2 in the rat retina.

PubMed

Stella, Salvatore L; Li, Stefanie; Sabatini, Andrea; Vila, Alejandro; Brecha, Nicholas C

2008-06-18

Glutamate is the major excitatory neurotransmitter in the retina, and most glutamatergic neurons express one of the three known vesicular glutamate transporters (VGLUT1, 2, or 3). However, the expression profiles of these transporters vary greatly in the retina. VGLUT1 is expressed by photoreceptor and bipolar cell terminals, and VGLUT2 appears to be predominately expressed by ganglion cells, and perhaps Müller cells, cone photoreceptor terminals, and horizontal cells in some species. The discovery of a third vesicular glutamate transporter, VGLUT3, has brought about speculation concerning its role and function based on its expression in amacrine cells. To address this we studied the postnatal development of VGLUT3 from day 0 through adult in the rat retina, and compared this with the expression patterns of VGLUT1 and VGLUT2. VGLUT3 expression was restricted to a population of amacrine cells. Expression of VGLUT3 was first observed at postnatal day 10 (P10) in the soma and some processes, which extensively arborized in both the ON and OFF sublamina of the IPL by P15. In contrast, VGLUT1 and VGLUT2 expression appeared earlier than VGLUT3; with VGLUT1 initially detected at P5 in photoreceptor terminals and P6 in bipolar terminals, and VGLUT2 immunoreactivity initially detected at P0 in ganglion cell bodies, and remained prominent throughout all stages of development. Interestingly, VGLUT3 has extensive somatic expression throughout development, which could be involved in non-synaptic modulation by glutamate in developing retina, and could influence trophic and extra-synaptic neuronal signaling by glutamate in the inner retina.

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

PubMed

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.

SU-E-T-252: Developing a Pencil Beam Dose Calculation Algorithm for CyberKnife System

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

Liang, B; Duke University Medical Center, Durham, NC; Liu, B

2015-06-15

Purpose: Currently there are two dose calculation algorithms available in the Cyberknife planning system: ray-tracing and Monte Carlo, which is either not accurate or time-consuming for irregular field shaped by the MLC that was recently introduced. The purpose of this study is to develop a fast and accurate pencil beam dose calculation algorithm which can handle irregular field. Methods: A pencil beam dose calculation algorithm widely used in Linac system is modified. The algorithm models both primary (short range) and scatter (long range) components with a single input parameter: TPR{sub 20}/{sub 10}. The TPR{sub 20}/{sub 20}/{sub 10} value was firstmore » estimated to derive an initial set of pencil beam model parameters (PBMP). The agreement between predicted and measured TPRs for all cones were evaluated using the root mean square of the difference (RMSTPR), which was then minimized by adjusting PBMPs. PBMPs are further tuned to minimize OCR RMS (RMSocr) by focusing at the outfield region. Finally, an arbitrary intensity profile is optimized by minimizing RMSocr difference at infield region. To test model validity, the PBMPs were obtained by fitting to only a subset of cones (4) and applied to all cones (12) for evaluation. Results: With RMS values normalized to the dmax and all cones combined, the average RMSTPR at build-up and descending region is 2.3% and 0.4%, respectively. The RMSocr at infield, penumbra and outfield region is 1.5%, 7.8% and 0.6%, respectively. Average DTA in penumbra region is 0.5mm. There is no trend found in TPR or OCR agreement among cones or depths. Conclusion: We have developed a pencil beam algorithm for Cyberknife system. The prediction agrees well with commissioning data. Only a subset of measurements is needed to derive the model. Further improvements are needed for TPR buildup region and OCR penumbra. Experimental validations on MLC shaped irregular field needs to be performed. This work was partially supported by the National Natural Science Foundation of China (61171005) and the China Scholarship Council (CSC)« less

Alert Response to Motion Onset in the Retina

PubMed Central

Chen, Eric Y.; Marre, Olivier; Fisher, Clark; Schwartz, Greg; Levy, Joshua; da Silveira, Rava Azeredo

2013-01-01

Previous studies have shown that motion onset is very effective at capturing attention and is more salient than smooth motion. Here, we find that this salience ranking is present already in the firing rate of retinal ganglion cells. By stimulating the retina with a bar that appears, stays still, and then starts moving, we demonstrate that a subset of salamander retinal ganglion cells, fast OFF cells, responds significantly more strongly to motion onset than to smooth motion. We refer to this phenomenon as an alert response to motion onset. We develop a computational model that predicts the time-varying firing rate of ganglion cells responding to the appearance, onset, and smooth motion of a bar. This model, termed the adaptive cascade model, consists of a ganglion cell that receives input from a layer of bipolar cells, represented by individual rectified subunits. Additionally, both the bipolar and ganglion cells have separate contrast gain control mechanisms. This model captured the responses to our different motion stimuli over a wide range of contrasts, speeds, and locations. The alert response to motion onset, together with its computational model, introduces a new mechanism of sophisticated motion processing that occurs early in the visual system. PMID:23283327

Optical correlation based pose estimation using bipolar phase grayscale amplitude spatial light modulators

NASA Astrophysics Data System (ADS)

Outerbridge, Gregory John, II

Pose estimation techniques have been developed on both optical and digital correlator platforms to aid in the autonomous rendezvous and docking of spacecraft. This research has focused on the optical architecture, which utilizes high-speed bipolar-phase grayscale-amplitude spatial light modulators as the image and correlation filter devices. The optical approach has the primary advantage of optical parallel processing: an extremely fast and efficient way of performing complex correlation calculations. However, the constraints imposed on optically implementable filters makes optical correlator based posed estimation technically incompatible with the popular weighted composite filter designs successfully used on the digital platform. This research employs a much simpler "bank of filters" approach to optical pose estimation that exploits the inherent efficiency of optical correlation devices. A novel logarithmically mapped optically implementable matched filter combined with a pose search algorithm resulted in sub-degree standard deviations in angular pose estimation error. These filters were extremely simple to generate, requiring no complicated training sets and resulted in excellent performance even in the presence of significant background noise. Common edge detection and scaling of the input image was the only image pre-processing necessary for accurate pose detection at all alignment distances of interest.

Comparative investigation of InGaP/GaAs/GaAsBi and InGaP/GaAs heterojunction bipolar transistors

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

Wu, Yi-Chen; Tsai, Jung-Hui, E-mail: jhtsai@nknucc.nknu.edu.tw; Chiang, Te-Kuang

2015-10-15

In this article the characteristics of In{sub 0.49}Ga{sub 0.51}P/GaAs/GaAs{sub 0.975}Bi{sub 0.025} and In{sub 0.49}Ga{sub 0.51}P/GaAs heterojunction bipolar transistor (HBTs) are demonstrated and compared by two-dimensional simulated analysis. As compared to the traditional InGaP/GaAs HBT, the studied InGaP/GaAs/GaAsBi HBT exhibits a higher collector current, a lower base-emitter (B–E) turn-on voltage, and a relatively lower collector-emitter offset voltage of only 7 mV. Because the more electrons stored in the base is further increased in the InGaP/GaAs/GaAsBi HBT, it introduces the collector current to increase and the B–E turn-on voltage to decrease for low input power applications. However, the current gain is slightlymore » smaller than the traditional InGaP/GaAs HBT attributed to the increase of base current for the minority carriers stored in the GaAsBi base.« less

Color- and motion-specific units in the tectum opticum of goldfish.

PubMed

Gruber, Morna; Behrend, Konstantin; Neumeyer, Christa

2016-01-05

Extracellular recordings were performed from 69 units at different depths between 50 and [Formula: see text]m below the surface of tectum opticum in goldfish. Using large field stimuli (86[Formula: see text] visual angle) of 21 colored HKS-papers we were able to record from 54 color-sensitive units. The colored papers were presented for 5[Formula: see text]s each. They were arranged in the sequence of the color circle in humans separated by gray of medium brightness. We found 22 units with best responses between orange, red and pink. About 12 of these red-sensitive units were of the opponent "red-ON/blue-green-OFF" type as found in retinal bipolar- and ganglion cells as well. Most of them were also activated or inhibited by black and/or white. Some units responded specifically to red either with activation or inhibition. 18 units were sensitive to blue and/or green, 10 of them to both colors and most of them to black as well. They were inhibited by red, and belonged to the opponent "blue-green-ON/red-OFF" type. Other units responded more selectively either to blue, to green or to purple. Two units were selectively sensitive to yellow. A total of 15 units were sensitive to motion, stimulated by an excentrically rotating black and white random dot pattern. Activity of these units was also large when a red-green random dot pattern of high L-cone contrast was used. Activity dropped to zero when the red-green pattern did not modulate the L-cones. Neither of these motion selective units responded to any color. The results directly show color-blindness of motion vision, and confirm the hypothesis of separate and parallel processing of "color" and "motion".

Parenteral Lipid Dose Restriction With Soy Oil, Not Fish Oil, Preserves Retinal Function in Neonatal Piglets.

PubMed

Lansing, Marihan; Sauvé, Yves; Dimopoulos, Ioannis; Field, Catherine J; Suh, Miyoung; Wizzard, Pamela; Goruk, Susan; Lim, David; Muto, Mitsuru; Wales, Paul; Turner, Justine

2018-03-13

A dietary supply of docosahexaenoic acid (DHA) and arachidonic acid (AA) is critical for neonatal retinal development. Both are absent/minimal in parenteral nutrition (PN) using soy-oil emulsions ([SO] Intralipid®) traditionally used for neonatal intestinal failure. In contrast, fish-oil emulsions ([FO] Omegaven®) are enriched in DHA/AA. The aim of this study was to compare retinal function and fatty acid content in neonatal piglets fed PN with SO or FO. Two-5-day-old piglets were randomly allocated to SO (n = 4) or FO (n = 4), provided at equivalent doses (5g/kg/d). After 14 days of PN, retinal function was assessed by electroretinography and retinas were harvested for fatty acid content analysis. Sow-fed piglets served as a reference (REF). Light flash-elicited stoppage of cone and rod dark-currents (a-waves) and the ensuing postsynaptic activation of cone and rod ON bipolar cells (b-waves) were comparable between SO and REF. Responses recorded from FO were subnormal (P <0.001) when compared with both SO and REF. Retinal DHA content was similar in both groups (FO, 14.59% vs SO, 12.22%; P = 0.32); while AA was lower in FO (FO, 6.01% vs SO, 8.21%; P = .001). Paradoxically, FO containing more DHA and AA did not preserve retinal function when compared with the same low dose of SO. This may be due to the reduced AA enrichment in the retina with FO treatment. Further investigation into the ideal amounts of DHA and AA for optimal neonatal retinal function is required. © 2018 American Society for Parenteral and Enteral Nutrition.

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

PubMed

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.

Enhanced neurocognitive functioning and positive temperament in twins discordant for bipolar disorder.

PubMed

Higier, Rachel G; Jimenez, Amy M; Hultman, Christina M; Borg, Jacqueline; Roman, Cristina; Kizling, Isabelle; Larsson, Henrik; Cannon, Tyrone D

2014-11-01

Based on evidence linking creativity and bipolar disorder, a model has been proposed whereby factors influencing liability to bipolar disorder confer certain traits with positive effects on reproductive fitness. The authors tested this model by examining key traits known to be associated with evolutionary fitness, namely, temperament and neurocognition, in individuals carrying liability for bipolar disorder. Schizophrenia probands and their co-twins were included as psychiatric controls. Twin pairs discordant for bipolar disorder and schizophrenia and control pairs were identified through the Swedish Twin Registry. The authors administered a neuropsychological test battery and temperament questionnaires to samples of bipolar probands, bipolar co-twins, schizophrenia probands, schizophrenia co-twins, and controls. Multivariate mixed-model analyses of variance were conducted to compare groups on temperament and neurocognitive scores. Bipolar co-twins showed elevated scores on a "positivity" temperament scale compared with controls and bipolar probands, while bipolar probands scored higher on a "negativity" scale compared with their co-twins and controls, who did not differ. Additionally, bipolar co-twins showed superior performance compared with controls on tests of verbal learning and fluency, while bipolar probands showed performance decrements across all neurocognitive domains. In contrast, schizophrenia co-twins showed attenuated impairments in positivity and overall neurocognitive functioning relative to their ill proband counterparts. These findings suggest that supra-normal levels of sociability and verbal functioning may be associated with liability for bipolar disorder. These effects were specific to liability for bipolar disorder and did not apply to schizophrenia. Such benefits may provide a partial explanation for the persistence of bipolar illness in the population.

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

ERIC Educational Resources Information Center

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…

Rai1 frees mice from the repression of active wake behaviors by light

PubMed Central

Diessler, Shanaz; Kostic, Corinne; Arsenijevic, Yvan; Kawasaki, Aki; Franken, Paul

2017-01-01

Besides its role in vision, light impacts physiology and behavior through circadian and direct (aka ‘masking’) mechanisms. In Smith-Magenis syndrome (SMS), the dysregulation of both sleep-wake behavior and melatonin production strongly suggests impaired non-visual light perception. We discovered that mice haploinsufficient for the SMS causal gene, Retinoic acid induced-1 (Rai1), were hypersensitive to light such that light eliminated alert and active-wake behaviors, while leaving time-spent-awake unaffected. Moreover, variables pertaining to circadian rhythm entrainment were activated more strongly by light. At the input level, the activation of rod/cone and suprachiasmatic nuclei (SCN) by light was paradoxically greatly reduced, while the downstream activation of the ventral-subparaventricular zone (vSPVZ) was increased. The vSPVZ integrates retinal and SCN input and, when activated, suppresses locomotor activity, consistent with the behavioral hypersensitivity to light we observed. Our results implicate Rai1 as a novel and central player in processing non-visual light information, from input to behavioral output. DOI: http://dx.doi.org/10.7554/eLife.23292.001 PMID:28548639

Clinical variables and implications of the personality on the outcome of bipolar illness: a pilot study

PubMed Central

Casas-Barquero, Nieves; García-López, Olga; Fernández-Argüelles, Pedro; Camacho-Laraña, Manuel

2007-01-01

Outcome in bipolar patients is affected by comorbidity. Comorbid personality disorders are frequent and may complicate the course of bipolar illness. This pilot study examined a series of 40 euthymic bipolar patients (DSM-IV criteria) (bipolar I disorder 31, bipolar II disorder 9) to assess the effect of clinical variables and the influence of comorbid personality on the clinical course of bipolar illness. Bipolar patients with a diagnosis of comorbid personality disorder (n = 30) were compared with “pure” bipolar patients (n = 10) with regard to demographic, clinical, and course of illness variables. Comorbid personality disorder was diagnosed in 75% of patients according to ICD-10 criteria, with obsessive-compulsive personality disorder being the most frequent type. Sixty-three per cent of subjects had more than one comorbid personality disorder. Bipolar patients with and without comorbid personality disorder showed no significant differences regarding features of the bipolar illness, although the group with comorbid personality disorder showed a younger age at onset, more depressive episodes, and longer duration of bipolar illness. In subjects with comorbid personality disorders, the number of hospitalizations correlated significantly with depressive episodes and there was an inverse correlation between age at the first episode and duration of bipolar illness. These findings, however, should be interpreted taking into account the preliminary nature of a pilot study and the contamination of the sample with too many bipolar II patients. PMID:19300559

Design Studies for a Far Infrared Absolute Spectrometer for the Cosmic Background Explorer

NASA Technical Reports Server (NTRS)

Johnson, N. J. E.

1980-01-01

Unrelenting symmetry of design is required to assure the thermal balance of a cryogenically cooled, rapid scan interferometer spectrometer to be mounted in vacuum with the Cosmic Background Explorer liquid helium dewar. The instrument receives inputs from Winston cone optical flux collectors, one open to space and a second coupled to a black body reference source. A differential instrument, the spectrometer produces outputs corresponding to the Fourier transform of the spectral radiance difference between the two inputs. The two outputs are sensed by four detectors, two optimized for shorter wavelength response, and two optimized for longer wavelengths. The optical design, detector and signal channel, system sensitivity, mechanics, thermal control and cryogenics, electronics and power systems, command and control, calibration, system test requirements, and the instrument interface are discussed. Recommendations for continued work are indicated for the superconducting reflective horns, the motor bearing and drive, and design detail.

The Retina of Asian and African Elephants: Comparison of Newborn and Adult.

PubMed

Kuhrt, Heidrun; Bringmann, Andreas; Härtig, Wolfgang; Wibbelt, Gudrun; Peichl, Leo; Reichenbach, Andreas

2017-01-01

Elephants are precocial mammals that are relatively mature as newborns and mobile shortly after birth. To determine whether the retina of newborn elephants is capable of supporting the mobility of elephant calves, we compared the retinal structures of 2 newborn elephants (1 African and 1 Asian) and 2 adult animals of both species by immunohistochemical and morphometric methods. For the first time, we present here a comprehensive qualitative and quantitative characterization of the cellular composition of the newborn and the adult retinas of 2 elephant species. We found that the retina of elephants is relatively mature at birth. All retinal layers were well discernible, and various retinal cell types were detected in the newborns, including Müller glial cells (expressing glutamine synthetase and cellular retinal binding protein; CRALBP), cone photoreceptors (expressing S-opsin or M/L-opsin), protein kinase Cα-expressing bipolar cells, tyrosine hydroxylase-, choline acetyltransferase (ChAT)-, calbindin-, and calretinin-expressing amacrine cells, and calbindin-expressing horizontal cells. The retina of newborn elephants contains discrete horizontal cells which coexpress ChAT, calbindin, and calretinin. While the overall structure of the retina is very similar between newborn and adult elephants, various parameters change after birth. The postnatal thickening of the retinal ganglion cell axons and the increase in ganglion cell soma size are explained by the increase in body size after birth, and the decreases in the densities of neuronal and glial cells are explained by the postnatal expansion of the retinal surface area. The expression of glutamine synthetase and CRALBP in the Müller cells of newborn elephants suggests that the cells are already capable of supporting the activities of photoreceptors and neurons. As a peculiarity, the elephant retina contains both normally located and displaced giant ganglion cells, with single cells reaching a diameter of more than 50 µm in adults and therefore being almost in the range of giant retinal ganglion cells found in aquatic mammals. Some of these ganglion cells are displaced into the inner nuclear layer, a unique feature of terrestrial mammals. For the first time, we describe here the occurrence of many bistratified rod bipolar cells in the elephant retina. These bistratified bipolar cells may improve nocturnal contrast perception in elephants given their arrhythmic lifestyle. © 2017 S. Karger AG, Basel.

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

PubMed

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.

Hypnotic susceptibility and affective states in bipolar I and II disorders.

PubMed

Zhang, Bingren; Wang, Jiawei; Zhu, Qisha; Ma, Guorong; Shen, Chanchan; Fan, Hongying; Wang, Wei

2017-11-09

Highly hypnotizable individuals have impaired executive function, elevated motor impulsivity and increased emotional sensitivity, which are sometimes found in bipolar disorder patients. It is then reasonable to assume that certain aspects of hypnotic susceptibility differ with the types of bipolar disorder. The Stanford Hypnotic Susceptibility Scale: Form C (SHSS:C) test, the Mood Disorder Questionnaire (MDQ), the Hypomanic Checklist-32 (HCL-32) and the Plutchick-van Praag Depression Inventory (PVP) were applied to 62 patients with bipolar I disorder, 33 bipolar II disorder, and 120 healthy volunteers. The passing rate of the SHSS:C 'Moving hands apart' item was higher in bipolar I patients than in controls, whereas for 'Mosquito hallucination' the rate was lower. Bipolar I and II patients scored significantly higher on MDQ, HCL-32 and PVP scales than controls. The passing rates of 'Mosquito hallucination' in controls, 'Arm rigidity' in bipolar I, and 'Age regression' in bipolar II predicted the respective MDQ scores. In contrast to cognitive suggestions, bipolar I patients followed motor suggestions more often under hypnosis. Furthermore, both bipolar disorder patients and healthy volunteers demonstrated associations between mania levels and certain hypnotic susceptibility features. Our study aids in better understanding the altered conscious states in bipolar disorders, and encourages the use of related psychotherapy for these patients.

Risk of sexual transmitted infection following bipolar disorder: a nationwide population-based cohort study.

PubMed

Lee, Shyh-Chyang; Hu, Chang-Kuo; Hung, Jeng-Hsiu; Yang, Albert C; Tsai, Shih-Jen; Huang, Min-Wei; Hu, Li-Yu; Shen, Cheng-Che

2018-04-03

Bipolar disorder is a severe mental disorder associated with functional and cognitive impairment. Numerous studies have investigated associations between sexually transmitted infections (STIs) and psychiatric illnesses. However, the results of these studies are controversial. We explored the association between bipolar disorder and the subsequent development of STIs, including human immunodeficiency virus infection; primary, secondary, and latent syphilis; genital warts; gonorrhea; chlamydial infection; and trichomoniasis. The bipolar cohort consisted of 1293 patients, and the comparison cohort consisted of 5172 matched control subjects without bipolar disorder. The incidence of subsequent STIs (hazard ratio (HR) = 2.23, 95% confidence interval (CI) 1.68-2.96) was higher among the patients with bipolar disorder than in the comparison cohort. Furthermore, female gender is a risk factor for acquisition of STIs (HR = 2.36, 95% CI 1.73-4.89) among patients with bipolar disorder. For individual STIs, the results indicated that the patients with bipolar disorder exhibited a markedly higher risk for subsequently contracting syphilis, genital warts, and trichomoniasis. Bipolar disorder might increase the risk of subsequent newly diagnosed STIs, including syphilis, genital warts, and trichomoniasis. Clinicians should pay particular attention to STIs in patients with bipolar disorder. Patients with bipolar disorder, especially those with a history of high-risk sexual behaviors, should be routinely screened for STIs. We identified patients who were diagnosed with bipolar disorder in the Taiwan National Health Insurance Research Database. A comparison cohort was constructed of patients without bipolar disorder who were matched with the bipolar cohort according to age and gender. The occurrence of subsequent new-onset STIs was evaluated in both cohorts.

Patients With Co-Occurring Bipolar Disorder and Posttraumatic Stress Disorder: A Rapid Review of the Literature.

PubMed

Cerimele, Joseph M; Bauer, Amy M; Fortney, John C; Bauer, Mark S

2017-05-01

To summarize the current literature on epidemiology, clinical correlates, and treatment of individuals with co-occurring bipolar disorder and posttraumatic stress disorder (PTSD). We conducted a focused, time-sensitive review called "rapid review" in November 2015, using keyword searches (including keywords bipolar disorder, post-traumatic stress disorder, PTSD, and others) in PubMed for studies of adults with co-occurring bipolar disorder and PTSD. Results were sorted and systematically searched. An article was excluded if it did not describe adult patients with co-occurring PTSD and bipolar disorder or did not report original data on epidemiology, clinical correlates, or treatment. Information on study characteristics including population studied and key findings were extracted onto a data collection tool. Thirty-two articles were included. Over two-thirds of articles reported epidemiology of co-occurring bipolar disorder and PTSD. Prevalence of PTSD among individuals with bipolar disorder ranged from 4% to 40%, with women and those with bipolar I versus bipolar II disorder experiencing higher prevalence of PTSD. Prevalence of bipolar disorder among individuals with PTSD ranged from 6% to 55%. Baseline PTSD or bipolar disorder was associated with incidence of the other illness. Individuals with co-occurring bipolar disorder and PTSD experienced high symptom burden and low quality of life. No studies evaluated prospective treatment of patients with co-occurring bipolar disorder and PTSD. Bipolar disorder and PTSD commonly co-occur and result in greater symptom burden than either condition alone. Few published treatment strategies exist for patients with both conditions. © Copyright 2017 Physicians Postgraduate Press, Inc.

Bariatric surgery in patients with bipolar spectrum disorders: Selection factors, post-operative visit attendance, and weight outcomes

PubMed Central

Friedman, Kelli E.; Applegate, Katherine; Portenier, Dana; McVay, Megan

2017-01-01

Background As many of 3% of bariatric surgery candidates are diagnosed with a bipolar spectrum disorder. Objectives 1) To describe differences between patients with bipolar spectrum disorders who are approved and not approved for surgery by the mental health evaluator. 2) To examine surgical outcomes of patients with bipolar spectrum disorders. Setting Academic medical center, United States. Methods A retrospective record review was conducted of consecutive patients who applied for bariatric surgery between 2004 and 2009. Patients diagnosed with bipolar spectrum disorders who were approved for surgery (n=42) were compared with patients with a bipolar spectrum disorder who were not approved (n=31) and to matched control surgical patients without a bipolar spectrum diagnosis (n=29) on a variety of characteristics and surgical outcomes. Results Of bariatric surgery candidates diagnosed with a bipolar spectrum disorder who applied for surgery, 57% were approved by the psychologist and 48% ultimately had surgery. Patients with a bipolar spectrum disorder who were approved for surgery were less likely to have had a previous psychiatric hospitalizations than those who were not approved for surgery. Bariatric surgery patients diagnosed with a bipolar spectrum disorder were less likely to attend follow-up care appointments 2 or more years post-surgery compared to matched patients without bipolar disorder. Among patients with available data, those with a bipolar spectrum disorder and matched patients had similar weight loss at 12 months (n=21 for bipolar, n=24 for matched controls) and at 2 or more years (mean=51 months; n=11 for bipolar, n=20 for matched controls). Conclusions Patients diagnosed with a bipolar spectrum disorder have a high rate of delay/denial for bariatric surgery based on the psychosocial evaluation and are less likely to attend medical follow-up care 2 or more years post-surgery. Carefully screened patients with bipolar disorder who engage in long-term follow-up care may benefit from bariatric surgery. PMID:28169206

Experimental chloroquine retinopathy.

PubMed

Matsumura, M; Ohkuma, M; Tsukahara, I

1986-01-01

Chloroquine retinopathy was produced experimentally in the eye of the albino corydoras (one of the tropical fish) by daily administration of chloroquine (0.1 mg per os). The enucleated eyes were examined from the 14th day to 3 months after the beginning of drug administration under light and electron microscopy. The first change of retina was the appearance of membraneous cytoplasmic body (MCB) in the cytoplasm of ganglion, amacrine, bipolar and horizontal cells. MCB might be degenerated lysosome. They showed lamellar figures or crystalline lattice-like structures. Secondarily, these MCB appeared in the inner segments of photoreceptor cells. The outer segments of rod cells disappeared, and then those of cone cells. Although photoreceptor cells were diminished in number in advanced degeneration, the cells of inner nuclear layer and ganglion cells were maintained in number. The presence of MCB dose not mean death of cells. The retinal pigment epithelial cells contained MCB in its cytoplasm only in severe degenerative cases, and did not show other remarkable changes. MCB also appeared in the cytoplasm of pericytes of retinal vessels. Chloroquine is considered to damage directly photoreceptor cells most severely.

Bipolar Disorder - Multiple Languages

MedlinePlus

... Russian (Русский) Expand Section Bipolar Disorder (An Introduction) - English PDF Bipolar Disorder (An Introduction) - Русский (Russian) PDF Bipolar Disorder (An Introduction) - English MP3 Bipolar Disorder (An Introduction) - Русский (Russian) MP3 ...

Slope Stability Estimation of the Kościuszko Mound in Cracow

NASA Astrophysics Data System (ADS)

Wrana, Bogumił; Pietrzak, Natalia

2015-06-01

In the paper, the slope stability problem of the Kościuszko Mound in Cracow, Poland is considered. The slope stability analysis was performed using Plaxis FEM program. The outer surface of the mound has complex geometry. The slope of the cone is not uniform in all directions, on the surface of the cone are pedestrian paths. Due to its complicated geometry it was impossible to do computing by Plaxis input pre-procesor. The initial element mesh was generated using Autodesk Autocad 3D and next it was updated by Plaxis program. The soil parameters were adopted in accordance with the detailed geological soil testing performed in 2012. Calculating model includes geogrids. The upper part was covered by MacMat geogrid, while the lower part of the Mound was reinforced using Terramesh Matt geogrid. The slope analysis was performed by successives reduction of φ /c parameters. The total multiplayer ΣMsf is used to define the value of the soil strength parameters. The article presents the results of slope stability before and after the rainfall during 33 days of precipitation in flood of 2010.

A new method for recognizing quadric surfaces from range data and its application to telerobotics and automation

NASA Technical Reports Server (NTRS)

Alvertos, Nicolas; Dcunha, Ivan

1992-01-01

Pose and orientation of an object is one of the central issues in 3-D recognition problems. Most of today's available techniques require considerable pre-processing such as detecting edges or joints, fitting curves or surfaces to segment images, and trying to extract higher order features from the input images. We present a method based on analytical geometry, whereby all the rotation parameters of any quadric surface are determined and subsequently eliminated. This procedure is iterative in nature and was found to converge to the desired results in as few as three iterations. The approach enables us to position the quadric surface in a desired coordinate system, and then to utilize the presented shape information to explicitly represent and recognize the 3-D surface. Experiments were conducted with simulated data for objects such as hyperboloid of one and two sheets, elliptic and hyperbolic paraboloid, elliptic and hyperbolic cylinders, ellipsoids, and quadric cones. Real data of quadric cones and cylinders were also utilized. Both of these sets yielded excellent results.

Design of a soil cutting resistance sensor for application in site-specific tillage.

PubMed

Agüera, Juan; Carballido, Jacob; Gil, Jesús; Gliever, Chris J; Perez-Ruiz, Manuel

2013-05-10

One objective of precision agriculture is to provide accurate information about soil and crop properties to optimize the management of agricultural inputs to meet site-specific needs. This paper describes the development of a sensor equipped with RTK-GPS technology that continuously and efficiently measures soil cutting resistance at various depths while traversing the field. Laboratory and preliminary field tests verified the accuracy of this prototype soil strength sensor. The data obtained using a hand-operated soil cone penetrometer was used to evaluate this field soil compaction depth profile sensor. To date, this sensor has only been tested in one field under one gravimetric water content condition. This field test revealed that the relationships between the soil strength profile sensor (SSPS) cutting force and soil cone index values are assumed to be quadratic for the various depths considered: 0-10, 10-20 and 20-30 cm (r2 = 0.58, 0.45 and 0.54, respectively). Soil resistance contour maps illustrated its practical value. The developed sensor provides accurate, timely and affordable information on soil properties to optimize resources and improve agricultural economy.

Kinematics of Cone-In-Cone Growth, with Implications for Timing and Formation Mechanism

NASA Astrophysics Data System (ADS)

Hooker, J. N.; Cartwright, J. A.

2015-12-01

Cone-in-cone is an enigmatic structure. Similar to many fibrous calcite veins, cone-in-cone is generally formed of calcite and present in bedding-parallel vein-like accumulations within fine-grained rocks. Unlike most fibrous veins, cone-in-cone contains conical inclusions of host-rock material, creating nested, parallel cones throughout. A long-debated aspect of cone-in-cone structures is whether the calcite precipitated with its conical form (primary cone-in-cone), or whether the cones formed afterwards (secondary cone-in-cone). Trace dolomite within a calcite cone-in-cone structure from the Cretaceous of Jordan supports the primary hypothesis. The host sediment is a siliceous mud containing abundant rhombohedral dolomite grains. Dolomite rhombohedra are also distributed throughout the cone-in-cone. The rhombohedra within the cones are randomly oriented yet locally have dolomite overgrowths having boundaries that are aligned with calcite fibers. Evidence that dolomite co-precipitated with calcite, and did not replace calcite, includes (i) preferential downward extension of dolomite overgrowths, in the presumed growth-direction of the cone-in-cone, and (ii) planar, vertical borders between dolomite crystals and calcite fibers. Because dolomite overgrows host-sediment rhombohedra and forms fibers within the cones, it follows that the host-sediment was included within the growing cone-in-cone as the calcite precipitated, and not afterward. The host-sediment was not injected into the cone-in-cone along fractures, as the secondary-origin hypothesis suggests. This finding implies that cone-in-cone in general does not form over multiple stages, and thus has greater potential to preserve the chemical signature of its original precipitation. Because cone-in-cone likely forms before complete lithification of the host, and because the calcite displaces the host material against gravity, this chemical signature can preserve information about early overpressures in fine-grained sediments.

Design and characterization of a three-terminal transcriptional device through polymerase per second.

PubMed

Varadarajan, Prasanna Amur; Del Vecchio, Domitilla

2009-09-01

In this paper, we provide an in silico input-output characterization of a three-terminal transcriptional device employing polymerase per second (PoPS) as input and output. The device is assembled from well-characterized parts of the bacteriophage lambda switch transcriptional circuit. We draw the analogy between voltage and protein concentration and between current and PoPS to demonstrate that the characteristics of the three-terminal transcriptional device are qualitatively similar to those of a bipolar junction transistor (BJT). In particular, as it occurs in a BJT, the device can be tuned to operate either as a linear amplifier or as a switch. When the device operates as a linear amplifier, gains of twofolds can be obtained, which are considerably smaller than those obtained in a BJT (in which 100-fold amplification gains can be reached). This fact suggests that the parts extracted from natural transcriptional systems may be naturally designed mostly to process and store information as opposed to amplify signals.

Meta-Analysis of Amygdala Volumes in Children and Adolescents with Bipolar Disorder

ERIC Educational Resources Information Center

Pfeifer, Jonathan C.; Welge, Jeffrey; Strakowski. Stephen M.; Adler, Caleb M.; Delbello, Melissa P.

2008-01-01

The size of amygdala of bipolar youths and adults is investigated using neuroimaging studies. Findings showed that smaller volumes of amygdala were observed in youths with bipolar youths compared with children and adolescents without bipolar disorder. The structural amygdala abnormalities in bipolar youths are examined further.

The relationship between borderline personality disorder and bipolar disorder

PubMed Central

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

Emotion in Bipolar I Disorder: Implications for Functional and Symptom Outcomes

PubMed Central

Johnson, Sheri L.; Tharp, Jordan A.; Peckham, Andrew D.; McMaster, Kaja J.

2015-01-01

Despite the centrality of emotion disturbance in neurobiological models of bipolar disorder, the behavioral literature has not yet clearly identified the most central aspects of emotion disturbance in bipolar disorder. Toward this aim, we gathered a battery of emotion-related measures in 67 persons diagnosed with bipolar I disorder as assessed with SCID and a well-matched control group of 58 persons without a history of mood disorders. Those with bipolar disorder were interviewed monthly until they achieved remission, and then tested on emotion measures. A subset of 36 participants with bipolar disorder completed symptom severity interviews at 12-month follow-up. Factor analyses indicated four emotion factor scores: Negative Emotion, Positive Emotion, Reappraisal and Suppression. Bivariate analyses suggested that bipolar disorder was tied to a host of emotion disturbances, but multivariate analyses suggested that bipolar disorder was particularly tied to elevations of Negative Emotion. High Negative Emotion, low Positive Emotion, and high Suppression were conjointly related to lower functioning. Reappraisal predicted declines in depression over time for those with bipolar disorder. Findings highlight the importance of considering the overall profile of emotion disturbance in bipolar disorder. Emotion and emotion regulation appear central to a broad range of outcomes in bipolar disorder. PMID:26480234

Toward the definition of a bipolar prodrome: Dimensional predictors of bipolar spectrum disorder in at-risk youth

PubMed Central

Hafeman, Danella M.; Merranko, John; Axelson, David; Goldstein, Benjamin I.; Goldstein, Tina; Monk, Kelly; Hickey, Mary Beth; Sakolsky, Dara; Diler, Rasim; Iyengar, Satish; Brent, David; Kupfer, David; Birmaher, Boris

2016-01-01

Objective We aimed to assess dimensional symptomatic predictors of new-onset bipolar spectrum disorder in youth at familial risk of bipolar disorder (“at-risk” youth). Method Offspring aged 6–18 of parents with bipolar-I/II disorder (n=391) and offspring of community controls (n=248) were recruited without regard to non-bipolar psychopathology. At baseline, 8.4% (33/391) of offspring of bipolar parents had bipolar spectrum; 14.7% (44/299) of offspring with follow-up developed new-onset bipolar spectrum (15 with bipolar-I/II) over eight years. Scales collected at baseline and follow-up were reduced using factor analyses; factors (both at baseline and visit proximal to conversion or last contact) were then assessed as predictors of new-onset bipolar spectrum. Results Relative to community control offspring, at-risk and bipolar offspring had higher baseline levels of anxiety/depression, inattention/disinhibition, externalizing, subsydromal manic, and affective lability symptoms (p<.05). The strongest predictors of new-onset bipolar spectrum were: baseline anxiety/depression, baseline and proximal affective lability, and proximal subsyndromal manic symptoms (p<.05). While affective lability and anxiety/depression were elevated throughout follow-up in those who later developed bipolar spectrum, manic symptoms increased up to the point of conversion. A path analysis supported the hypothesized model that affective lability at baseline predicted new-onset bipolar spectrum, in part, through increased manic symptoms at the visit prior to conversion; earlier parental age of mood disorder onset also significantly increased risk of conversion (p<.001). While youth without anxiety/depression, affective lability, and mania (and with a parent with older age of mood disorder onset) had a 2% predicted chance of conversion to bipolar spectrum, those with all risk factors had a 49% predicted chance of conversion. Conclusions Dimensional measures of anxiety/depression, affective lability, and mania are important predictors of new-onset bipolar spectrum in this population of at-risk youth. These symptoms emerged from among numerous other candidates, underscoring the potential clinical and research utility of these findings. PMID:26892940

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

PubMed

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 be obtained using the proposed interleaved bipolar acquisition and low-rank reconstruction by using the benefits of the bipolar acquisition while reducing the bipolar-gradient issues with a short imaging time. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Colorimetric determinations of lithium levels in drop-volumes of human plasma for monitoring patients with bipolar mood disorder.

PubMed

Qassem, M; Hickey, M; Kyriacou, P A

2016-08-01

Lithium preparations are considered the most reliable form of mood stabilizing medication for patients with Bipolar disorder. Nevertheless, lithium is a toxic element and its therapeutic range is extremely narrow, with levels of 0.61.0 mEq considered normal, whereas levels above 1.5 mEq are toxic. Thus unfortunately, many patients reach toxic levels that lead to unnecessary complications. It is believed that personal monitoring of blood lithium levels would benefit patients taking lithium medication. Therefore, our aim is to develop a personal lithium blood level analyzer for patients with bipolar mood disorder, and we report here our initial results of a colorimetric-based method used to test drop-volumes of human plasma that had been spiked with lithium. It was possible to validate results with standard flame photometry readings. Applying the Partial Least Squares (PLS) method on preprocessed spectra, therapeutic concentrations of lithium in a single drop can be predicted in a rapid manner, and furthermore, the calibration results were used to select effective wavelengths which were employed as inputs in Multiple Linear Regression (MLR). The simplified algorithms of this would prove useful when developing a personal lithium analyzer. Overall, both calibration methods gave high correlation and small error outputs with a R2= 0.99036 and RMSEC = 0.03778, and R2= 0.994148 and RMSEC= 0.0294404, for PLS and MLR methods, respectively. The results show that the spectrophotometric determination of blood lithium levels can be extended beyond laboratory applications and indicate the capability of this testing principle to be employed in a personal monitoring device. Future work will now focus on the technical development of a miniaturized system for measurement of lithium levels in blood with an acceptable level of accuracy and sensitivity.

Overactive lifestyle in patients with fibromyalgia as a core feature of bipolar spectrum disorder.

PubMed

Alciati, Alessandra; Sarzi-Puttini, Piercarlo; Batticciotto, Alberto; Torta, Riccardo; Gesuele, Felice; Atzeni, Fabiola; Angst, Jules

2012-01-01

To test the hypothesis that the premorbid overactivity previously described in subjects with fibromyalgia is a core feature of the manic/hypomanic symptoms characterising bipolar spectrum disorders. 110 consecutive patients with fibromyalgia were assessed for bipolar spectrum disorders using both categorical and dimensional approaches. The first was based on a version of the DSM-IV SCID-CV interview, modified to improve the detection of bipolar spectrum disorders, the second on the hypomania symptom checklist HCL-32, which adopts a dimensional perspective of the manic/hypomanic component of mood by including sub-syndromal hypomania. Both DSM-IV and Zurich criteria diagnosed high rates of bipolar spectrum disorder in patients with fibromyalgia (70% and 86.3%, respectively). Individuals with a major bipolar spectrum disorder (bipolar II disorder) and with a minor bipolar spectrum disorder (subthreshold depression and hypomania) did not differ in their demographic and clinical aspects. Hypomanic symptom counts on the HCL-32 confirmed high estimates of the bipolar spectrum, with 79% of subjects with fibromyalgia scoring 14 (threshold for hypomania) or above. Overactivity reported in previous studies may be considered a core feature of hypomanic symptoms or syndromes comorbid with bipolar spectrum disorders. Major and minor bipolar spectrum disorders are not associated with differences in demographic or clinical characteristics, suggesting that fibromyalgia rather than being related specifically to depression is related to bipolar spectrum disorders and in particular to the hypomania/overactivity component.

Bipolar disorder and substance use disorders. Madrid study on the prevalence of dual disorders/pathology.

PubMed

Arias, Francisco; Szerman, Nestor; Vega, Pablo; Mesías, Beatriz; Basurte, Ignacio; Rentero, David

2017-06-28

Given its prevalence and impact on public health, the comorbidity of bipolar and substance use disorders is one of the most relevant of dual diagnoses. The objective was to evaluate the characteristics of patients from community mental health and substance abuse centres in Madrid. The sample consisted of 837 outpatients from mental health and substance abuse centres. We used the Mini International Neuropsychiatric Interview (MINI) and Personality Disorder Questionnaire (PDQ4+) to evaluate axis I and II disorders. Of these patients, 174 had a lifetime bipolar disorder, 83 had bipolar disorder type I and 91 had type II. Most patients had dual pathology. Of the 208 participants from the mental health centres, 21 had bipolar disorder and 13 (61.9%) were considered dually-diagnosed patients, while 33.2% of non-bipolar patients had a dual diagnoses (p = 0.03). Of the 629 participants from the substance abuse centres, 153 patients (24.3%) had a bipolar diagnosis. Bipolar dual patients had higher rates of alcohol and cocaine dependence than non-bipolar patients. Moreover, age at onset of alcohol use was earlier in bipolar duallydiagnosed patients than in other alcoholics. Bipolar dually-diagnosed patients had higher personality and anxiety disorder comorbidities and greater suicide risk. Thus, alcohol and cocaine are the drugs most associated with bipolar disorder. Given the nature of the study, the type of relationship between these disorders cannot be determined.

High-Voltage-Input Level Translator Using Standard CMOS

NASA Technical Reports Server (NTRS)

Yager, Jeremy A.; Mojarradi, Mohammad M.; Vo, Tuan A.; Blalock, Benjamin J.

2011-01-01

proposed integrated circuit would translate (1) a pair of input signals having a low differential potential and a possibly high common-mode potential into (2) a pair of output signals having the same low differential potential and a low common-mode potential. As used here, "low" and "high" refer to potentials that are, respectively, below or above the nominal supply potential (3.3 V) at which standard complementary metal oxide/semiconductor (CMOS) integrated circuits are designed to operate. The input common-mode potential could lie between 0 and 10 V; the output common-mode potential would be 2 V. This translation would make it possible to process the pair of signals by use of standard 3.3-V CMOS analog and/or mixed-signal (analog and digital) circuitry on the same integrated-circuit chip. A schematic of the circuit is shown in the figure. Standard 3.3-V CMOS circuitry cannot withstand input potentials greater than about 4 V. However, there are many applications that involve low-differential-potential, high-common-mode-potential input signal pairs and in which standard 3.3-V CMOS circuitry, which is relatively inexpensive, would be the most appropriate circuitry for performing other functions on the integrated-circuit chip that handles the high-potential input signals. Thus, there is a need to combine high-voltage input circuitry with standard low-voltage CMOS circuitry on the same integrated-circuit chip. The proposed circuit would satisfy this need. In the proposed circuit, the input signals would be coupled into both a level-shifting pair and a common-mode-sensing pair of CMOS transistors. The output of the level-shifting pair would be fed as input to a differential pair of transistors. The resulting differential current output would pass through six standoff transistors to be mirrored into an output branch by four heterojunction bipolar transistors. The mirrored differential current would be converted back to potential by a pair of diode-connected transistors, which, by virtue of being identical to the input transistors, would reproduce the input differential potential at the output

Prevalences of autoimmune diseases in schizophrenia, bipolar I and II disorder, and controls.

PubMed

Cremaschi, Laura; Kardell, Mathias; Johansson, Viktoria; Isgren, Anniella; Sellgren, Carl M; Altamura, A Carlo; Hultman, Christina M; Landén, Mikael

2017-12-01

Previous studies on the relationship between autoimmune diseases, schizophrenia, and bipolar disorder are mainly based on hospital discharge registers with insufficient coverage of outpatient data. Furthermore, data is scant on the prevalence of autoimmune diseases in bipolar subgroups. Here we estimate the self-reported prevalences of autoimmune diseases in schizophrenia, bipolar disorder type I and II, and controls. Lifetime prevalence of autoimmune diseases was assessed through a structured interview in a sample of 9076 patients (schizophrenia N = 5278, bipolar disorder type I N = 1952, type II N = 1846) and 6485 controls. Comparative analyses were performed using logistic regressions. The prevalence of diabetes type 1 did not differ between groups. Hyperthyroidism, hypothyroidism regardless of lithium effects, rheumatoid arthritis, and polymyalgia rheumatica were most common in bipolar disorder. Systemic lupus erythematosus was less common in bipolar disorder than in the other groups. The rate of autoimmune diseases did not differ significantly between bipolar subgroups. We conclude that prevalences of autoimmune diseases show clear differences between schizophrenia and bipolar disorder, but not between the bipolar subgroups. Copyright © 2017 Elsevier B.V. All rights reserved.

Virginia Woolf, neuroprogression, and bipolar disorder.

PubMed

Boeira, Manuela V; Berni, Gabriela de Á; Passos, Ives C; Kauer-Sant'Anna, Márcia; Kapczinski, Flávio

2017-01-01

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.

Bipolar disorder in adolescence.

PubMed

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.

Differential diagnosis of bipolar disorder and major depressive disorder.

PubMed

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.

Continuous Active Sonar for Undersea Vehicles Final Report: Input of Factor Graphs into the Detection, Classification, and Localization Chain and Continuous Active SONAR in Undersea Vehicles

DTIC Science & Technology

2015-12-31

image from NURP annual report. in X The ray -cone code simulates the CAS signal received after being reflected form two different targets, and...Cm where m, m, ... , 1fn are X ’s parents, and nodes C1, C1, ... , C,, are X ’s children. Image based on (Duda, Hart, & Stork, 2001). The first...Sorenson, 1970). Using the reference (Welch & Bishop, 2006), the procedure for estimating the real state x , of a discrete-time controlled process , will

Analysis of swimming motions.

NASA Technical Reports Server (NTRS)

Gallenstein, J.; Huston, R. L.

1973-01-01

This paper presents an analysis of swimming motion with specific attention given to the flutter kick, the breast-stroke kick, and the breast stroke. The analysis is completely theoretical. It employs a mathematical model of the human body consisting of frustrums of elliptical cones. Dynamical equations are written for this model including both viscous and inertia forces. These equations are then applied with approximated swimming strokes and solved numerically using a digital computer. The procedure is to specify the input of the swimming motion. The computer solution then provides the output displacement, velocity, and rotation or body roll of the swimmer.

Bipolar disorder type I and II show distinct relationships between cortical thickness and executive function.

PubMed

Abé, C; Rolstad, S; Petrovic, P; Ekman, C-J; Sparding, T; Ingvar, M; Landén, M

2018-06-15

Frontal cortical abnormalities and executive function impairment co-occur in bipolar disorder. Recent studies have shown that bipolar subtypes differ in the degree of structural and functional impairments. The relationships between cognitive performance and cortical integrity have not been clarified and might differ across patients with bipolar disorder type I, II, and healthy subjects. Using a vertex-wise whole-brain analysis, we investigated how cortical integrity, as measured by cortical thickness, correlates with executive performance in patients with bipolar disorder type I, II, and controls (N = 160). We found focal associations between executive function and cortical thickness in the medial prefrontal cortex in bipolar II patients and controls, but not in bipolar I disorder. In bipolar II patients, we observed additional correlations in lateral prefrontal and occipital regions. Our findings suggest that bipolar disorder patients show altered structure-function relationships, and importantly that those relationships may differ between bipolar subtypes. The findings are line with studies suggesting subtype-specific neurobiological and cognitive profiles. This study contributes to a better understanding of brain structure-function relationships in bipolar disorder and gives important insights into the neuropathophysiology of diagnostic subtypes. © 2018 The Authors Acta Psychiatrica Scandinavica Published by John Wiley & Sons Ltd.

Relationship between Chinese adjective descriptors of personality and emotional symptoms in young Chinese patients with bipolar disorders.

PubMed

Yu, Enyan; Li, Huihui; Fan, Hongying; Gao, Qianqian; Tan, Yunfei; Lou, Junyao; Zhang, Jie; Wang, Wei

2015-12-01

To investigate whether personality traits are related to emotional symptoms (mania, hypomania, and depression) in Chinese patients with bipolar disorders. Patients with bipolar I and II disorders, and healthy volunteers, were assessed using the Chinese Adjective Descriptors of Personality (CADP) questionnaire, Mood Disorder Questionnaire (MDQ), Hypomanic Checklist (HCL-32), and Plutchik-van Praag Depression Inventory (PVP). Seventy-three patients with bipolar I disorder, 35 with bipolar II disorder and 216 healthy controls were included. Bipolar I and II groups scored significantly higher on MDQ, HCL-32 and PVP scales than controls; the bipolar II group scored lower on the MDQ, but higher on the HCL-32 and PVP than bipolar I. In the bipolar I group, the CADP Intelligent trait (β, 0.25) predicted MDQ; Intelligent (β, -0.24), Agreeable (β, 0.22) and Emotional (β, 0.34) traits predicted PVP. In the bipolar II group, Intelligent (β, 0.22), Agreeable (β, -0.24) and Unsocial (β, 0.31) traits predicted MDQ; Intelligent (β, -0.20), Agreeable (β, -0.31) and Emotional (β, -0.26) traits predicted HCL-32. Four out of five Chinese personality traits were associated with emotional symptoms in patients with bipolar I or II disorder, but displayed different associations depending on disorder type. © The Author(s) 2015.

[Recurrences of bipolar disorders - comparative study of bipolar disorders, recurring depressions and single depressions in a cohort of patients aged over 65 years].

PubMed

Galland, F; Vaille-Perret, E; Gerbaud, L; Jalenques, I

2007-09-01

Bipolar mood disorders, after starting at adulthood, may remain active throughout life, but bipolar disorders may only be revealed in later life. Indeed, Yet few data on bipolar disorders in the elderly have been reported in the litterature. The influence of normal aging on the outcome of the disease as well as the specific prognosis of bipolar disorders in the elderly has occasionally been studied. Eventually Finally, and contrasting with adults, few studies comparing the various subtypes of mood disorders were have been performed in the elderly. We therefore developed a study in patients aged 65 or above, in order to evaluate the course (recurrences) of bipolar disorders, compared to recurring depressions and single depressions, and to determine the influence of recurrences on the outcome of bipolar disorders. Patients aged over 65 years were inpatients admitted to the department of psychiatry in 2000 for one of the three previously mentioned diagnoses according to DSM IV. Retrospective data were collected from medical reports. Prospectively, data were collected from the general practitioner of each patient (relying on telephone calls), before statistical analysis was performed. Our study demonstrates a more severe outcome for bipolar disorders compared to recurring depressions and single depressions. Patients with bipolar disorders have a higher prevalence of psychiatric recurrences. Furthermore, the greater the number of previous relapses (or the longer the duration and intensity of the disease), the higher the risk of future new future recurrences both in bipolar disorders and recurring depressions. An age of onset of bipolar disorders before 60 years and more than 5 in-hospital admissions increase the risk of recurrences. We originally compare the outcome of bipolar disorders in the elderly, to recurring depressions and single depressions. We confirm the fatal outcome of recurrences in bipolar disorders in old age. Bipolar disorders in the elderly should be considered as a real public health care problem: strategies to minimize the number of episodes experienced by patients with bipolar illness must be pursued aggressively throughout life.

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

PubMed

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.e., affecting all emotions and equally present for males and females. The impairment was associated with neurocognition and functional capacity, but not symptom load. Our findings identify pathopsychological factors underlying the functional impairment in bipolar disorder and suggest the consideration of social cognition training as part of the treatment for bipolar disorder.

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

ERIC Educational Resources Information Center

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…

Bipolar Disorder.

PubMed

Miller, Thomas H

2016-06-01

Bipolar disorder is a chronic mental health disorder that is frequently encountered in primary care. Many patients with depression may actually have bipolar disorder. The management of bipolar disorder requires proper diagnosis and awareness or referral for appropriate pharmacologic therapy. Patients with bipolar disorder require primary care management for comorbidities such as cardiovascular and metabolic disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

Laurentide Ice Sheet meltwater and the Atlantic meridional overturning circulation since the last glacial maximum: A view from the Gulf of Mexico

NASA Astrophysics Data System (ADS)

Flower, B. P.; Williams, C.; Brown, E. A.; Hastings, D. W.; Hendricks, J.; Goddard, E. A.

2010-12-01

The influence of ice sheet meltwater on the Atlantic meridional overturning circulation (AMOC) since the last glacial maximum represents an important issue in abrupt climate change. Comparison of Greenland and Antarctic ice core records has revealed a complex interhemispheric linkage and led to different models of ocean circulation including the “bipolar seesaw.” Meltwater input from the Laurentide Ice Sheet has been invoked as a cause of proximal sea-surface temperature (SST) and salinity change in the North Atlantic, and of regional to global climate change via its influence on the AMOC. We present published and new Mg/Ca, Ba/Ca, and δ18O data on the planktic foraminifer Globigerinoides ruber from northern Gulf of Mexico sediment cores that provide detailed records of SST, δ18O of seawater (δ18Osw), and inferred salinity for the 20-8 ka interval. Age control for Orca Basin core MD02-2550 is based on >40 AMS 14C dates on Globigerinoides ruber and documents continuous sedimentation at rates >35 cm/kyr. Early meltwater input is inferred from δ18Osw and Ba/Ca data prior to and during the Mystery Interval, consistent with a high sensitivity to solar insolation and greenhouse forcing. New bulk sediment δ18O data show major spikes reaching -5.5‰ ca. 14.6 and 12.6 ka. We speculate that these excursions represent fine carbonate sediment from Canadian Paleozoic marine carbonates, analogous to detrital carbonate in the North Atlantic which has a δ18O value of -5‰. Partial support for our hypothesis comes from SEM photomicrographs of bulk sediment from this section, which show no coccoliths or foraminifera in contrast to other intervals. The biogenic carbonate flux seems to have been greatly reduced by fine sediment input. Inferred peak meltwater flow appears to have been associated with the Bolling warming and meltwater pulse 1a. Finally, meltwater reduction at the start of the Younger Dryas supports models for a diversion to North Atlantic outlets and AMOC reduction ca. 12.9 ka, but alternatively could represent diminished ice melting. Overall, the relations between Gulf of Mexico meltwater input, Heinrich events, Antarctic warm events, and AMOC variability suggest bipolar warming and enhanced seasonality during meltwater episodes. We formulate a “meltwater capacitor” hypothesis for understanding enhanced seasonality in the North Atlantic region during abrupt climate change.

Bipolar disorder: diagnostic issues.

PubMed

Tiller, John W G; Schweitzer, Isaac

2010-08-16

Bipolar disorders are cyclical mood disorders with clinical features including distinct sustained periods of mood elevation. Briefer (4 days or more), mild episodes of mood elevation define bipolar II disorder; lengthier (7 days or more), more severe episodes (or those requiring hospitalisation), with or without psychotic features, define bipolar I disorder. Depressive periods are more common and lengthier than manic or hypomanic states, and are the main cause of disability. Bipolar depression may respond poorly to antidepressants and these medications may destabilise the illness. The diagnosis of bipolar disorder should be considered when a patient with depression is treatment resistant. Irritability is a common symptom in bipolar disorder, particularly during mixed states (during which patients have features of mood elevation and depression concurrently) or when there is rapid cycling of mood (more than four episodes of mood disorder per year). Alcohol misuse and use of illicit drugs may simulate mood changes in bipolar disorder. Accurate diagnosis and assessment of bipolar disorder is essential for clinical decision making and determining prognosis and treatments.

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

PubMed Central

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 P<0.00001 as a metric for the overall genetic signal in the sample. We next compared this metric with that obtained using each of seven diagnostic subsets of the group with bipolar disorder: Research Diagnostic Criteria (RDC): bipolar I disorder; manic disorder; bipolar II disorder; schizoaffective 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 (P<0.003) compared with that expected in samples of the same size selected randomly from the total bipolar disorder group data-set. The strongest association in this subset of participants with bipolar disorder was at rs4818065 (P = 2.42×10–7). Biological systems implicated included gamma amniobutyric acid (GABA)A receptors. Genes having at least one associated polymorphism at P<10–4 included B3GALTS, A2BP1, GABRB1, AUTS2, BSN, PTPRG, GIRK2 and CDH12. Conclusions Our findings show that individuals with broadly defined bipolar schizoaffective 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

Nationwide lithological interpretation of cone penetration tests using neural networks

NASA Astrophysics Data System (ADS)

van Maanen, Peter-Paul; Schokker, Jeroen; Harting, Ronald; de Bruijn, Renée

2017-04-01

The Geological Survey of the Netherlands (GSN) systematically produces 3D stochastic geological models of the Dutch subsurface. These voxel models are regarded essential in answering subsurface-related questions on, for example, aggregate resource potential, groundwater flow, land subsidence hazard and the planning and realization of large-scale infrastructural works. GeoTOP is the most recent and detailed generation of 3D voxel models. This model describes 3D stratigraphical and lithological variability up to a depth of 50 m using voxels of 100 × 100 × 0.5 m. Currently, visually described borehole samples are the primary input of these large-scale 3D geological models, both when modeling architecture and composition. Although tens of thousands of cone penetration tests (CPTs) are performed each year, mainly in the reconnaissance phase of construction activities, these data are hardly used as geological model input. There are many reasons why it is of interest to utilize CPT data for geological and lithological modeling of the Dutch subsurface, such as: 1) CPTs are more abundant than borehole descriptions, 2) CPTs are cheaper and easier to gather, and 3) CPT data are more quantitative and uniform than visual sample descriptions. This study uses CPTs and the lithological descriptions of associated nearby undisturbed drilling cores collected by the GSN to establish a nationwide reference dataset for physical and chemical properties of the shallow subsurface. The 167 CPT-core pairs were collected at 160 locations situated in the North, West and South of the Netherlands. These locations were chosen to cover the full extent of geological units and lithological composition in the upper 30 to 40 m of the subsurface in these areas. The distance between the CPT location and associated borehole is small, varying between 0 and 30 m, with an average of 6 m. For each 2 cm CPT interval the data was automatically annotated with the lithoclass from the associated core using a lithological classification script that is also used in GeoTOP to classify the visual sample descriptions. Based on this data a three-layer feedforward neural network was trained containing 5 different inputs: cone resistance, friction ratio, coordinates x and y, and interval depth z. Previous training attempts showed an increased performance when using additional inputs such as pore water pressure, but since these variables are not measured in the majority of CPTs, these were left out in the training procedure. The Newton conjugate-gradient algorithm was applied to train the network. 20-Fold cross-validation yielded 20 different trained nets and independent performance outcomes. Significant performance increase was found as compared to performances of conventional lithological classification charts. A similar neural network was then applied to new CPT data from a pilot area in the city of Rotterdam. This area has a limited number of visual sample descriptions and therefore, additional lithological information of the subsurface is desirable. The results of an evaluation of the neural network's outcomes in this area by geological experts are positive, which paves the way for future nationwide application of this method.

Development and validation of a screening instrument for bipolar spectrum disorder: the Mood Disorder Questionnaire.

PubMed

Hirschfeld, R M; Williams, J B; Spitzer, R L; Calabrese, J R; Flynn, L; Keck, P E; Lewis, L; McElroy, S L; Post, R M; Rapport, D J; Russell, J M; Sachs, G S; Zajecka, J

2000-11-01

Bipolar spectrum disorders, which include bipolar I, bipolar II, and bipolar disorder not otherwise specified, frequently go unrecognized, undiagnosed, and untreated. This report describes the validation of a new brief self-report screening instrument for bipolar spectrum disorders called the Mood Disorder Questionnaire. A total of 198 patients attending five outpatient clinics that primarily treat patients with mood disorders completed the Mood Disorder Questionnaire. A research professional, blind to the Mood Disorder Questionnaire results, conducted a telephone research diagnostic interview by means of the bipolar module of the Structured Clinical Interview for DSM-IV. A Mood Disorder Questionnaire screening score of 7 or more items yielded good sensitivity (0.73) and very good specificity (0.90). The Mood Disorder Questionnaire is a useful screening instrument for bipolar spectrum disorder in a psychiatric outpatient population.

Differential pattern of semantic memory organization between bipolar I and II disorders.

PubMed

Chang, Jae Seung; Choi, Sungwon; Ha, Kyooseob; Ha, Tae Hyon; Cho, Hyun Sang; Choi, Jung Eun; Cha, Boseok; Moon, Eunsoo

2011-06-01

Semantic cognition is one of the key factors in psychosocial functioning. The aim of this study was to explore the differences in pattern of semantic memory organization between euthymic patients with bipolar I and II disorders using the category fluency task. Study participants included 23 euthymic subjects with bipolar I disorder, 23 matched euthymic subjects with bipolar II disorder and 23 matched control subjects. All participants were assessed for verbal learning, recall, learning strategies, and fluency. The combined methods of hierarchical clustering and multidimensional scaling were used to compare the pattern of semantic memory organization among the three groups. Quantitative measures of verbal learning, recall, learning strategies, and fluency did not differ between the three groups. A two-cluster structure of semantic memory organization was identified for the three groups. Semantic structure was more disorganized in the bipolar I disorder group compared to the bipolar II disorder. In addition, patients with bipolar II disorder used less elaborate strategies of semantic memory organization than those of controls. Compared to healthy controls, strategies for categorization in semantic memory appear to be less knowledge-based in patients with bipolar disorders. A differential pattern of semantic memory organization between bipolar I and II disorders indicates a higher risk of cognitive abnormalities in patients with bipolar I disorder compared to patients with bipolar II disorder. Exploring qualitative nature of neuropsychological domains may provide an explanatory insight into the characteristic behaviors of patients with bipolar disorders. Copyright © 2011 Elsevier Inc. All rights reserved.

Suprasensory phenomena in those with a bipolar disorder.

PubMed

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.

Improving the Recognition of Borderline Personality Disorder in a Bipolar World.

PubMed

Zimmerman, Mark

2016-06-01

Both bipolar disorder and borderline personality disorder (BPD) are serious mental health disorders resulting in significant psychosocial morbidity, reduced health-related quality of life, and excess mortality. Yet research on BPD has received much less funding from the National Institute of Health (NIH) than has bipolar disorder during the past 25 years. Why hasn't the level of NIH research funding for BPD been commensurate with the level of psychosocial morbidity, mortality, and health expenditures associated with the disorder? In the present article, the author illustrates how the bipolar disorder research community has done a superior job of "marketing" their disorder. Studies of underdiagnosis, screening, diagnostic spectra, and economics are reviewed for both bipolar disorder and BPD. Researchers of bipolar disorder have conducted multiple studies highlighting the problem with underdiagnosis, developed and promoted several screening scales, published numerous studies of the operating characteristics of these screening measures, attempted to broaden the definition of bipolar disorder by advancing the concept of the bipolar spectrum, and repeatedly demonstrated the economic costs and public health significance of bipolar disorder. In contrast, researchers of BPD have almost completely ignored each of these four issues and research efforts. Although BPD is as frequent as (if not more frequent than) bipolar disorder, as impairing as (if not more impairing than) bipolar disorder, and as lethal as (if not more lethal than) bipolar disorder, it has received less than one-tenth the level of funding from the NIH and has been the focus of many fewer publications in the most prestigious psychiatric journals. The researchers of BPD should consider adopting the strategy taken by researchers of bipolar disorder before the diagnosis is eliminated in a future iteration of the DSM or the ICD.

A prospective study of diagnostic conversion of major depressive disorder to bipolar disorder in pregnancy and postpartum.

PubMed

Sharma, Verinder; Xie, Bin; Campbell, M Karen; Penava, Debbie; Hampson, Elizabeth; Mazmanian, Dwight; Pope, Carley J

2014-02-01

The aim of the present study was to determine the rate of, and risk factors for, a change in diagnosis from major depressive disorder to bipolar disorder, and from bipolar II disorder to bipolar I disorder in pregnancy and postpartum. Patients with a prior history of major depressive disorder or bipolar II disorder were recruited between 24 and 28 weeks' gestation and followed through to one year postpartum. Diagnostic interviews were conducted using the Structured Clinical Interview for DSM-IV at study intake and repeated using the Mini-International Psychiatric Interview at one, three, six, and 12 months after childbirth. Fisher's exact test was used to assess the association between various risk factors and diagnostic switch. A total of 146 participants completed the intake interview and at least one follow-up interview postpartum. Of these, 92 were diagnosed with major depressive disorder and 54 with bipolar II disorder at intake. Six women (6.52%) experienced a diagnostic change from major depressive disorder to bipolar II disorder during the first six months after childbirth. There were no cases of switching to bipolar I disorder, but in one participant the diagnosis changed from bipolar II disorder to bipolar I disorder during the three months after childbirth. Bipolar switch was associated with a family history of bipolar disorder. The postpartum period appears to be a time of high risk for a new onset of hypomania in women with major depressive disorder. Our rate of diagnostic switching to bipolar II disorder (6.52%) is at least 11- to 18-fold higher than the rates of switching in similar studies conducted in both men and women. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Comorbid substance use disorders among youth with bipolar disorder: opportunities for early identification and prevention.

PubMed

Goldstein, Benjamin I; Bukstein, Oscar G

2010-03-01

The burden of substance use disorders (SUDs) among adults with bipolar disorder is well documented. Comparatively less is known regarding comorbid SUD among youth with bipolar disorder. This article aims to integrate the extant literature on this topic and to suggest strategies for delaying or preventing SUD among youth with bipolar disorder. Relevant studies in English were identified using PubMed and MEDLINE (1950-February 2009). Search terms were bipolar disorder cross-referenced with child, adolescent, or youth, and alcohol, drug, or substance, and abuse, dependence, or disorder. Articles were selected on the basis of containing data regarding both bipolar disorder and SUD. The search was supplemented by manually reviewing reference lists from the identified publications. Epidemiologic and clinical studies demonstrate that youth-onset bipolar disorder confers even greater risk of SUD in comparison with adult-onset bipolar disorder. Recent studies of youth with bipolar disorder have not identified childhood SUD (0%); however, the prevalence of SUD escalates during adolescence (16%-39%). Substance use disorder among bipolar youth is associated with legal and academic difficulties, pregnancy, and suicidality. Few studies have addressed interventions for this population, although studies are underway. Because bipolar disorder onset most commonly precedes SUD among youth (55%-83%), there is a window of opportunity for prevention. Pending the results of ongoing treatment studies, several strategies are suggested for curtailing the burden of SUD in youth with bipolar disorder. These include screening for substance use among bipolar youth beginning at age 10 irrespective of other risk factors, education and intervention at the family level, and implementation of preventive interventions that have been successful in other populations. (c) 2010 Physicians Postgraduate Press, Inc.

The bipolar II disorder personality traits, a true syndrome?

PubMed

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.

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

PubMed

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.

Change in employment status in bipolar disorder: a longitudinal study using national claims data.

PubMed

Chang, Hui-Chih; Huang, Kuan-Chih; Chiu, Wei-Che; Huang, Kuo-Cherh; Tang, Chao-Hsiun; Su, Kuan-Pin

2016-04-01

To assess change in employment status in patients with bipolar disorder in comparison with non-mentally ill controls from 1 year before bipolar incidence to 10 years after. Sociodemographic factors of change in employment status were also examined for patients with bipolar disorder. A cohort of 502 patients with ICD-9-CM bipolar disorder was identified using claims data from the National Health Insurance Research Database of Taiwan between 1998 and 2001 and compared to non-mentally ill controls through December 31, 2008. The primary outcome measure was the time from bipolar incidence to the time of change in employment status, ie, from earning income to not earning income. The probability of changing to a non-income earner was significantly higher (P < .0001) in patients with bipolar disorder than in controls over time, even before the incidence of bipolar disorder (27% vs 14% for patients with bipolar disorder vs controls, respectively). Risks of occupational deterioration in patients with bipolar disorder were greater in the year before incidence and in the following year, with gradually decreasing risks over the subsequent 2 years, and comparable to controls from the third year onward. The adjusted hazard ratio of changing to a non-income earner was 2.06 (95% CI, 1.82-2.33) in patients with bipolar disorder. Male sex, ages 18 to 25 years, lower payroll bracket (< NT$50,001 [US $1,489]), and living in an urban area and insured area in the Northern region were associated with the risk of changing to a non-income earner in patients with bipolar disorder. Patients with bipolar disorder had poorer employment outcomes than the controls, with greater risks of occupational deterioration before and after the bipolar episodes. Employment status should be incorporated as a measure of functioning and of treatment and intervention effectiveness in clinical practices and research. © Copyright 2016 Physicians Postgraduate Press, Inc.

Individuals with bipolar disorder and their relationship with the criminal justice system: a critical review.

PubMed

Fovet, Thomas; Geoffroy, Pierre Alexis; Vaiva, Guillaume; Adins, Catherine; Thomas, Pierre; Amad, Ali

2015-04-01

Bipolar disorder is a severe and prevalent psychiatric disease. Poor outcomes include a high frequency of criminal acts, imprisonments, and repeat offenses. This critical review of the international literature examined several aspects of the complex relationship between individuals with bipolar disorder and the criminal justice system: risk factors for criminal acts, features of bipolar patients' incarceration, and their postrelease trajectories. Publications were obtained from the PubMed and Google Scholar electronic databases by using the following MeSH headings: prison, forensic psychiatry, criminal law, crime, and bipolar disorder. Among patients with bipolar disorder, the frequency of violent criminal acts is higher than in the general population (odds ratio [OR]=2.8, 95% confidence interval [CI]=1.8-4.3). The frequency is higher among patients with bipolar disorder and a comorbid substance use disorder than among those without either disorder (OR=10.1, CI=5.3-19.2). As a result, the prevalence of bipolar disorder among prisoners is high (2%-7%). In prison, patients' bipolar disorder symptoms can complicate their relationship with prison administrators, leading to an increased risk of multiple incarcerations. Moreover, the risk of suicide increases for these prisoners. Criminal acts are common among patients with bipolar disorder and are often associated with problems such as addiction. Thus it is important to improve the diagnosis and treatment of inmates with bipolar disorder.

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

PubMed

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.

Creativity and bipolar disorder: Touched by fire or burning with questions?☆

PubMed Central

Johnson, Sheri L.; Murray, Greg; Fredrickson, Barbara; Youngstrom, Eric A.; Hinshaw, Stephen; Bass, Julie Malbrancq; Deckersbach, Thilo; Schooler, Jonathan; Salloum, Ihsan

2012-01-01

Substantial literature has linked bipolar disorder with creative accomplishment. Much of the thinking in this area has been inspired by biographical accounts of poets, musicians, and other highly accomplished groups, which frequently document signs of bipolar disorder in these samples. A smaller literature has examined quantitative measures of creativity among people with bipolar disorder or at risk for the disorder. In this paper, we provide a critical review of such evidence. We then consider putative mechanisms related to the link of bipolar disorder with creativity, by drawing on literature outside of bipolar disorder on personality, motivational, and affective predictors of creativity. Because so little research has directly evaluated whether these factors could help explain the elevations of creativity in bipolar disorder, we conclude with an agenda for future research on the theoretically and clinically compelling topic of creativity in bipolar disorder. PMID:22088366

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.

PubMed

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

2015-09-01

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. 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. 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. 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 stronger prospective data on treatment options are required before more decisive conclusions can be made regarding the neurobiology and specific treatment of suicide risk in bipolar disorder. © The Royal Australian and New Zealand College of Psychiatrists 2015.

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

PubMed Central

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 stronger prospective data on treatment options are required before more decisive conclusions can be made regarding the neurobiology and specific treatment of suicide risk in bipolar disorder. PMID:26185269

Excessive and premature new-onset cardiovascular disease among adults with bipolar disorder in the US NESARC cohort.

PubMed

Goldstein, Benjamin I; Schaffer, Ayal; Wang, Shuai; Blanco, Carlos

2015-02-01

Cross-sectional studies demonstrate increased prevalence of cardiovascular disease (CVD) among adults with bipolar disorder. However, there is a paucity of prospective data regarding new-onset CVD among adults with bipolar disorder. Analyses compared the 3-year incidence of CVD (via participant-reported physician diagnoses) among participants with DSM-IV diagnoses of bipolar I disorder (n = 1,047), bipolar II disorder (n = 392), major depressive disorder (MDD; n = 4,396), or controls (n = 26,266), who completed Wave 1 (2001-2002) and Wave 2 (2004-2005) of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Analyses also compared the age of participants with new-onset CVD across groups. Multivariable analyses controlled for age, sex, race, cigarette smoking, hypertension, obesity, and alcohol and drug use disorders. The 3-year incidence of CVD among adults with bipolar I disorder, bipolar II disorder, MDD, and among controls was 6.30%, 5.74%, 3.98%, and 3.70%, respectively. The covariate-adjusted incidence of CVD was significantly greater among participants with bipolar I and II disorders versus controls and versus participants with MDD. Adjusted odds ratios (95% CI) were 2.58 (1.84-3.61; P < .0001) for bipolar I disorder vs controls; 2.76 (1.60-4.74; P = .0004) for bipolar II disorder vs controls; 2.11 (1.46-3.04; P = .0001) for bipolar I disorder vs MDD; 2.25 (1.26-4.01; P = .007) for bipolar II disorder vs MDD; and 1.22 (0.99-1.51; P = .06) for MDD vs controls. Bipolar I disorder participants with new-onset CVD were 10.70 ± 2.77 years younger than MDD participants with new-onset CVD and 16.78 ± 2.51 years younger than controls. Bipolar II disorder participants with new-onset CVD were 7.92 ± 3.27 years younger than MDD participants with new-onset CVD and 13.99 ± 2.79 years younger than controls. Adults with bipolar disorder are at significantly and meaningfully increased risk to develop CVD over the course of 3 years, even as compared to adults with MDD, and despite controlling for multiple potential confounds. Combined with very early age of CVD onset, this finding underscores the need for early and assertive CVD prevention strategies for people with bipolar disorder. © Copyright 2015 Physicians Postgraduate Press, Inc.

Interactions between bipolar disorder and antisocial personality disorder in trait impulsivity and severity of illness.

PubMed

Swann, A C; Lijffijt, M; Lane, S D; Steinberg, J L; Moeller, F G

2010-06-01

We investigated trait impulsivity in bipolar disorder and antisocial personality disorder (ASPD) with respect to severity and course of illness. Subjects included 78 controls, 34 ASPD, 61 bipolar disorder without Axis II disorder, and 24 bipolar disorder with ASPD, by Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) (SCID-I and -II). Data were analyzed using general linear model and probit analysis. Barratt Impulsiveness Scale (BIS-11) scores were higher in ASPD (effect sizes 0.5-0.8) or bipolar disorder (effect size 1.45) than in controls. Subjects with both had more suicide attempts and previous episodes than bipolar disorder alone, and more substance-use disorders and suicide attempts than ASPD alone. BIS-11 scores were not related to severity of crimes. Impulsivity was higher in bipolar disorder with or without ASPD than in ASPD alone, and higher in ASPD than in controls. Adverse effects of bipolar disorder in ASPD, but not of ASPD in bipolar disorder, were accounted for by increased impulsivity.

Are "social drugs" (tobacco, coffee and chocolate) related to the bipolar spectrum?

PubMed

Maremmani, Icro; Perugi, Giulio; Rovai, Luca; Maremmani, Angelo Giovanni Icro; Pacini, Matteo; Canonico, Pier Luigi; Carbonato, Paolo; Mencacci, Claudio; Muscettola, Giovanni; Pani, Luca; Torta, Riccardo; Vampini, Claudio; Akiskal, Hagop S

2011-09-01

Across all ages and cultures, mankind has always used substances in order to induce pleasurable sensations or desirable psychophysical states. These substances, notably caffeine, tobacco, alcohol and chocolate, can be labeled 'social drugs'. We analyzed the social drug habits of 562 patients suffering from mood disorders, according to DSM-IV-R criteria (major depressive episode, recurrent depression, bipolar type I and II disorders and depression not otherwise specified). The sample was also divided into bipolar and non-bipolar according to Hypomania Check-list 32 (HCL-32), which proposes a broader concept of hypomania and soft bipolarity, comprising the spectrum of bipolar disorders proper, along with other, "softer" expressions of bipolarity intermediate between bipolar disorder and normality. Using HCL-32 criteria, but DSM-IV-R criteria, a link was confirmed between bipolar spectrum and substance use including social drugs such as tobacco and coffee. Observational correlational study. This study is in support of earlier theoretical formulations within the framework of the Pisa-San Diego collaboration. Copyright © 2011 Elsevier B.V. All rights reserved.

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

PubMed

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.

Cryogenic ultra-low-noise SiGe transistor amplifier.

PubMed

Ivanov, B I; Trgala, M; Grajcar, M; Il'ichev, E; Meyer, H-G

2011-10-01

An ultra-low-noise one-stage SiGe heterojunction bipolar transistor amplifier was designed for cryogenic temperatures and a frequency range of 10 kHz-100 MHz. A noise temperature T(N) ≈ 1.4 K was measured at an ambient temperature of 4.2 K at frequencies between 100 kHz and 100 MHz for a source resistance of ~50 Ω. The voltage gain of the amplifier was 25 dB at a power consumption of 720 μW. The input voltage noise spectral density of the amplifier is about 35 pV/√Hz. The low noise resistance and power consumption makes the amplifier suitable for readout of resistively shunted DC SQUID magnetometers and amplifiers.

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

Russell, Steven J.; Carlsten, Bruce E.

We will quickly go through the history of the non-linear transmission lines (NLTLs). We will describe how they work, how they are modeled and how they are designed. Note that the field of high power, NLTL microwave sources is still under development, so this is just a snap shot of their current state. Topics discussed are: (1) Introduction to solitons and the KdV equation; (2) The lumped element non-linear transmission line; (3) Solution of the KdV equation; (4) Non-linear transmission lines at microwave frequencies; (5) Numerical methods for NLTL analysis; (6) Unipolar versus bipolar input; (7) High power NLTL pioneers;more » (8) Resistive versus reactive load; (9) Non-lineaer dielectrics; and (10) Effect of losses.« less

Fast and robust shape diameter function.

PubMed

Chen, Shuangmin; Liu, Taijun; Shu, Zhenyu; Xin, Shiqing; He, Ying; Tu, Changhe

2018-01-01

The shape diameter function (SDF) is a scalar function defined on a closed manifold surface, measuring the neighborhood diameter of the object at each point. Due to its pose oblivious property, SDF is widely used in shape analysis, segmentation and retrieval. However, computing SDF is computationally expensive since one has to place an inverted cone at each point and then average the penetration distances for a number of rays inside the cone. Furthermore, the shape diameters are highly sensitive to local geometric features as well as the normal vectors, hence diminishing their applications to real-world meshes which often contain rich geometric details and/or various types of defects, such as noise and gaps. In order to increase the robustness of SDF and promote it to a wide range of 3D models, we define SDF by offsetting the input object a little bit. This seemingly minor change brings three significant benefits: First, it allows us to compute SDF in a robust manner since the offset surface is able to give reliable normal vectors. Second, it runs many times faster since at each point we only need to compute the penetration distance along a single direction, rather than tens of directions. Third, our method does not require watertight surfaces as the input-it supports both point clouds and meshes with noise and gaps. Extensive experimental results show that the offset-surface based SDF is robust to noise and insensitive to geometric details, and it also runs about 10 times faster than the existing method. We also exhibit its usefulness using two typical applications including shape retrieval and shape segmentation, and observe a significant improvement over the existing SDF.

Experimental investigation on pressurization performance of cryogenic tank during high-temperature helium pressurization process

NASA Astrophysics Data System (ADS)

Lei, Wang; Yanzhong, Li; Yonghua, Jin; Yuan, Ma

2015-03-01

Sufficient knowledge of thermal performance and pressurization behaviors in cryogenic tanks during rocket launching period is of importance to the design and optimization of a pressurization system. In this paper, ground experiments with liquid oxygen (LO2) as the cryogenic propellant, high-temperature helium exceeding 600 K as the pressurant gas, and radial diffuser and anti-cone diffuser respectively at the tank inlet were performed. The pressurant gas requirements, axial and radial temperature distributions, and energy distributions inside the propellant tank were obtained and analyzed to evaluate the comprehensive performance of the pressurization system. It was found that the pressurization system with high-temperature helium as the pressurant gas could work well that the tank pressure was controlled within a specified range and a stable discharging liquid rate was achieved. For the radial diffuser case, the injected gas had a direct impact on the tank inner wall. The severe gas-wall heat transfer resulted in about 59% of the total input energy absorbed by the tank wall. For the pressurization case with anti-cone diffuser, the direct impact of high-temperature gas flowing toward the liquid surface resulted in a greater deal of energy transferred to the liquid propellant, and the percentage even reached up to 38%. Moreover, both of the two cases showed that the proportion of energy left in ullage to the total input energy was quite small, and the percentage was only about 22-24%. This may indicate that a more efficient diffuser should be developed to improve the pressurization effect. Generally, the present experimental results are beneficial to the design and optimization of the pressurization system with high-temperature gas supplying the pressurization effect.

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

PubMed

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.

Real-time emulation of neural images in the outer retinal circuit.

PubMed

Hasegawa, Jun; Yagi, Tetsuya

2008-12-01

We describe a novel real-time system that emulates the architecture and functionality of the vertebrate retina. This system reconstructs the neural images formed by the retinal neurons in real time by using a combination of analog and digital systems consisting of a neuromorphic silicon retina chip, a field-programmable gate array, and a digital computer. While the silicon retina carries out the spatial filtering of input images instantaneously, using the embedded resistive networks that emulate the receptive field structure of the outer retinal neurons, the digital computer carries out the temporal filtering of the spatially filtered images to emulate the dynamical properties of the outer retinal circuits. The emulations of the neural image, including 128 x 128 bipolar cells, are carried out at a frame rate of 62.5 Hz. The emulation of the response to the Hermann grid and a spot of light and an annulus of lights has demonstrated that the system responds as expected by previous physiological and psychophysical observations. Furthermore, the emulated dynamics of neural images in response to natural scenes revealed the complex nature of retinal neuron activity. We have concluded that the system reflects the spatiotemporal responses of bipolar cells in the vertebrate retina. The proposed emulation system is expected to aid in understanding the visual computation in the retina and the brain.

Electrophysiology of pumpkin seeds: Memristors in vivo.

PubMed

Volkov, Alexander G; Nyasani, Eunice K; Tuckett, Clayton; Greeman, Esther A; Markin, Vladislav S

2016-01-01

Leon Chua, the discoverer of a memristor, theoretically predicted that voltage gated ion channels can be memristors. We recently found memristors in different plants such as the Venus flytrap, Mimosa pudica, Aloe vera, apple fruits, and in potato tubers. There are no publications in literature about the existence of memristors in seeds. The goal of this work was to discover if pumpkin seeds might have memristors. We selected Cucurbita pepo L., cv. Cinderella, Cucurbita maxima L. cv Warty Goblin, and Cucurbita maxima L., cv. Jarrahdale seeds for this analysis. In these seeds, we found the presence of resistors with memory. The analysis was based on cyclic voltammetry where a memristor should manifest itself as a nonlinear two-terminal electrical element, which exhibits a pinched hysteresis loop on a current-voltage plane for any bipolar cyclic voltage input signal. Dry dormant pumpkin seeds have very high electrical resistance without memristive properties. The electrostimulation by bipolar sinusoidal or triangular periodic waves induces electrical responses in imbibed pumpkin seeds with fingerprints of memristors. Tetraethylammonium chloride, an inhibitor of voltage gated K(+) channels, transforms a memristor to a resistor in pumpkin seeds. NPPB (5-Nitro-2-(3-phenylpropylamino)benzoic acid) inhibits the memristive properties of imbibed pumpkin seeds. The discovery of memristors in pumpkin seeds creates a new direction in the understanding of electrophysiological phenomena in seeds.

Normal Perceptual Sensitivity Arising From Weakly Reflective Cone Photoreceptors

PubMed Central

Bruce, Kady S.; Harmening, Wolf M.; Langston, Bradley R.; Tuten, William S.; Roorda, Austin; Sincich, Lawrence C.

2015-01-01

Purpose To determine the light sensitivity of poorly reflective cones observed in retinas of normal subjects, and to establish a relationship between cone reflectivity and perceptual threshold. Methods Five subjects (four male, one female) with normal vision were imaged longitudinally (7–26 imaging sessions, representing 82–896 days) using adaptive optics scanning laser ophthalmoscopy (AOSLO) to monitor cone reflectance. Ten cones with unusually low reflectivity, as well as 10 normally reflective cones serving as controls, were targeted for perceptual testing. Cone-sized stimuli were delivered to the targeted cones and luminance increment thresholds were quantified. Thresholds were measured three to five times per session for each cone in the 10 pairs, all located 2.2 to 3.3° from the center of gaze. Results Compared with other cones in the same retinal area, three of 10 monitored dark cones were persistently poorly reflective, while seven occasionally manifested normal reflectance. Tested psychophysically, all 10 dark cones had thresholds comparable with those from normally reflecting cones measured concurrently (P = 0.49). The variation observed in dark cone thresholds also matched the wide variation seen in a large population (n = 56 cone pairs, six subjects) of normal cones; in the latter, no correlation was found between cone reflectivity and threshold (P = 0.0502). Conclusions Low cone reflectance cannot be used as a reliable indicator of cone sensitivity to light in normal retinas. To improve assessment of early retinal pathology, other diagnostic criteria should be employed along with imaging and cone-based microperimetry. PMID:26193919

Nutrition and Bipolar Depression.

PubMed

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.

Review of Evidence for Use of Antidepressants in Bipolar Depression

PubMed Central

McInerney, Shane J.

2014-01-01

Objective: Depressive episodes predominate over the course of bipolar disorder and cause considerable functional impairment. Antidepressants are frequently prescribed in the treatment of bipolar depression, despite concerns about efficacy and risk of switching to mania. This review provides a critical examination of the evidence for and against the use of antidepressants in bipolar depression. Data Sources: English-language peer-reviewed literature and evidence-based guidelines published between January 1, 1980, and March 2014, were identified using PubMed, MEDLINE, PsycINFO/PsycLIT, and EMBASE. All searches contained the terms antidepressants, bipolar depression, depressive episodes in bipolar disorder, and treatment guidelines for bipolar depression. Meta-analyses, randomized controlled trials, systematic reviews, and practice guidelines were included. Bibliographies from these publications were used to identify additional articles of interest. Data Extraction: Studies involving treatment of bipolar depression with antidepressant monotherapy, adjunctive use of antidepressant with a mood stabilizer, and meta-analysis of such studies combined were reviewed. Conclusions: The body of evidence on the use of antidepressant monotherapy to treat patients with bipolar depression is contentious, but the recommendations from evidence-based guidelines do not support antidepressant monotherapy for bipolar depression. Only when mood stabilizer or atypical antipsychotic monotherapy has failed should adjunctive treatment with an antidepressant be considered. PMID:25667812

The electrolysis time on electrosynthesis of hydroxyapatite with bipolar membrane

NASA Astrophysics Data System (ADS)

Nur, Adrian; Jumari, Arif; Budiman, Anatta Wahyu; Puspitaningtyas, Stella Febianti; Cahyaningrum, Suci; Nazriati, Nazriati; Fajaroh, Fauziatul

2018-02-01

The electrochemical method with bipolar membrane has been successfully used for the synthesis of hydroxyapatite. In this work, we have developed 2 chambers electrolysis system separated by a bipolar membrane. The membrane was used to separate cations (H+ ions produced by the oxidation of water at the anode) and anions (OH- ions produced by the reduction of water at the cathode). With this system, we have designed that OH- ions still stay in the anions chamber because OH- ions was very substantial in the hydroxyapatite particles formation. The aim of this paper was to compare the electrolysis time on electrosynthesis of hydroxyapatite with and without the bipolar membrane. The electrosynthesis was performed at 500 mA/cm2 for 0.5 to 2 hours at room temperature and under ultrasonic cleaner to void agglomeration with and without the bipolar membrane. The electrosynthesis of hydroxyapatite with the bipolar membrane more effective than without the bipolar membrane. The hydroxyapatite has been appeared at 0.5 h of the electrolysis time with the bipolar membrane (at the cathode chamber) while it hasn't been seen without the bipolar membrane. The bipolar membrane prevents OH- ions migrate to the cation chamber. The formation of HA becomes more effective because OH- ions just formed HA particle.

Psychotic and Bipolar Disorders: Bipolar Disorder.

PubMed

Holder, Sarah D

2017-04-01

Bipolar disorder is a severe chronic mental illness that affects a large number of individuals. This disorder is separated into two major types, bipolar I disorder, with mania and typically recurrent depression, and bipolar II disorder, with recurrent major depression and hypomania. Patients with bipolar disorder spend the majority of time experiencing depression, and this typically is the presenting symptom. Because outcomes are improved with earlier diagnosis and treatment, physicians should maintain a high index of suspicion for bipolar disorder. The most effective long-term treatments are lithium and valproic acid, although other drugs also are used. In addition to referral to a mental health subspecialist for initiation and management of drug treatment, patients with bipolar disorder should be provided with resources for psychotherapy. Several comorbidities commonly associated with bipolar disorder include other mental disorders, substance use disorders, migraine headaches, chronic pain, stroke, metabolic syndrome, and cardiovascular disease. Family physicians who care for patients with bipolar disorder should focus their efforts on prevention and management of comorbidities. These patients should be assessed continually for risk of suicide because they are at high risk and their suicide attempts tend to be successful. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

Suppressing thyroid hormone signaling preserves cone photoreceptors in mouse models of retinal degeneration

PubMed Central

Ma, Hongwei; Thapa, Arjun; Morris, Lynsie; Redmond, T. Michael; Baehr, Wolfgang; Ding, Xi-Qin

2014-01-01

Cone phototransduction and survival of cones in the human macula is essential for color vision and for visual acuity. Progressive cone degeneration in age-related macular degeneration, Stargardt disease, and recessive cone dystrophies is a major cause of blindness. Thyroid hormone (TH) signaling, which regulates cell proliferation, differentiation, and apoptosis, plays a central role in cone opsin expression and patterning in the retina. Here, we investigated whether TH signaling affects cone viability in inherited retinal degeneration mouse models. Retinol isomerase RPE65-deficient mice [a model of Leber congenital amaurosis (LCA) with rapid cone loss] and cone photoreceptor function loss type 1 mice (severe recessive achromatopsia) were used to determine whether suppressing TH signaling with antithyroid treatment reduces cone death. Further, cone cyclic nucleotide-gated channel B subunit-deficient mice (moderate achromatopsia) and guanylate cyclase 2e-deficient mice (LCA with slower cone loss) were used to determine whether triiodothyronine (T3) treatment (stimulating TH signaling) causes deterioration of cones. We found that cone density in retinol isomerase RPE65-deficient and cone photoreceptor function loss type 1 mice increased about sixfold following antithyroid treatment. Cone density in cone cyclic nucleotide-gated channel B subunit-deficient and guanylate cyclase 2e-deficient mice decreased about 40% following T3 treatment. The effect of TH signaling on cone viability appears to be independent of its regulation on cone opsin expression. This work demonstrates that suppressing TH signaling in retina dystrophy mouse models is protective of cones, providing insights into cone preservation and therapeutic interventions. PMID:24550448

Levels of triglycerides, cholesterol, LDL, HDL and glucose in patients with schizophrenia, unipolar depression and bipolar disorder.

PubMed

Wysokiński, Adam; Strzelecki, Dominik; Kłoszewska, Iwona

2015-01-01

The aim of this study is to investigate differences in triglycerides (TGA), cholesterol (TC), HDL, LDL and glucose (FPG) levels in patients with acute schizophrenia, unipolar depression, bipolar depression and bipolar mania. Results for 2305 Caucasian patients were included in the study (1377 women, 59.7%; mean age 45.6). Mean TGA level was: schizophrenia: 139.9±90.6 mg/dL, unipolar depression: 125.4±70.8 mg/dL, bipolar disorder: 141.1±81.9 mg/dL, bipolar depression: 147.7±82.8 mg/dL mg/dL, bipolar mania: 120.2±76.1 mg/dL, inter-group differences were significant (p<0.001). Mean TC level was: schizophrenia: 188.5±40.4 mg/dL, unipolar depression: 198.8±50.7 mg/dL, bipolar disorder: 194.4±48.3 mg/dL, bipolar depression: 198.9±48.8 mg/dL, bipolar mania: 180.1±43.8 mg/dL, inter-group differences were significant (p<0.001). Mean HDL level was: schizophrenia: 45.3±13.9 mg/dL, unipolar depression: 48.1±14.8 mg/dL, bipolar disorder: 45.4±15.3 mg/dL, bipolar depression: 45.1±15.4 mg/dL, bipolar mania: 46.4±15.1 mg/dL, inter-group differences were significant (p<0.001). Mean LDL level was: schizophrenia: 115.4±34.7 mg/dL, unipolar depression: 125.7±44.1 mg/dL, bipolar disorder: 120.9±42.1 mg/dL, bipolar depression: 124.5±43.1 mg/dL, bipolar mania: 109.3±36.9 mg/dL, inter-group differences were significant (p<0.001). Mean FPG level was: schizophrenia: 95.9±24.9 mg/dL, unipolar depression: 94.8±22.9 mg/dL, bipolar disorder: 97.2±24.4 mg/dL, bipolar depression: 98.3±25.3 mg/dL, bipolar mania: 93.9±21.1 mg/dL, inter-group differences were not significant (p=0.08). Odds ratios for glucose and lipids abnormalities, correlations with age, sex distribution in diagnostic groups for normal ranges of glucose and lipids, differences in glucose and lipids levels between the age groups were also calculated. Our results confirm that there is a high prevalence of lipid and glucose abnormalities in patients with schizophrenia and mood disorders (both unipolar and bipolar). However, we have demonstrated that these diagnostic groups differ in terms of types and frequency of these metabolic dysfunctions. Women and patients aged 40+ are at particularly high risk. Copyright © 2015 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Optic nerve signals in a neuromorphic chip I: Outer and inner retina models.

PubMed

Zaghloul, Kareem A; Boahen, Kwabena

2004-04-01

We present a novel model for the mammalian retina and analyze its behavior. Our outer retina model performs bandpass spatiotemporal filtering. It is comprised of two reciprocally connected resistive grids that model the cone and horizontal cell syncytia. We show analytically that its sensitivity is proportional to the space-constant-ratio of the two grids while its half-max response is set by the local average intensity. Thus, this outer retina model realizes luminance adaptation. Our inner retina model performs high-pass temporal filtering. It features slow negative feedback whose strength is modulated by a locally computed measure of temporal contrast, modeling two kinds of amacrine cells, one narrow-field, the other wide-field. We show analytically that, when the input is spectrally pure, the corner-frequency tracks the input frequency. But when the input is broadband, the corner frequency is proportional to contrast. Thus, this inner retina model realizes temporal frequency adaptation as well as contrast gain control. We present CMOS circuit designs for our retina model in this paper as well. Experimental measurements from the fabricated chip, and validation of our analytical results, are presented in the companion paper [Zaghloul and Boahen (2004)].

INCREASED PROSPECTIVE HEALTH SERVICE USE FOR DEPRESSION AMONG ADULTS WITH CHILDHOOD ONSET BIPOLAR DISORDER

PubMed Central

Sala, Regina; Goldstein, Benjamin I.; Wang, Shuai; Flórez-Salamanca, Ludwing; Iza, Miren; Blanco, Carlos

2013-01-01

Objective To examine the prospective relationship between age of onset of bipolar disorder and the demographic and clinical characteristics, treatment, new onset of psychiatric comorbidity, and psychosocial functioning among adults with bipolar disorder. Study design As part of the National Epidemiologic Survey on Alcohol and Related Conditions, 1600 adults who met lifetime DSM-IV criteria for bipolar disorder-I (n=1172) and bipolar disorder-II (n=428) were included. Individuals were evaluated using the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DMS-IV Version and data was analyzed from Waves 1 and 2, approximately 3 years apart. Individuals with bipolar disorder were divided into three age at onset groups: childhood (<13 years old, n=115), adolescence (13-18 years old, n=396), and adulthood (>19 year old, n=1017). Results After adjusting for confounding factors, adults with childhood-onset bipolar disorder were more likely to see a counselor, have been hospitalized and have received emergency room treatment for depression compared with those with adulthood-onset bipolar disorder. By contrast, there were no differences in the severity of mania or hypomania, new onset of comorbidity, and psychosocial functioning by age of bipolar disorder onset. Conclusions Childhood-onset bipolar disorder is prospectively associated with seeking treatment for depression, an important proxy for depressive severity. Longitudinal studies are needed in order to determine whether prompt identification, accurate diagnosis, and early intervention can serve to mitigate the burden of childhood onset on the long-term depressive burden of bipolar disorder. PMID:23896190

Cone of Darkness: Finding Blank-sky Positions for Multi-object Wide-field Observations

NASA Astrophysics Data System (ADS)

Lorente, N. P. F.

2014-05-01

We present the Cone of Darkness, an application to automatically configure blank-sky positions for a series of stacked, wide-field observations, such as those carried out by the SAMI instrument on the Anglo-Australian Telescope (AAT). The Sydney-AAO Multi-object Integral field spectrograph (SAMI) uses a plug-plate to mount its 13×61 core imaging fibre bundles (hexabundles) in the optical plane at the telescope's prime focus. To make the most efficient use of each plug-plate, several observing fields are typically stacked to produce a single plate. When choosing blank-sky positions for the observations it is most effective to select these such that one set of 26 holes gives valid sky positions for all fields on the plate. However, when carried out manually this selection process is tedious and includes a significant risk of error. The Cone of Darkness software aims to provide uniform blank-sky position coverage over the field of observation, within the limits set by the distribution of target positions and the chosen input catalogs. This will then facilitate the production of the best representative median sky spectrum for use in sky subtraction. The application, written in C++, is configurable, making it usable for a range of instruments. Given the plate characteristics and the positions of target holes, the software segments the unallocated space on the plate and determines the position which best fits the uniform distribution requirement. This position is checked, for each field, against the selected catalog using a TAP ADQL search. The process is then repeated until the desired number of sky positions is attained.

Detection and discrimination of colour, a comparison of physiological and psychophysical data

NASA Astrophysics Data System (ADS)

Valberg, A.; Lee, B. B.

1989-01-01

Whereas the physiological basis of colorimetry (colour matches) is well understood in terms of the trireceptor theory of colour vision, colour discrimination and scaling still lack a comparable foundation. We present here experimental data that demonstrate how sensitivity and responsiveness of different types of cone-opponent and non-opponent cells of the macaque monkey correlate with human threshold sensitivity on the one hand, and how they in combination can be used to construct a suprathreshold equidistant colour space. Psychophysical thresholds correlate well with the threshold envelope of the most sensitive cells when stimuli are projected upon a steady white background. Detection thresholds for stimuli of differing wavelength and purity (saturation) generally indicate a transition from a phasic non-opponent system to a tonic opponent system of on-centre cells as purity increases. Detection and chromatic discrimination thresholds coincide only for long and short wavelengths of high purity, whereas they differ for mid-spectral lights. Different cell types may thus support detection and discrimination with different stimuli. With chromatic scaling of surface colours on the other hand, when stimuli are darker than an adaptation field still other cell types are needed. We demonstrate that it is possible, from a combination of on- and off-opponent cells, to reconstruct a uniform colour space, using summed outputs of cells with the same cone combination and vector addition for cells with different combinations. Different hues are represented by opponent cells with inputs from different cone types, the hue percept being related to the ratio of the activities of these cell systems.

Attention-deficit hyperactivity disorder and anxiety disorders as precursors of bipolar disorder onset in adulthood.

PubMed

Meier, Sandra M; Pavlova, Barbara; Dalsgaard, Søren; Nordentoft, Merete; Mors, Ole; Mortensen, Preben B; Uher, Rudolf

2018-06-21

Attention-deficit hyperactivity disorder (ADHD) and anxiety disorders have been proposed as precursors of bipolar disorder, but their joint and relative roles in the development of bipolar disorder are unknown.AimsTo test the prospective relationship of ADHD and anxiety with onset of bipolar disorder. We examined the relationship between ADHD, anxiety disorders and bipolar disorder in a birth cohort of 2 409 236 individuals born in Denmark between 1955 and 1991. Individuals were followed from their sixteenth birthday or from January 1995 to their first clinical contact for bipolar disorder or until December 2012. We calculated incidence rates per 10 000 person-years and tested the effects of prior diagnoses on the risk of bipolar disorder in survival models. Over 37 394 865 person-years follow-up, 9250 onsets of bipolar disorder occurred. The incidence rate of bipolar disorder was 2.17 (95% CI 2.12-2.19) in individuals with no prior diagnosis of ADHD or anxiety, 23.86 (95% CI 19.98-27.75) in individuals with a prior diagnosis of ADHD only, 26.05 (95% CI 24.47-27.62) in individuals with a prior diagnosis of anxiety only and 66.16 (95% CI 44.83-87.47) in those with prior diagnoses of both ADHD and anxiety. The combination of ADHD and anxiety increased the risk of bipolar disorder 30-fold (95% CI 21.66-41.40) compared with those with no prior ADHD or anxiety. Early manifestations of both internalising and externalising psychopathology indicate liability to bipolar disorder. The combination of ADHD and anxiety is associated with a very high risk of bipolar disorder.Declaration of interestNone.

Elevated left mid-frontal cortical activity prospectively predicts conversion to bipolar I disorder

PubMed Central

Nusslock, Robin; Harmon-Jones, Eddie; Alloy, Lauren B.; Urosevic, Snezana; Goldstein, Kim; Abramson, Lyn Y.

2013-01-01

Bipolar disorder is characterized by a hypersensitivity to reward-relevant cues and a propensity to experience an excessive increase in approach-related affect, which may be reflected in hypo/manic symptoms. The present study examined the relationship between relative left-frontal electroencephalographic (EEG) activity, a proposed neurophysiological index of approach-system sensitivity and approach/reward-related affect, and bipolar course and state-related variables. Fifty-eight individuals with cyclothymia or bipolar II disorder and 59 healthy control participants with no affective psychopathology completed resting EEG recordings. Alpha power was obtained and asymmetry indices computed for homologous electrodes. Bipolar spectrum participants were classified as being in a major/minor depressive episode, a hypomanic episode, or a euthymic/remitted state at EEG recording. Participants were then followed prospectively for an average 4.7 year follow-up period with diagnostic interview assessments every four-months. Sixteen bipolar spectrum participants converted to bipolar I disorder during follow-up. Consistent with hypotheses, elevated relative left-frontal EEG activity at baseline 1) prospectively predicted a greater likelihood of converting from cyclothymia or bipolar II disorder to bipolar I disorder over the 4.7 year follow-up period, 2) was associated with an earlier age-of-onset of first bipolar spectrum episode, and 3) was significantly elevated in bipolar spectrum individuals in a hypomanic episode at EEG recording. This is the first study to identify a neurophysiological marker that prospectively predicts conversion to bipolar I disorder. The fact that unipolar depression is characterized by decreased relative left-frontal EEG activity suggests that unipolar depression and vulnerability to hypo/mania may be characterized by different profiles of frontal EEG asymmetry. PMID:22775582

Impact of a cis-associated gene expression SNP on chromosome 20q11.22 on bipolar disorder susceptibility, hippocampal structure and cognitive performance.

PubMed

Li, Ming; Luo, Xiong-jian; Landén, Mikael; Bergen, Sarah E; Hultman, Christina M; Li, Xiao; Zhang, Wen; Yao, Yong-Gang; Zhang, Chen; Liu, Jiewei; Mattheisen, Manuel; Cichon, Sven; Mühleisen, Thomas W; Degenhardt, Franziska A; Nöthen, Markus M; Schulze, Thomas G; Grigoroiu-Serbanescu, Maria; Li, Hao; Fuller, Chris K; Chen, Chunhui; Dong, Qi; Chen, Chuansheng; Jamain, Stéphane; Leboyer, Marion; Bellivier, Frank; Etain, Bruno; Kahn, Jean-Pierre; Henry, Chantal; Preisig, Martin; Kutalik, Zoltán; Castelao, Enrique; Wright, Adam; Mitchell, Philip B; Fullerton, Janice M; Schofield, Peter R; Montgomery, Grant W; Medland, Sarah E; Gordon, Scott D; Martin, Nicholas G; Rietschel, Marcella; Liu, Chunyu; Kleinman, Joel E; Hyde, Thomas M; Weinberger, Daniel R; Su, Bing

2016-02-01

Bipolar disorder is a highly heritable polygenic disorder. Recent enrichment analyses suggest that there may be true risk variants for bipolar disorder in the expression quantitative trait loci (eQTL) in the brain. We sought to assess the impact of eQTL variants on bipolar disorder risk by combining data from both bipolar disorder genome-wide association studies (GWAS) and brain eQTL. To detect single nucleotide polymorphisms (SNPs) that influence expression levels of genes associated with bipolar disorder, we jointly analysed data from a bipolar disorder GWAS (7481 cases and 9250 controls) and a genome-wide brain (cortical) eQTL (193 healthy controls) using a Bayesian statistical method, with independent follow-up replications. The identified risk SNP was then further tested for association with hippocampal volume (n = 5775) and cognitive performance (n = 342) among healthy individuals. Integrative analysis revealed a significant association between a brain eQTL rs6088662 on chromosome 20q11.22 and bipolar disorder (log Bayes factor = 5.48; bipolar disorder P = 5.85 × 10(-5)). Follow-up studies across multiple independent samples confirmed the association of the risk SNP (rs6088662) with gene expression and bipolar disorder susceptibility (P = 3.54 × 10(-8)). Further exploratory analysis revealed that rs6088662 is also associated with hippocampal volume and cognitive performance in healthy individuals. Our findings suggest that 20q11.22 is likely a risk region for bipolar disorder; they also highlight the informative value of integrating functional annotation of genetic variants for gene expression in advancing our understanding of the biological basis underlying complex disorders, such as bipolar disorder. © The Royal College of Psychiatrists 2016.

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

PubMed Central

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. PMID:24030475

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

PubMed

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.

N-acetyl Aspartate Levels in Adolescents With Bipolar and/or Cannabis Use Disorders

PubMed Central

Bitter, Samantha M.; Weber, Wade A.; Chu, Wen-Jang; Adler, Caleb M.; Eliassen, James C.; Strakowski, Stephen M.; DelBello, Melissa P.

2014-01-01

Objective Bipolar and cannabis use disorders commonly co-occur during adolescence, and neurochemical studies may help clarify the pathophysiology underlying this co-occurrence. This study compared metabolite concentrations in the left ventral lateral prefrontal cortex among: adolescents with bipolar disorder (bipolar group; n=14), adolescents with a cannabis use disorder (cannabis use group, n=13), adolescents with cannabis use and bipolar disorders (bipolar and cannabis group, n=25), and healthy adolescents (healthy controls, n=15). We hypothesized that adolescents with bipolar disorder (with or without cannabis use disorder) would have decreased N-acetyl aspartate levels in the ventral lateral prefrontal cortex compared to the other groups, and that the bipolar and cannabis group would have the lowest N-acetyl aspartate levels of all groups. Methods N-acetyl aspartate concentrations in the left ventral lateral prefrontal cortex were obtained using Proton Magnetic Resonance Spectroscopy. Results Adolescents with bipolar disorder showed significantly lower left ventral lateral prefrontal cortex N-acetyl aspartate levels, but post-hoc analyses indicated that this was primarily due to increased N-acetyl aspartate levels in the cannabis group. The cannabis use disorder group had significantly higher N-acetyl aspartate levels compared to the bipolar disorder and the bipolar and cannabis groups (p=0.0002 and p=0.0002, respectively). Pearson correlations revealed a significant positive correlation between amount of cannabis used and N-acetyl aspartate concentrations. Conclusions Adolescents with cannabis use disorder showed higher levels of N-acetyl aspartate concentrations that were significantly positively associated with the amount of cannabis used; however, this finding was not present in adolescents with comorbid bipolar disorder. PMID:24729763

Olfactocentric paralimbic cortex morphology in adolescents with bipolar disorder

PubMed Central

Wang, Fei; Kalmar, Jessica H.; Womer, Fay Y.; Edmiston, Erin E.; Chepenik, Lara G.; Chen, Rachel; Spencer, Linda

2011-01-01

The olfactocentric paralimbic cortex plays a critical role in the regulation of emotional and neurovegetative functions that are disrupted in core features of bipolar disorder. Adolescence is thought to be a critical period in both the maturation of the olfactocentric paralimbic cortex and in the emergence of bipolar disorder pathology. Together, these factors implicate a central role for the olfactocentric paralimbic cortex in the development of bipolar disorder and suggest that abnormalities in this cortex may be expressed by adolescence in the disorder. We tested the hypothesis that differences in olfactocentric paralimbic cortex structure are a morphological feature in adolescents with bipolar disorder. Subjects included 118 adolescents (41 with bipolar disorder and 77 healthy controls). Cortical grey matter volume differences between adolescents with and without bipolar disorder were assessed with voxel-based morphometry analyses of high-resolution structural magnetic resonance imaging scans. Compared with healthy comparison adolescents, adolescents with bipolar disorder demonstrated significant volume decreases in olfactocentric paralimbic regions, including orbitofrontal, insular and temporopolar cortices. Findings in these regions survived small volume correction (P < 0.05, corrected). Volume decreases in adolescents with bipolar disorder were also noted in inferior prefrontal and superior temporal gyri and cerebellum. The findings suggest that abnormalities in the morphology of the olfactocentric paralimbic cortex may contribute to the bipolar disorder phenotype that emerges in adolescence. The morphological development of the olfactocentric paralimbic cortex has received little study. The importance of these cortices in emotional and social development, and support for a central role for these cortices in the development of bipolar disorder, suggest that study of the development of these cortices in health and in bipolar disorder is critically needed. PMID:21666263

Olfactocentric paralimbic cortex morphology in adolescents with bipolar disorder.

PubMed

Wang, Fei; Kalmar, Jessica H; Womer, Fay Y; Edmiston, Erin E; Chepenik, Lara G; Chen, Rachel; Spencer, Linda; Blumberg, Hilary P

2011-07-01

The olfactocentric paralimbic cortex plays a critical role in the regulation of emotional and neurovegetative functions that are disrupted in core features of bipolar disorder. Adolescence is thought to be a critical period in both the maturation of the olfactocentric paralimbic cortex and in the emergence of bipolar disorder pathology. Together, these factors implicate a central role for the olfactocentric paralimbic cortex in the development of bipolar disorder and suggest that abnormalities in this cortex may be expressed by adolescence in the disorder. We tested the hypothesis that differences in olfactocentric paralimbic cortex structure are a morphological feature in adolescents with bipolar disorder. Subjects included 118 adolescents (41 with bipolar disorder and 77 healthy controls). Cortical grey matter volume differences between adolescents with and without bipolar disorder were assessed with voxel-based morphometry analyses of high-resolution structural magnetic resonance imaging scans. Compared with healthy comparison adolescents, adolescents with bipolar disorder demonstrated significant volume decreases in olfactocentric paralimbic regions, including orbitofrontal, insular and temporopolar cortices. Findings in these regions survived small volume correction (P < 0.05, corrected). Volume decreases in adolescents with bipolar disorder were also noted in inferior prefrontal and superior temporal gyri and cerebellum. The findings suggest that abnormalities in the morphology of the olfactocentric paralimbic cortex may contribute to the bipolar disorder phenotype that emerges in adolescence. The morphological development of the olfactocentric paralimbic cortex has received little study. The importance of these cortices in emotional and social development, and support for a central role for these cortices in the development of bipolar disorder, suggest that study of the development of these cortices in health and in bipolar disorder is critically needed.

Computer modeling of electrical and thermal performance during bipolar pulsed radiofrequency for pain relief.

PubMed

Pérez, Juan J; Pérez-Cajaraville, Juan J; Muñoz, Víctor; Berjano, Enrique

2014-07-01

Pulsed RF (PRF) is a nonablative technique for treating neuropathic pain. Bipolar PRF application is currently aimed at creating a "strip lesion" to connect the electrode tips; however, the electrical and thermal performance during bipolar PRF is currently unknown. The objective of this paper was to study the temperature and electric field distributions during bipolar PRF. The authors developed computer models to study temperature and electric field distributions during bipolar PRF and to assess the possible ablative thermal effect caused by the accumulated temperature spikes, along with any possible electroporation effects caused by the electrical field. The authors also modeled the bipolar ablative mode, known as bipolar Continuous Radiofrequency (CRF), in order to compare both techniques. There were important differences between CRF and PRF in terms of electrical and thermal performance. In bipolar CRF: (1) the initial temperature of the tissue impacts on temperature progress and hence on the thermal lesion dimension; and (2) at 37 °C, 6-min of bipolar CRF creates a strip thermal lesion between the electrodes when these are separated by a distance of up to 20 mm. In bipolar PRF: (1) an interelectrode distance shorter than 5 mm produces thermal damage (i.e., ablative effect) in the intervening tissue after 6 min of bipolar RF; and (2) the possible electroporation effect (electric fields higher than 150 kV m(-1)) would be exclusively circumscribed to a very small zone of tissue around the electrode tip. The results suggest that (1) the clinical parameters considered to be suitable for bipolar CRF should not necessarily be considered valid for bipolar PRF, and vice versa; and (2) the ablative effect of the CRF mode is mainly due to its much greater level of delivered energy than is the case in PRF, and therefore at same applied energy levels, CRF, and PRF are expected to result in same outcomes in terms of thermal damage zone dimension.

Bipolarization and Poleward Flux Correlate during Xenopus Extract Spindle AssemblyV⃞

PubMed Central

Mitchison, T.J.; Maddox, P.; Groen, A.; Cameron, L.; Perlman, Z.; Ohi, R.; Desai, A.; Salmon, E.D.; Kapoor, T.M.

2004-01-01

We investigated the mechanism by which meiotic spindles become bipolar and the correlation between bipolarity and poleward flux, using Xenopus egg extracts. By speckle microscopy and computational alignment, we find that monopolar sperm asters do not show evidence for flux, partially contradicting previous work. We account for the discrepancy by describing spontaneous bipolarization of sperm asters that was missed previously. During spontaneous bipolarization, onset of flux correlated with onset of bipolarity, implying that antiparallel microtubule organization may be required for flux. Using a probe for TPX2 in addition to tubulin, we describe two pathways that lead to spontaneous bipolarization, new pole assembly near chromatin, and pole splitting. By inhibiting the Ran pathway with excess importin-alpha, we establish a role for chromatin-derived, antiparallel overlap bundles in generating the sliding force for flux, and we examine these bundles by electron microscopy. Our results highlight the importance of two processes, chromatin-initiated microtubule nucleation, and sliding forces generated between antiparallel microtubules, in self-organization of spindle bipolarity and poleward flux. PMID:15385629

Carbon composite bipolar plate for high-temperature proton exchange membrane fuel cells (HT-PEMFCs)

NASA Astrophysics Data System (ADS)

Lee, Dongyoung; Lee, Dai Gil

2016-09-01

A carbon/epoxy composite bipolar plate is an ideal substitute for the brittle graphite bipolar plate for lightweight proton exchange membrane fuel cells (PEMFCs) because of its high specific strength and stiffness. However, conventional carbon/epoxy composite bipolar plates are not applicable for high-temperature PEMFCs (HT-PEMFCs) because these systems are operated at higher temperatures than the glass transition temperatures of conventional epoxies. Therefore, in this study, a cyanate ester-modified epoxy is adopted for the development of a carbon composite bipolar plate for HT-PEMFCs. The composite bipolar plate with exposed surface carbon fibers is produced without any surface treatments or coatings to increase the productivity and is integrated with a silicone gasket to reduce the assembly cost. The developed carbon composite bipolar plate exhibits not only superior electrical properties but also high thermo-mechanical properties. In addition, a unit cell test is performed, and the results are compared with those of the conventional graphite bipolar plate.

Cross-national prevalence and cultural correlates of bipolar I disorder.

PubMed

Johnson, Kaja R; Johnson, Sheri L

2014-07-01

Bipolar disorder has been consistently related to heightened sensitivity to reward. Greater reward sensitivity predicts the onset of disorder, a more severe course, and conversion from milder to severe forms. No studies consider whether cultural factors related to reward sensitivity influence the course of bipolar disorder. This study examines the relationship of reward-relevant cultural values to global prevalence rates of bipolar I disorder. Lifetime prevalence of bipolar I disorder for 17 countries was drawn from epidemiological studies that used structured diagnostic interviews of large community samples. Bivariate correlations were used to assess the relationship of bipolar disorder prevalence with national scores on four reward-relevant cultural dimensions (Power Distance, Individualism, Long-Term Orientation, and Performance Orientation). The prevalence of bipolar I disorder was correlated in the predicted manner with Power Distance and Individualism, and with Long-Term Orientation and Performance Orientation after outliers were removed. Findings provide evidence for a cultural model of reward sensitivity in bipolar disorder.

New insights into the endophenotypic status of cognition in bipolar disorder: genetic modelling study of twins and siblings.

PubMed

Georgiades, Anna; Rijsdijk, Fruhling; Kane, Fergus; Rebollo-Mesa, Irene; Kalidindi, Sridevi; Schulze, Katja K; Stahl, Daniel; Walshe, Muriel; Sahakian, Barbara J; McDonald, Colm; Hall, Mei-Hua; Murray, Robin M; Kravariti, Eugenia

2016-06-01

Twin studies have lacked statistical power to apply advanced genetic modelling techniques to the search for cognitive endophenotypes for bipolar disorder. To quantify the shared genetic variability between bipolar disorder and cognitive measures. Structural equation modelling was performed on cognitive data collected from 331 twins/siblings of varying genetic relatedness, disease status and concordance for bipolar disorder. Using a parsimonious AE model, verbal episodic and spatial working memory showed statistically significant genetic correlations with bipolar disorder (rg = |0.23|-|0.27|), which lost statistical significance after covarying for affective symptoms. Using an ACE model, IQ and visual-spatial learning showed statistically significant genetic correlations with bipolar disorder (rg = |0.51|-|1.00|), which remained significant after covarying for affective symptoms. Verbal episodic and spatial working memory capture a modest fraction of the bipolar diathesis. IQ and visual-spatial learning may tap into genetic substrates of non-affective symptomatology in bipolar disorder. © The Royal College of Psychiatrists 2016.

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

PubMed

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 bipolar and personality phenotypes. BPD may be most associated with decreased extraversion (less interaction with one's surroundings) because patients spend more time in depressive than manic states. Copyright © 2011. Published by Elsevier B.V.

Perturbational Profiling of Metabolites in Patient Fibroblasts Implicates α-Aminoadipate as a Potential Biomarker for Bipolar Disorder

PubMed Central

Huang, Joanne H.; Berkovitch, Shaunna S.; Iaconelli, Jonathan; Watmuff, Bradley; Park, Hyoungjun; Chattopadhyay, Shrikanta; McPhie, Donna; Öngür, Dost; Cohen, Bruce M.; Clish, Clary B.; Karmacharya, Rakesh

2016-01-01

Many studies suggest the presence of aberrations in cellular metabolism in bipolar disorder. We studied the metabolome in bipolar disorder to gain insight into cellular pathways that may be dysregulated in bipolar disorder and to discover evidence of novel biomarkers. We measured polar and nonpolar metabolites in fibroblasts from subjects with bipolar I disorder and matched healthy control subjects, under normal conditions and with two physiologic perturbations: low-glucose media and exposure to the stress-mediating hormone dexamethasone. Metabolites that were significantly different between bipolar and control subjects showed distinct separation by principal components analysis methods. The most statistically significant findings were observed in the perturbation experiments. The metabolite with the lowest p value in both the low-glucose and dexamethasone experiments was α-aminoadipate, whose intracellular level was consistently lower in bipolar subjects. Our study implicates α-aminoadipate as a possible biomarker in bipolar disorder that manifests under cellular stress. This is an intriguing finding given the known role of α-aminoadipate in the modulation of kynurenic acid in the brain, especially as abnormal kynurenic acid levels have been implicated in bipolar disorder. PMID:27606323

Equilibrium relations and bipolar cognitive mapping for online analytical processing with applications in international relations and strategic decision support.

PubMed

Zhang, Wen-Ran

2003-01-01

Bipolar logic, bipolar sets, and equilibrium relations are proposed for bipolar cognitive mapping and visualization in online analytical processing (OLAP) and online analytical mining (OLAM). As cognitive models, cognitive maps (CMs) hold great potential for clustering and visualization. Due to the lack of a formal mathematical basis, however, CM-based OLAP and OLAM have not gained popularity. Compared with existing approaches, bipolar cognitive mapping has a number of advantages. First, bipolar CMs are formal logical models as well as cognitive models. Second, equilibrium relations (with polarized reflexivity, symmetry, and transitivity), as bipolar generalizations and fusions of equivalence relations, provide a theoretical basis for bipolar visualization and coordination. Third, an equilibrium relation or CM induces bipolar partitions that distinguish disjoint coalition subsets not involved in any conflict, disjoint coalition subsets involved in a conflict, disjoint conflict subsets, and disjoint harmony subsets. Finally, equilibrium energy analysis leads to harmony and stability measures for strategic decision and multiagent coordination. Thus, this work bridges a gap for CM-based clustering and visualization in OLAP and OLAM. Basic ideas are illustrated with example CMs in international relations.

Temperament and personality in bipolar II disorder.

PubMed

Fletcher, Kathryn; Parker, Gordon; Barrett, Melissa; Synnott, Howe; McCraw, Stacey

2012-02-01

There is limited research examining temperament and personality in bipolar II disorder. We sought to determine any over-represented temperament and personality features in bipolar II disorder compared to other affective groups. Scores on a self-report measure of temperament and personality were examined in a sample of 443 participants diagnosed with unipolar, bipolar I and bipolar II disorder. After controlling for age, gender, age of depression onset and current depression severity, those with bipolar II disorder were characterized by higher irritability, anxious worrying, self-criticism and interpersonal sensitivity scores, and with lower social avoidance scores compared to unipolar participants. No differences were found between bipolar sub-types on any temperament and personality sub-scales. Limitations included the lack of a control group, a relatively small sample of bipolar I participants, and with the cross-sectional design disallowing conclusions regarding premorbid personality traits as opposed to illness 'scarring' effects. Further research should seek to clarify whether certain temperament and personality styles are over-represented in bipolar II disorder. Any over-represented characteristics may assist with diagnostic differentiation from phenomenologically similar conditions and lead to more appropriate clinical management. Copyright © 2011 Elsevier B.V. All rights reserved.

Amygdala volume and verbal memory performance in schizophrenia and bipolar disorder.

PubMed

Killgore, William D S; Rosso, Isabelle M; Gruber, Staci A; Yurgelun-Todd, Deborah A

2009-03-01

To clarify the relationship between amygdala-hippocampal volume and cognitive performance in schizophrenia and bipolar disorder. Abnormalities of the amygdala-hippocampal complex and memory deficits have been reported in both schizophrenia and bipolar illness. We examined memory performance and its relationship to the volumes of the whole brain, lateral ventricles, hippocampus, and amygdala using morphometric magnetic resonance imaging in 19 patients with schizophrenia, 11 bipolar patients, and 20 healthy controls. Schizophrenia patients performed more poorly than bipolar patients and controls on indices of memory functioning, whereas patients with bipolar disorder showed milder impairments relative to controls. The schizophrenia group showed reduced total cerebral volume and enlarged ventricles relative to controls, but no group differences were found for amygdala or hippocampal volume. Left amygdala volume was predictive of memory performance in both groups, correlating positively with better immediate and delayed verbal memory for bipolar patients and negatively with immediate and delayed verbal recall for schizophrenia patients. Amygdala volume was unrelated to memory performance in healthy subjects. Schizophrenia and bipolar disorder both seem to be associated with anomalous and differential limbic volume-function relationships, such that the amygdala may facilitate hippocampal-dependent memory processes in bipolar disorder but impair these same processes in schizophrenia.

Initial depressive episodes affect the risk of suicide attempts in Korean patients with bipolar disorder.

PubMed

Ryu, Vin; Jon, Duk-In; Cho, Hyun Sang; Kim, Se Joo; Lee, Eun; Kim, Eun Joo; Seok, Jeong-Ho

2010-09-01

Suicide is a major concern for increasing mortality in bipolar patients, but risk factors for suicide in bipolar disorder remain complex, including Korean patients. Medical records of bipolar patients were retrospectively reviewed to detect significant clinical characteristics associated with suicide attempts. A total of 579 medical records were retrospectively reviewed. Bipolar patients were divided into two groups with the presence of a history of suicide attempts. We compared demographic characteristics and clinical features between the two groups using an analysis of covariance and chi-square tests. Finally, logistic regression was performed to evaluate significant risk factors associated with suicide attempts in bipolar disorder. The prevalence of suicide attempt was 13.1% in our patient group. The presence of a depressive first episode was significantly different between attempters and nonattempters. Logistic regression analysis revealed that depressive first episodes and bipolar II disorder were significantly associated with suicide attempts in those patients. Clinicians should consider the polarity of the first mood episode when evaluating suicide risk in bipolar patients. This study has some limitations as a retrospective study and further studies with a prospective design are needed to replicate and evaluate risk factors for suicide in patients with bipolar disorder.

Psychotherapy for Bipolar Disorder in Adults: A Review of the Evidence

PubMed Central

Swartz, Holly A.; Swanson, Joshua

2015-01-01

Although pharmacotherapy is the mainstay of treatment for bipolar disorder, medication offers only partial relief for patients. Treatment with pharmacologic interventions alone is associated with disappointingly low rates of remission, high rates of recurrence, residual symptoms, and psychosocial impairment. Bipolar-specific therapy is increasingly recommended as an essential component of illness management. This review summarizes the available data on psychotherapy for adults with bipolar disorder. We conducted a search of the literature for outcome studies published between 1995 and 2013 and identified 35 reports of 28 randomized controlled trials testing individual or group psychosocial interventions for adults with bipolar disorder. These reports include systematic trials investigating the efficacy and effectiveness of individual psychoeducation, group psychoeducation, individual cognitive-behavioral therapy, group cognitive-behavioral therapy, family therapy, interpersonal and social rhythm therapy, and integrated care management. The evidence demonstrates that bipolar disorder-specific psychotherapies, when added to medication for the treatment of bipolar disorder, consistently show advantages over medication alone on measures of symptom burden and risk of relapse. Whether delivered in a group or individual format, those who receive bipolar disorder-specific psychotherapy fare better than those who do not. Psychotherapeutic strategies common to most bipolar disorder-specific interventions are identified. PMID:26279641

Cone biopsy

MedlinePlus

... grade cone biopsy; High-grade cone biopsy; Carcinoma in situ-cone biopsy; CIS - cone biopsy; ASCUS - cone biopsy; ... marked dysplasia CIN III -- severe dysplasia to carcinoma in situ Abnormal results may also be due to cervical ...

Altered amygdala-prefrontal response to facial emotion in offspring of parents with bipolar disorder.

PubMed

Manelis, Anna; Ladouceur, Cecile D; Graur, Simona; Monk, Kelly; Bonar, Lisa K; Hickey, Mary Beth; Dwojak, Amanda C; Axelson, David; Goldstein, Benjamin I; Goldstein, Tina R; Bebko, Genna; Bertocci, Michele A; Hafeman, Danella M; Gill, Mary Kay; Birmaher, Boris; Phillips, Mary L

2015-09-01

This study aimed to identify neuroimaging measures associated with risk for, or protection against, bipolar disorder by comparing youth offspring of parents with bipolar disorder versus youth offspring of non-bipolar parents versus offspring of healthy parents in (i) the magnitude of activation within emotional face processing circuitry; and (ii) functional connectivity between this circuitry and frontal emotion regulation regions. The study was conducted at the University of Pittsburgh Medical Centre. Participants included 29 offspring of parents with bipolar disorder (mean age = 13.8 years; 14 females), 29 offspring of non-bipolar parents (mean age = 13.8 years; 12 females) and 23 healthy controls (mean age = 13.7 years; 11 females). Participants were scanned during implicit processing of emerging happy, sad, fearful and angry faces and shapes. The activation analyses revealed greater right amygdala activation to emotional faces versus shapes in offspring of parents with bipolar disorder and offspring of non-bipolar parents than healthy controls. Given that abnormally increased amygdala activation during emotion processing characterized offspring of both patient groups, and that abnormally increased amygdala activation has often been reported in individuals with already developed bipolar disorder and those with major depressive disorder, these neuroimaging findings may represent markers of increased risk for affective disorders in general. The analysis of psychophysiological interaction revealed that offspring of parents with bipolar disorder showed significantly more negative right amygdala-anterior cingulate cortex functional connectivity to emotional faces versus shapes, but significantly more positive right amygdala-left ventrolateral prefrontal cortex functional connectivity to happy faces (all P-values corrected for multiple tests) than offspring of non-bipolar parents and healthy controls. Taken together with findings of increased amygdala-ventrolateral prefrontal cortex functional connectivity, and decreased amygdala-anterior cingulate cortex functional connectivity previously shown in individuals with bipolar disorder, these connectivity patterns in offspring of parents with bipolar disorder may be risk markers for, rather than markers conferring protection against, bipolar disorder in youth. The patterns of activation and functional connectivity remained unchanged after removing medicated participants and those with current psychopathology from analyses. This is the first study to demonstrate that abnormal functional connectivity patterns within face emotion processing circuitry distinguish offspring of parents with bipolar disorder from those of non-bipolar parents and healthy controls. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Results from an online survey of patient and caregiver perspectives on unmet needs in the treatment of bipolar disorder.

PubMed

Masand, Prakash S; Tracy, Natasha

2014-01-01

To look at the manner in which patients and caregivers perceive the treatment of bipolar disorder compared with the evidence base for bipolar treatment. Between April 2013 and March 2014, 469 respondents took a 14-question online survey on demographics, medications taken, and perspectives on bipolar treatment and medications. Participants were recruited through social media outlets (Facebook and Twitter accounts) of Global Medical Education (New York, New York) and the blog Bipolar Burble, which has a primary audience of people with bipolar disorder. There were no exclusion criteria to participation, and both patients and health care professionals were encouraged to participate. Most respondents were taking ≥ 3 medications, and the greatest unmet need in treatment was for bipolar depression. In general, respondent perspectives on the effectiveness of individual medication treatments did not align with the available literature. Weight gain was the greatest side effect concern for both antipsychotics and mood stabilizers. Our survey demonstrates that there are still many unmet needs in the treatment of bipolar disorder. There is also a mismatch between the evidence base for treatments in bipolar disorder and patient perception of the relative efficacy of different medications. In order to achieve better outcomes, there is a need to provide patients and clinicians greater quality education with regard to the best evidence-based treatments for bipolar disorder.

Dorsal Anterior Cingulate Lactate and Glutathione Levels in Euthymic Bipolar I Disorder: 1H-MRS Study.

PubMed

Soeiro-de-Souza, Márcio Gerhardt; Pastorello, Bruno F; Leite, Cláudia da Costa; Henning, Anke; Moreno, Ricardo A; Garcia Otaduy, Maria Concepción

2016-08-01

Oxidative stress and mitochondrial dysfunction are 2 closely integrated processes implicated in the physiopathology of bipolar disorder. Advanced proton magnetic resonance spectroscopy techniques enable the measurement of levels of lactate, the main marker of mitochondrial dysfunction, and glutathione, the predominant brain antioxidant. The objective of this study was to measure brain lactate and glutathione levels in bipolar disorder and healthy controls. Eighty-eight individuals (50 bipolar disorder and 38 healthy controls) underwent 3T proton magnetic resonance spectroscopy in the dorsal anterior cingulate cortex (2x2x4.5cm(3)) using a 2-D JPRESS sequence. Lactate and glutathione were quantified using the ProFit software program. Bipolar disorder patients had higher dorsal anterior cingulate cortex lactate levels compared with controls. Glutathione levels did not differ between euthymic bipolar disorder and controls. There was a positive correlation between lactate and glutathione levels specific to bipolar disorder. No influence of medications on metabolites was observed. This is the most extensive magnetic resonance spectroscopy study of lactate and glutathione in bipolar disorder to date, and results indicated that euthymic bipolar disorder patients had higher levels of lactate, which might be an indication of altered mitochondrial function. Moreover, lactate levels correlated with glutathione levels, indicating a compensatory mechanism regardless of bipolar disorder diagnosis. © The Author 2016. Published by Oxford University Press on behalf of CINP.

Coping and personality in older patients with bipolar disorder.

PubMed

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 Neurobiology of Bipolar Disorder: An Integrated Approach

PubMed Central

2016-01-01

Bipolar disorder is a heterogeneous condition with myriad clinical manifestations and many comorbidities leading to severe disabilities in the biopsychosocial realm. The objective of this review article was to underline recent advances in knowledge regarding the neurobiology of bipolar disorder. A further aim was to draw attention to new therapeutic targets in the treatment of bipolar disorder. To accomplish these goals, an electronic search was undertaken of the PubMed database in August 2015 of literature published during the last 10 years on the pathophysiology of bipolar disorder. A wide-ranging evaluation of the existing work was done with search terms such as "mood disorders and biology," "bipolar disorder and HPA axis," "bipolar disorder and cytokines," "mood disorders and circadian rhythm," "bipolar disorder and oxidative stress," etc. This endeavor showed that bipolar disorder is a diverse condition sharing neurobiological mechanisms with major depressive disorder and psychotic spectrum disorders. There is convincing evidence of crosstalk between different biological systems that act in a deleterious manner causing expression of the disease in genetically predisposed individuals. Inflammatory mediators act in concert with oxidative stress to dysregulate hormonal, metabolic, and circadian homeostasis in precipitating and perpetuating the illness. Stress, whether biologically or psychologically mediated, is responsible for the initiation and progression of the diathesis. Bipolar spectrum disorders have a strong genetic component; severe life stresses acting through various paths cause the illness phenotype. PMID:26865997

Epidemiology and burden of bipolar disorder in Africa: a systematic review of data from Africa.

PubMed

Esan, Oluyomi; Esan, Arinola

2016-01-01

Bipolar disorder impacts negatively on the patient, the family, as well as the society. It taxes the health care services due to a combination of the illness with associated medical and psychiatric comorbidities. In Africa, unfortunately, knowledge of the epidemiology and burden of bipolar disorder is based mainly on studies from the USA and Europe. In this systematic review of literature from Africa, we highlight the epidemiology and burden of bipolar disorder. A systematic review of publications from Africa relating to the epidemiology and burden of bipolar disorder was conducted. Data from community surveys conducted in Nigeria and Ethiopia indicated a lifetime prevalence estimate of 0.1 % to 1.83 for bipolar disorder. Missed diagnosis rate of bipolar disorder was up to 36.2 %. In one study, 8.1 % of the males and 5.4 % of the females reported a previous suicide attempt. A study showed that up to 60 % of patients with bipolar disorder had at least one comorbidity. There were no reports on all-cause mortality and cost of illness. Bipolar disorder is a major mental health problem in Africa. Scientific findings on bipolar disorder from Africa are consistent with the existing literature from other parts of the world. There still exists a dearth of high quality studies addressing the epidemiological, clinical, social, and economic burden of the disorder.

Dorsal Anterior Cingulate Lactate and Glutathione Levels in Euthymic Bipolar I Disorder: 1H-MRS Study

PubMed Central

Pastorello, Bruno F.; Leite, Cláudia da Costa; Henning, Anke; Moreno, Ricardo A.; Garcia Otaduy, Maria Concepción

2016-01-01

Objective: Oxidative stress and mitochondrial dysfunction are 2 closely integrated processes implicated in the physiopathology of bipolar disorder. Advanced proton magnetic resonance spectroscopy techniques enable the measurement of levels of lactate, the main marker of mitochondrial dysfunction, and glutathione, the predominant brain antioxidant. The objective of this study was to measure brain lactate and glutathione levels in bipolar disorder and healthy controls. Methods: Eighty-eight individuals (50 bipolar disorder and 38 healthy controls) underwent 3T proton magnetic resonance spectroscopy in the dorsal anterior cingulate cortex (2x2x4.5cm3) using a 2-D JPRESS sequence. Lactate and glutathione were quantified using the ProFit software program. Results: Bipolar disorder patients had higher dorsal anterior cingulate cortex lactate levels compared with controls. Glutathione levels did not differ between euthymic bipolar disorder and controls. There was a positive correlation between lactate and glutathione levels specific to bipolar disorder. No influence of medications on metabolites was observed. Conclusion: This is the most extensive magnetic resonance spectroscopy study of lactate and glutathione in bipolar disorder to date, and results indicated that euthymic bipolar disorder patients had higher levels of lactate, which might be an indication of altered mitochondrial function. Moreover, lactate levels correlated with glutathione levels, indicating a compensatory mechanism regardless of bipolar disorder diagnosis. PMID:27207914

Risk factors for suicide in bipolar disorder: a systematic review.

PubMed

Costa, Lucas da Silva; Alencar, Átila Pereira; Nascimento Neto, Pedro Januário; dos Santos, Maria do Socorro Vieira; da Silva, Cláudio Gleidiston Lima; Pinheiro, Sally de França Lacerda; Silveira, Regiane Teixeira; Bianco, Bianca Alves Vieira; Pinheiro, Roberto Flávio Fontenelle; de Lima, Marcos Antonio Pereira; Reis, Alberto Olavo Advincula; Rolim Neto, Modesto Leite

2015-01-01

Bipolar disorder confers the highest risk of suicide among major psychological disorders. The risk factors associated with bipolar disorder and suicide exist and are relevant to clinicians and researchers. The aim of the present study was to conduct a systematic review of articles regarding the suicide risk factors in bipolar disorder. A systematic review of articles on suicide risk factors in bipolar disorder, published from January 1, 2010 to April 05, 2014, on SCOPUS and PUBMED databases was carried out. Search terms were "Suicide" (medical subject headings [MeSH]), "Risk factors" (MeSH), and "Bipolar" (keyword). Of the 220 retrieved studies, 42 met the eligibility criteria. Bipolar disorder is associated with an increased rate death by suicide which contributes to overall mortality rates. Studies covered a wide range of aspects regarding suicide risk factors in bipolar disorder, such as risk factors associated to Sociodemographic conditions, Biological characteristics, Drugs Relationships, Psychological Factors, Genetic Compound, Religious and Spirituals conditions. Recent scientific literature regarding the suicide risk factors in bipolar disorder converge to, directly or indirectly, highlight the negative impacts of risk factors to the affected population quality of life. This review demonstrated that Bipolar disorders commonly leads to other psychiatric disorders and co-morbidities involving risk of suicide. Thus the risk factors are relevant to have a better diagnosis and prognosis of BD cases involving risk of suicide. Copyright © 2014 Elsevier B.V. All rights reserved.

[Lithium and anticonvulsants in bipolar depression].

PubMed

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.

Spectral characteristics of light sources for S-cone stimulation.

PubMed

Schlegelmilch, F; Nolte, R; Schellhorn, K; Husar, P; Henning, G; Tornow, R P

2002-11-01

Electrophysiological investigations of the short-wavelength sensitive pathway of the human eye require the use of a suitable light source as a S-cone stimulator. Different light sources with their spectral distribution properties were investigated and compared with the ideal S-cone stimulator. First, the theoretical background of the calculation of relative cone energy absorption from the spectral distribution function of the light source is summarized. From the results of the calculation, the photometric properties of the ideal S-cone stimulator will be derived. The calculation procedure was applied to virtual light sources (computer generated spectral distribution functions with different medium wavelengths and spectrum widths) and to real light sources (blue and green light emitting diodes, blue phosphor of CRT-monitor, multimedia projector, LCD monitor and notebook display). The calculated relative cone absorbencies are compared to the conditions of an ideal S-cone stimulator. Monochromatic light sources with wavelengths of less than 456 nm are close to the conditions of an ideal S-cone stimulator. Spectrum widths up to 21 nm do not affect the S-cone activation significantly (S-cone activation change < 0.2%). Blue light emitting diodes with peak wavelength at 448 nm and spectrum bandwidth of 25 nm are very useful for S-cone stimulation (S-cone activation approximately 95%). A suitable display for S-cone stimulation is the Trinitron computer monitor (S-cone activation approximately 87%). The multimedia projector has a S-cone activation up to 91%, but their spectral distribution properties depends on the selected intensity. LCD monitor and notebook displays have a lower S-cone activation (< or = 74%). Carefully selecting the blue light source for S-cone stimulation can reduce the unwanted L-and M-cone activation down to 4% for M-cones and 1.5% for L-cones.

Family environment patterns in families with bipolar children.

PubMed

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 (p<0.001), expressiveness (p=0.005), active-recreational orientation (p<0.001), intellectual-cultural orientation (p=0.04) and higher levels of conflict (p<0.001) compared to parents with no bipolar children. Secondary analyses within the bipolar group revealed lower levels of organization (p=0.031) and cohesion (p=0.014) in families 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.

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

PubMed

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.

Trends in diagnosis of bipolar disorder: Have the boundaries changed?

PubMed

Sara, Grant E; Malhi, Gin S

2015-11-01

There are concerns that the diagnostic boundaries of bipolar disorder have expanded. This study seeks evidence of change in diagnostic practice at three boundaries: the 'lower' boundary with subclinical mood conditions, the 'lateral' boundary with other mental health conditions (psychotic, anxiety, substance and personality disorders) and the 'internal' boundary within affective disorders. Diagnoses recorded in health system administrative data collections were used as a measure of clinician diagnostic behaviour. We examined all diagnoses made by public (state operated) inpatient and community mental health services in New South Wales, Australia, from 2003 to 2014. A total of 31,746 people had at least one recorded diagnosis of bipolar disorder in the period. There was a significant upward trend in the age-standardised population rate of diagnosis of bipolar disorder. Bipolar disorders made up an increasing proportion of psychosis diagnoses. There was no increase in the rate of comorbid diagnosis of bipolar disorders with non-psychotic disorders or in the likelihood of diagnosis of bipolar disorder at first or subsequent episodes of depression. There were significant reductions in diagnoses of schizophrenia, particularly in younger people. There may be some increase in diagnoses of bipolar disorder in New South Wales public mental health services. However, some changes in diagnosis, particularly in younger adults, may reflect movement away from diagnoses of schizophrenia towards a range of other diagnoses, rather than specific movement towards bipolar disorder. Expansion of bipolar disorder may have been more marked in private practice settings and may have involved the poorly defined bipolar II subtype. © The Royal Australian and New Zealand College of Psychiatrists 2015.

Two years' outcome of acute mania in bipolar disorder: different effects of age and age of onset.

PubMed

Oostervink, Frits; Nolen, Willem A; Kok, Rob M

2015-02-01

Information about differences between younger and older patients with bipolar disorder and between older patients with early and late age of onset of illness during long-term treatment is scarce. This study aimed to investigate the differences in treatment and treatment outcome between older and younger manic bipolar patients and between early-onset bipolar (EOB) and late-onset bipolar (LOB) older patients. The European Mania in Bipolar Longitudinal Evaluation of Medication study was a 2-year prospective, observational study in 3459 bipolar patients on the treatment and outcome of patients with an acute manic or mixed episode. Patients were assessed at 6, 12, 18, and 24 months post-baseline. We calculated the number of patients with a remission, recovery, relapse, and recurrence and the mean time to achieve this. Older patients did not differ from younger bipolar patients in achieving remission and recovery or suffering a relapse and in the time to achieve this. However, more older patients recurred and in shorter time. Older patients used less atypical antipsychotics and more antidepressants and other concomitant psychiatric medication. Older EOB and LOB patients did not differ in treatment, but more older LOB patients tended to recover than older EOB patients. Older bipolar manic patients did not differ from younger bipolar patients in short-term treatment outcome (remission and recovery), but in the long term, this may be more difficult to maintain. Distinguishing age groups in bipolar study populations may be useful when considering treatment and treatment outcome and warrants further study. Copyright © 2014 John Wiley & Sons, Ltd.

Feed-back modulation of cone synapses by L-horizontal cells of turtle retina.

PubMed

Gerschenfeld, H M; Piccolino, M; Neyton, J

1980-12-01

Light stimulation of the periphery of the receptive field of turtle cones can evoke both transient and sustained increases of the cone Ca2+ conductance, which may become regenerative. Such increase in the cone Ca2+ conductance evoked by peripheral illumination results from the activation of a polysynaptic pathway involving a feed-back connexion from the L-horizontal cells (L-HC) to the cones. Thus the hyperpolarization of a L-HC by inward current injection can evoke a Ca2+ conductance increase in neighbouring cones. The cone Ca2+ channels thus activated are likely located at its synaptic endings and probably intervene in the cone transmitter release. Therefore the feed-back connexion between L-HC and cones by modifying the Ca2+ conductance of cones could actually modulate the transmitter release from cone synapses. Such feed-back modulation of cone synapses plays a role in the organization of the colour-coded responses of the chromaticity type-horizontal cells and probably of other second order neurones, post-synaptic to the cones. The mechanisms operating the feed-back connexion from L-HC to cones are discussed.

Number and Distribution of Mouse Retinal Cone Photoreceptors: Differences between an Albino (Swiss) and a Pigmented (C57/BL6) Strain

PubMed Central

Jiménez-López, Manuel; Alburquerque-Béjar, Juan J.; Nieto-López, Leticia; García-Ayuso, Diego; Villegas-Pérez, Maria P.; Vidal-Sanz, Manuel; Agudo-Barriuso, Marta

2014-01-01

We purpose here to analyze and compare the population and topography of cone photoreceptors in two mouse strains using automated routines, and to design a method of retinal sampling for their accurate manual quantification. In whole-mounted retinas from pigmented C57/BL6 and albino Swiss mice, the longwave-sensitive (L) and the shortwave-sensitive (S) opsins were immunodetected to analyze the population of each cone type. In another group of retinas both opsins were detected with the same fluorophore to quantify all cones. In a third set of retinas, L-opsin and Brn3a were immunodetected to determine whether L-opsin+cones and retinal ganglion cells (RGCs) have a parallel distribution. Cones and RGCs were automatically quantified and their topography illustrated with isodensity maps. Our results show that pigmented mice have a significantly higher number of total cones (all-cones) and of L-opsin+cones than albinos which, in turn, have a higher population of S-opsin+cones. In pigmented animals 40% of cones are dual (cones that express both opsins), 34% genuine-L (cones that only express the L-opsin), and 26% genuine-S (cones that only express the S-opsin). In albinos, 23% of cones are genuine-S and the proportion of dual cones increases to 76% at the expense of genuine-L cones. In both strains, L-opsin+cones are denser in the central than peripheral retina, and all-cones density increases dorso-ventrally. In pigmented animals S-opsin+cones are scarce in the dorsal retina and very numerous in the ventral retina, being densest in its nasal aspect. In albinos, S-opsin+cones are abundant in the dorsal retina, although their highest densities are also ventral. Based on the densities of each cone population, we propose a sampling method to manually quantify and infer their total population. In conclusion, these data provide the basis to study cone degeneration and its prevention in pathologic conditions. PMID:25029531

Effects of temperature distribution on boundary layer stability for a circular cone at Mach 10

NASA Astrophysics Data System (ADS)

Rigney, Jeffrey M.

A CFD analysis was conducted on a circular cone at 3 degrees angle of attack at Mach 10 using US3D and STABL 3D to determine the effect of wall temperature on the stability characteristics that lead to laminar-to-turbulent transition. Wall temperature distributions were manipulated while all other flow inputs and geometric qualities were held constant. Laminar-to-turbulent transition was analyzed for isothermal and adiabatic wall conditions, a simulated short-duration wind tunnel case, and several hot-nose temperature distributions. For this study, stability characteristics include maximum N-factor growth and the corresponding frequency range, disturbance spatial amplification rate and the corresponding modal frequency, and stability neutral point location. STABL 3D analysis indicates that temperature distributions typical of those in short-duration hypersonic wind tunnels do not result in any significant difference on the stability characteristics, as compared to an isothermal wall boundary condition. Hypothetical distributions of much greater temperatures at and past the nose tip do show a trend of dampening of second-mode disturbances, most notably on the leeward ray. The most pronounced differences existed between the isothermal and adiabatic cases.

Gene therapy for red-green colour blindness in adult primates

PubMed Central

Mancuso, Katherine; Hauswirth, William W.; Li, Qiuhong; Connor, Thomas B.; Kuchenbecker, James A.; Mauck, Matthew C.; Neitz, Jay; Neitz, Maureen

2009-01-01

Red-green colour blindness, which results from the absence of either the long- (L) or middle- (M) wavelength-sensitive visual photopigments, is the most common single locus genetic disorder. Here, the possibility of curing colour blindness using gene therapy was explored in experiments on adult monkeys that had been colour blind since birth. A third type of cone pigment was added to dichromatic retinas, providing the receptoral basis for trichromatic colour vision. This opened a new avenue to explore the requirements for establishing the neural circuits for a new dimension of colour sensation. Classic visual deprivation experiments1 have led to the expectation that neural connections established during development would not appropriately process an input that was not present from birth. Therefore, it was believed that treatment of congenital vision disorders would be ineffective unless administered to the very young. Here, however, addition of a third opsin in adult red-green colour-deficient primates was sufficient to produce trichromatic colour vision behaviour. Thus, trichromacy can arise from a single addition of a third cone class and it does not require an early developmental process. This provides a positive outlook for the potential of gene therapy to cure adult vision disorders. PMID:19759534

Gene therapy for red-green colour blindness in adult primates.

PubMed

Mancuso, Katherine; Hauswirth, William W; Li, Qiuhong; Connor, Thomas B; Kuchenbecker, James A; Mauck, Matthew C; Neitz, Jay; Neitz, Maureen

2009-10-08

Red-green colour blindness, which results from the absence of either the long- (L) or the middle- (M) wavelength-sensitive visual photopigments, is the most common single locus genetic disorder. Here we explore the possibility of curing colour blindness using gene therapy in experiments on adult monkeys that had been colour blind since birth. A third type of cone pigment was added to dichromatic retinas, providing the receptoral basis for trichromatic colour vision. This opened a new avenue to explore the requirements for establishing the neural circuits for a new dimension of colour sensation. Classic visual deprivation experiments have led to the expectation that neural connections established during development would not appropriately process an input that was not present from birth. Therefore, it was believed that the treatment of congenital vision disorders would be ineffective unless administered to the very young. However, here we show that the addition of a third opsin in adult red-green colour-deficient primates was sufficient to produce trichromatic colour vision behaviour. Thus, trichromacy can arise from a single addition of a third cone class and it does not require an early developmental process. This provides a positive outlook for the potential of gene therapy to cure adult vision disorders.

Imaging Spectrophotometry of the Jet/ISM Interaction in IC5063

NASA Technical Reports Server (NTRS)

Cecil, G.; Schuft, B.; Morse, J.; Bland-Hawthorn, J.

2004-01-01

IC5063 is a somewhat dusty z=0.0110 S0 galaxy with a Seyfert 2 nucleus. It has a triple radio source that spans 3 arcsec, mostly blueshifted H I absorption that spans 700 km/s, and ionization cones that extend for more than 2 arcmins. We obtained fully sampled [O III]\\lambda5007 grids at 0."9 and 70 km/s FWHM resolution using the Rutgers Fabry-Perot system on the Blanco 4m telescope. Complementary long-slit spectra using the RC spectrograph on the Blanco, and Taurus Tunable Filter spectral images in H\\alpha and [N II]\\lambda6583, were also obtained to assess gaseous ionization conditions. We present the results of our analysis, and correlate spectral structures to those visible in archival WFPC2 images. We find that, in the region near the radio triple, gaseous ionization and line velocity width is tightly correlated, in excellent quantitative agreement with the high-velocity shock regime in the diagnostic emission-line ratio diagrams of Dopita & Sutherland. We separate kinematically gas in normal disk rotation that is illuminated by the AGN in the ionization cones from that agitated mechanically by the jet, and assess the energy input from both processes.

Human-In-The-Loop Investigation of Interoperability Between Terminal Sequencing and Spacing, Automated Terminal Proximity Alert, and Wake-Separation Recategorization

NASA Technical Reports Server (NTRS)

Callantine, Todd J.; Bienert, Nancy; Borade, Abhay; Gabriel, Conrad; Gujral, Vimmy; Jobe, Kim; Martin, Lynne; Omar, Faisal; Prevot, Thomas; Mercer, Joey

2016-01-01

A human-in-the-loop simulation study addressed terminal-area controller-workstation interface variations for interoperability between three new capabilities being introduced by the FAA. The capabilities are Terminal Sequencing and Spacing (TSAS), Automated Terminal Proximity Alert (ATPA), and wake-separation recategorization, or 'RECAT.' TSAS provides controllers with Controller-Managed Spacing (CMS) tools, including slot markers, speed advisories, and early/late indications, together with runway assignments and sequence numbers. ATPA provides automatic monitor, warning, and alert cones to inform controllers about spacing between aircraft on approach. ATPA cones are sized according to RECAT, an improved method of specifying wake-separation standards. The objective of the study was to identify potential issues and provide recommendations for integrating TSAS with ATPA and RECAT. Participants controlled arrival traffic under seven different display configurations, then tested an 'exploratory' configuration developed with participant input. All the display conditions were workable and acceptable, but controllers strongly preferred having the CMS tools available on Feeder positions, and both CMS tools and ATPA available on Final positions. Controllers found the integrated systems favorable and liked being able to tailor configurations to individual preferences.

Maximum life spiral bevel reduction design

NASA Technical Reports Server (NTRS)

Savage, M.; Prasanna, M. G.; Coe, H. H.

1992-01-01

Optimization is applied to the design of a spiral bevel gear reduction for maximum life at a given size. A modified feasible directions search algorithm permits a wide variety of inequality constraints and exact design requirements to be met with low sensitivity to initial values. Gear tooth bending strength and minimum contact ratio under load are included in the active constraints. The optimal design of the spiral bevel gear reduction includes the selection of bearing and shaft proportions in addition to gear mesh parameters. System life is maximized subject to a fixed back-cone distance of the spiral bevel gear set for a specified speed ratio, shaft angle, input torque, and power. Significant parameters in the design are: the spiral angle, the pressure angle, the numbers of teeth on the pinion and gear, and the location and size of the four support bearings. Interpolated polynomials expand the discrete bearing properties and proportions into continuous variables for gradient optimization. After finding the continuous optimum, a designer can analyze near optimal designs for comparison and selection. Design examples show the influence of the bearing lives on the gear parameters in the optimal configurations. For a fixed back-cone distance, optimal designs with larger shaft angles have larger service lives.

Design of a Soil Cutting Resistance Sensor for Application in Site-Specific Tillage

PubMed Central

Agüera, Juan; Carballido, Jacob; Gil, Jesús; Gliever, Chris J.; Perez-Ruiz, Manuel

2013-01-01

One objective of precision agriculture is to provide accurate information about soil and crop properties to optimize the management of agricultural inputs to meet site-specific needs. This paper describes the development of a sensor equipped with RTK-GPS technology that continuously and efficiently measures soil cutting resistance at various depths while traversing the field. Laboratory and preliminary field tests verified the accuracy of this prototype soil strength sensor. The data obtained using a hand-operated soil cone penetrometer was used to evaluate this field soil compaction depth profile sensor. To date, this sensor has only been tested in one field under one gravimetric water content condition. This field test revealed that the relationships between the soil strength profile sensor (SSPS) cutting force and soil cone index values are assumed to be quadratic for the various depths considered: 0–10, 10–20 and 20–30 cm (r2 = 0.58, 0.45 and 0.54, respectively). Soil resistance contour maps illustrated its practical value. The developed sensor provides accurate, timely and affordable information on soil properties to optimize resources and improve agricultural economy. PMID:23666127

Research on axisymmetric aspheric surface numerical design and manufacturing technology

NASA Astrophysics Data System (ADS)

Wang, Zhen-zhong; Guo, Yin-biao; Lin, Zheng

2006-02-01

The key technology for aspheric machining offers exact machining path and machining aspheric lens with high accuracy and efficiency, in spite of the development of traditional manual manufacturing into nowadays numerical control (NC) machining. This paper presents a mathematical model between virtual cone and aspheric surface equations, and discusses the technology of uniform wear of grinding wheel and error compensation in aspheric machining. Finally, a software system for high precision aspheric surface manufacturing is designed and realized, based on the mentioned above. This software system can work out grinding wheel path according to input parameters and generate machining NC programs of aspheric surfaces.

User's manual for CNVUFAC, the general dynamics heat-transfer radiation view factor program

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

Wong, R. L.

CNVUFAC, the General Dynamics heat-transfer radiation veiw factor program, has been adapted for use on the LLL CDC 7600 computer system. The input and output have been modified, and a node incrementing logic was included to make the code compatible with the TRUMP thermal analyzer and related codes. The program performs the multiple integration necessary to evaluate the geometric black-body radiaton node to node view factors. Card image output that contains node number and view factor information is generated for input into the related program GRAY. Program GRAY is then used to include the effects of gray-body emissivities and multiplemore » reflections, generating the effective gray-body view factors usable in TRUMP. CNVUFAC uses an elemental area summation scheme to evaluate the multiple integrals. The program permits shadowing and self-shadowing. The basic configuration shapes that can be considered are cylinders, cones, spheres, ellipsoids, flat plates, disks, toroids, and polynomials of revolution. Portions of these shapes can also be considered.« less

Manual for obscuration code with space station applications

NASA Technical Reports Server (NTRS)

Marhefka, R. J.; Takacs, L.

1986-01-01

The Obscuration Code, referred to as SHADOW, is a user-oriented computer code to determine the case shadow of an antenna in a complex environment onto the far zone sphere. The surrounding structure can be composed of multiple composite cone frustums and multiply sided flat plates. These structural pieces are ideal for modeling space station configurations. The means of describing the geometry input is compatible with the NEC-BASIC Scattering Code. In addition, an interactive mode of operation has been provided for DEC VAX computers. The first part of this document is a user's manual designed to give a description of the method used to obtain the shadow map, to provide an overall view of the operation of the computer code, to instruct a user in how to model structures, and to give examples of inputs and outputs. The second part is a code manual that details how to set up the interactive and non-interactive modes of the code and provides a listing and brief description of each of the subroutines.

Development of Refractive Errors-What Can We Learn From Inherited Retinal Dystrophies?

PubMed

Hendriks, Michelle; Verhoeven, Virginie J M; Buitendijk, Gabriëlle H S; Polling, Jan Roelof; Meester-Smoor, Magda A; Hofman, Albert; Kamermans, Maarten; Ingeborgh van den Born, L; Klaver, Caroline C W

2017-10-01

It is unknown which retinal cells are involved in the retina-to-sclera signaling cascade causing myopia. As inherited retinal dystrophies (IRD) are characterized by dysfunction of a single retinal cell type and have a high risk of refractive errors, a study investigating the affected cell type, causal gene, and refractive error in IRDs may provide insight herein. Case-control study. Study Population: Total of 302 patients with IRD from 2 ophthalmogenetic centers in the Netherlands. Reference Population: Population-based Rotterdam Study-III and Erasmus Rucphen Family Study (N = 5550). Distributions and mean spherical equivalent (SE) were calculated for main affected cell type and causal gene; and risks of myopia and hyperopia were evaluated using logistic regression. Bipolar cell-related dystrophies were associated with the highest risk of SE high myopia 239.7; odds ratio (OR) mild hyperopia 263.2, both P < .0001; SE -6.86 diopters (D) (standard deviation [SD] 6.38), followed by cone-dominated dystrophies (OR high myopia 19.5, P < .0001; OR high hyperopia 10.7, P = .033; SE -3.10 D [SD 4.49]); rod dominated dystrophies (OR high myopia 10.1, P < .0001; OR high hyperopia 9.7, P = .001; SE -2.27 D [SD 4.65]), and retinal pigment epithelium (RPE)-related dystrophies (OR low myopia 2.7; P = .001; OR high hyperopia 5.8; P = .025; SE -0.10 D [SD 3.09]). Mutations in RPGR (SE -7.63 D [SD 3.31]) and CACNA1F (SE -5.33 D [SD 3.10]) coincided with the highest degree of myopia and in CABP4 (SE 4.81 D [SD 0.35]) with the highest degree of hyperopia. Refractive errors, in particular myopia, are common in IRD. The bipolar synapse and the inner and outer segments of the photoreceptor may serve as critical sites for myopia development. Copyright © 2017 Elsevier Inc. All rights reserved.

Proinsulin slows retinal degeneration and vision loss in the P23H rat model of retinitis pigmentosa.

PubMed

Fernández-Sánchez, Laura; Lax, Pedro; Isiegas, Carolina; Ayuso, Eduard; Ruiz, José M; de la Villa, Pedro; Bosch, Fatima; de la Rosa, Enrique J; Cuenca, Nicolás

2012-12-01

Proinsulin has been characterized as a neuroprotective molecule. In this work we assess the therapeutic potential of proinsulin on photoreceptor degeneration, synaptic connectivity, and functional activity of the retina in the transgenic P23H rat, an animal model of autosomal dominant retinitis pigmentosa (RP). P23H homozygous rats received an intramuscular injection of an adeno-associated viral vector serotype 1 (AAV1) expressing human proinsulin (hPi+) or AAV1-null vector (hPi-) at P20. Levels of hPi in serum were determined by enzyme-linked immunosorbent assay (ELISA), and visual function was evaluated by electroretinographic (ERG) recording at P30, P60, P90, and P120. Preservation of retinal structure was assessed by immunohistochemistry at P120. Human proinsulin was detected in serum from rats injected with hPi+ at all times tested, with average hPi levels ranging from 1.1 nM (P30) to 1.4 nM (P120). ERG recordings showed an amelioration of vision loss in hPi+ animals. The scotopic b-waves were significantly higher in hPi+ animals than in control rats at P90 and P120. This attenuation of visual deterioration correlated with a delay in photoreceptor degeneration and the preservation of retinal cytoarchitecture. hPi+ animals had 48.7% more photoreceptors than control animals. Presynaptic and postsynaptic elements, as well as the synaptic contacts between photoreceptors and bipolar or horizontal cells, were preserved in hPi+ P23H rats. Furthermore, in hPi+ rat retinas the number of rod bipolar cell bodies was greater than in control rats. Our data demonstrate that hPi expression preserves cone and rod structure and function, together with their contacts with postsynaptic neurons, in the P23H rat. These data strongly support the further development of proinsulin-based therapy to counteract retinitis pigmentosa.

2017 Bipolar Plate Workshop Summary Report

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

Kopasz, John P.; Benjamin, Thomas G.; Schenck, Deanna

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 themore » bipolar plate.« less

[Pediatric bipolar disorder - case report of a bipolar patient with disease onset in childhood and adolescence: implications for diagnosis and therapy].

PubMed

Lackner, N; Birner, A; Bengesser, S A; Reininghaus, B; Kapfhammer, H P; Reininghaus, E

2014-11-01

In recent years, intense controversies have evolved about the existence and exact diagnostic criteria of pediatric bipolar affective disorder. The present study aims to discuss pediatric bipolar affective disorder based on the current literature focussing on the diagnostic prospects. Based on a case study, a process of bipolar disorder developed in childhood is depicted exemplarily. Because of the high comorbidity and overlapping symptoms of paediatric bipolar affective disorder and other psychiatric disorders, the major impact of the differential diagnosis has to be stressed. An early diagnosis and the treatment possibilities are discussed. © Georg Thieme Verlag KG Stuttgart · New York.

Clinical status of comorbid bipolar disorder and borderline personality disorder.

PubMed

Parker, Gordon; Bayes, Adam; McClure, Georgia; Del Moral, Yolanda Romàn Ruiz; Stevenson, Janine

2016-09-01

The status and differentiation of comorbid borderline personality disorder and bipolar disorder is worthy of clarification. To determine whether comorbid borderline personality disorder and bipolar disorder are interdependent or independent conditions. We interviewed patients diagnosed with either a borderline personality disorder and/or a bipolar condition. Analyses of participants grouped by DSM diagnoses established that those with comorbid conditions scored similarly to those with a borderline personality disorder alone on all key variables (i.e. gender, severity of borderline personality scores, developmental stressors, illness correlates, self-injurious behaviour rates) and differed from those with a bipolar disorder alone on nearly all non-bipolar item variables. Similar findings were returned for groups defined by clinical diagnoses. Comorbid bipolar disorder and borderline personality disorder is consistent with the formal definition of comorbidity in that, while coterminous, individuals meeting such criteria have features of two independent conditions. © The Royal College of Psychiatrists 2016.

A Review of MR Spectroscopy Studies of Pediatric Bipolar Disorder

PubMed Central

Kondo, D.G.; Hellem, T.L.; Shi, X.-F.; Sung, Y.H.; Prescot, A.P.; Kim, T.S.; Huber, R.S.; Forrest, L.N.; Renshaw, P.F.

2015-01-01

Pediatric bipolar disorder is a severe mental illness whose pathophysiology is poorly understood and for which there is an urgent need for improved diagnosis and treatment. MR spectroscopy is a neuroimaging method capable of in vivo measurement of neurochemicals relevant to bipolar disorder neurobiology. MR spectroscopy studies of adult bipolar disorder provide consistent evidence for alterations in the glutamate system and mitochondrial function. In bipolar disorder, these 2 phenomena may be linked because 85% of glucose in the brain is consumed by glutamatergic neurotransmission and the conversion of glutamate to glutamine. The purpose of this article is to review the MR spectroscopic imaging literature in pediatric bipolar disorder, at-risk samples, and severe mood dysregulation, with a focus on the published findings that are relevant to glutamatergic and mitochondrial functioning. Potential directions for future MR spectroscopy studies of the glutamate system and mitochondrial dysfunction in pediatric bipolar disorder are discussed. PMID:24557702

Foveal cone spacing and cone photopigment density difference: objective measurements in the same subjects.

PubMed

Marcos, S; Tornow, R P; Elsner, A E; Navarro, R

1997-07-01

Foveal cone spacing was measured in vivo using an objective technique: ocular speckle interferometry. Cone packing density was computed from cone spacing data. Foveal cone photopigment density difference was measured in the same subjects using retinal densitometry with a scanning laser ophthalmoscope. Both the cone packing density and cone photopigment density difference decreased sharply with increasing retinal eccentricity. From the comparison of both sets of measurements, the computed amounts of photopigment per cone increased slightly with increasing retinal eccentricity. Consistent with previous results, decreases in cone outer segment length are over-compensated by an increase in the outer segment area, at least in retinal eccentricities up to 1 deg.

A high speed and high gain CMOS receiver chip for a pulsed time-of-flight laser rangefinder

NASA Astrophysics Data System (ADS)

Yu, Jin-jin; Deng, Ruo-han; Yuan, Hong-hui; Chen, Yong-ping

2011-06-01

An integrated receiver channel for a pulsed time-of-flight (TOF) laser rangefinder has been designed. Pulsed TOF laser range finding devices using a laser diode transmitter can achieve millimeter-level distance measurement accuracy in a measurement range of several tens of meters to non-cooperative targets. The amplifier exploits the regulated cascade (RGC) configuration as the input-stage, thus achieving as large effective input trans-conductance as that of Si Bipolar or GaAs MESFET. The RGC input configuration isolates the input parasitic capacitance including photodiode capacitance from the bandwidth determination better than common-gate TIA. To enlarge the bandwidth, inductive peaking technology has been adopted. An active inductor (MOS-L) is used instead of spiral inductor in CMOS process. An R-2R resistor ladder is inserting between per-amplifier and post-amplifier as the variable attenuator for digital gain control purpose. The gain-bandwidth of a basic differential pair with resistive load is not large enough for broad band operation. A circuit solution to improve both gain and bandwidth of an amplifying stage is proposed. Traditional and modified Cherry-Hooper amplifiers are discussed and the cascading of several stages to constitute the post-amplifier is designed. The fully integrated one-chip solution is designed with Cadence IC design platform. The simulation result shows the bandwidth of the trans-impedance amplifier is 215MHz with the presence of a 2pF input capacitor and 5pF load capacitor. And the maximum trans-impedance gain is 136dB. The walk error is less than 1ns in 1:1000 dynamic range. The responsive time is less than 2.2ns.

Family Functioning and the Course of Adolescent Bipolar Disorder

ERIC Educational Resources Information Center

Sullivan, Aimee E.; Judd, Charles M.; Axelson, David A.; Miklowitz, David J.

2012-01-01

The symptoms of bipolar disorder affect and are affected by the functioning of family environments. Little is known, however, about the stability of family functioning among youth with bipolar disorder as they cycle in and out of mood episodes. This study examined family functioning and its relationship to symptoms of adolescent bipolar disorder,…

Family Intervention with a Case of Bipolar I Disorder with Family Conflict

ERIC Educational Resources Information Center

Sahu, Kamlesh Kumar

2013-01-01

Bipolar disorder is a major mental illness. Inherited treatment of bipolar disorder has been focused on pharmacological treatments. Though, psychosocial variables appear to be important antecedents of bipolar disorder, poor drug compliance, expressed emotion or faulty communication and life events play a vital role in relapse. Conflict is commonly…

Dysfunctional Cognitions among Offspring of Individuals with Bipolar Disorder.

PubMed

Ruggero, Camilo J; Bain, Kathleen M; Smith, Patrick M; Kilmer, Jared N

2015-07-01

Individuals with bipolar disorder often endorse dysfunctional beliefs consistent with cognitive models of bipolar disorder (Beck, 1976; Mansell, 2007). The present study sought to assess whether young adult offspring of those with bipolar disorder would also endorse these beliefs, independent of their own mood episode history. Participants (N = 89) were young adult college students with a parent with bipolar disorder (n = 27), major depressive disorder (MDD; n = 30), or no mood disorder (n = 32). Semi-structured interviews of the offspring were used to assess diagnoses. Dysfunctional beliefs related to Beck and colleagues' (2006) and Mansell's (2007) cognitive models were assessed. Unlike offspring of parents with MDD or no mood disorder, those with a parent with bipolar disorder endorsed significantly more dysfunctional cognitions associated with extreme appraisal of mood states, even after controlling for their own mood diagnosis. Once affected by a bipolar or depressive disorder, offspring endorsed dysfunctional cognitions across measures. Dysfunctional cognitions, particularly those related to appraisals of mood states and their potential consequences, are evident in young adults with a parent who has bipolar disorder and may represent targets for psychotherapeutic intervention.

Overlapping prefrontal systems involved in cognitive and emotional processing in euthymic bipolar disorder and following sleep deprivation: A review of functional neuroimaging studies

PubMed Central

McKenna, Benjamin S; Eyler, Lisa T

2013-01-01

Prefrontal cortex (PFC) mediated cognitive and emotional processing deficits in bipolar disorder lead to functional limitations even during periods of mood stability. Alterations of sleep and circadian functioning are well-documented in bipolar disorder, but there is little research directly examining the mechanistic role of sleep and/or circadian rhythms in the observed cognitive and emotional processing deficits. We systematically review the cognitive and emotional processing deficits reliant upon PFC functioning of euthymic patients with bipolar disorder and in healthy individuals deprived of sleep. The evidence from two parallel lines of investigation suggests that sleep and circadian rhythms may be involved in the cognitive and emotional processing deficits seen in bipolar disorder through overlapping neurobiological systems. We discuss current models of bipolar highlighting the PFC-limbic connections and discuss inclusion of sleep-related mechanisms. Sleep and circadian dysfunction is a core feature of bipolar disorder and models of neurobiological abnormalities should incorporate chronobiological measures. Further research into the role of sleep and circadian rhythms in cognition and emotional processing in bipolar disorder is warranted. PMID:22926687

Exome sequencing of a large family identifies potential candidate genes contributing risk to bipolar disorder.

PubMed

Zhang, Tianxiao; Hou, Liping; Chen, David T; McMahon, Francis J; Wang, Jen-Chyong; Rice, John P

2018-03-01

Bipolar disorder is a mental illness with lifetime prevalence of about 1%. Previous genetic studies have identified multiple chromosomal linkage regions and candidate genes that might be associated with bipolar disorder. The present study aimed to identify potential susceptibility variants for bipolar disorder using 6 related case samples from a four-generation family. A combination of exome sequencing and linkage analysis was performed to identify potential susceptibility variants for bipolar disorder. Our study identified a list of five potential candidate genes for bipolar disorder. Among these five genes, GRID1(Glutamate Receptor Delta-1 Subunit), which was previously reported to be associated with several psychiatric disorders and brain related traits, is particularly interesting. Variants with functional significance in this gene were identified from two cousins in our bipolar disorder pedigree. Our findings suggest a potential role for these genes and the related rare variants in the onset and development of bipolar disorder in this one family. Additional research is needed to replicate these findings and evaluate their patho-biological significance. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed Central

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

Dissecting disease entities out of the broad spectrum of bipolar-disorders.

PubMed

Levine, Joseph; Toker, Lilach; Agam, Galila

2018-01-01

The etiopathology of bipolar disorders is yet unraveled and new avenues should be pursued. One such avenue may be based on the assumption that the bipolar broad spectrum includes, among others, an array of rare medical disease entities. Towards this aim we propose a dissecting approach based on a search for rare medical diseases with known etiopathology which also exhibit bipolar disorders symptomatology. We further suggest that the etiopathologic mechanisms underlying such rare medical diseases may also underlie a rare variant of bipolar disorder. Such an assumption may be further reinforced if both the rare medical disease and its bipolar clinical phenotype demonstrate a] a similar mode of inheritance (i.e, autosomal dominant); b] brain involvement; and c] data implicating that the etiopathological mechanisms underlying the rare diseases affect biological processes reported to be associated with bipolar disorders and their treatment. We exemplify our suggested approach by a rare case of autosomal dominant leucodystrophy, a disease entity exhibiting nuclear lamin B1 pathology also presenting bipolar symptomatology. Copyright © 2017 Elsevier B.V. All rights reserved.

Employment outcomes in people with bipolar disorder: a systematic review.

PubMed

Marwaha, S; Durrani, A; Singh, S

2013-09-01

Employment outcome in bipolar disorder is an under investigated, but important area. The aim of this study was to identify the long-term employment outcomes of people with bipolar disorder. A systematic review using the Medline, PsychInfo and Web of Science databases. Of 1962 abstracts retrieved, 151 full text papers were read. Data were extracted from 25 papers representing a sample of 4892 people with bipolar disorder and a mean length of follow-up of 4.9 years. Seventeen studies had follow-up periods of up to 4 years and eight follow-up of 5-15 years. Most studies with samples of people with established bipolar disorder suggest approximately 40-60% of people are in employment. Studies using work functioning measures mirrored this result. Bipolar disorder appears to lead to workplace underperformance and 40-50% of people may suffer a slide in their occupational status over time. Employment levels in early bipolar disorder were higher than in more established illness. Bipolar disorder damages employment outcome in the longer term, but up to 60% of people may be in employment. Whilst further studies are necessary, the current evidence provides support for extending the early intervention paradigm to bipolar disorder. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Characteristics of stress-coping behaviors in patients with bipolar disorders.

PubMed

Moon, Eunsoo; Chang, Jae Seung; Choi, Sungwon; Ha, Tae Hyon; Cha, Boseok; Cho, Hyun Sang; Park, Je Min; Lee, Byung Dae; Lee, Young Min; Choi, Yoonmi; Ha, Kyooseob

2014-08-15

Appropriate stress-coping strategies are needed to improve the outcome in the treatment of bipolar disorders, as stressful life events may aggravate the course of the illness. The aim of this study was to compare stress-coping behaviors between bipolar patients and healthy controls. A total of 206 participants comprising 103 bipolar patients fulfilling the Diagnostic and Statistical Manual for Axis I disorder fourth edition (DSM-IV) diagnostic criteria for bipolar I and II disorders and controls matched by age and sex were included in this study. Stress-coping behaviors were assessed using a 53-item survey on a newly-designed behavioral checklist. The characteristics of stress-coping behaviors between the two groups were compared by using t-test and factor analysis. Social stress-coping behaviors such as 'journey', 'socializing with friends', and 'talking something over' were significantly less frequent in bipolar patients than controls. On the other hand, pleasurable-seeking behaviors such as 'smoking', 'masturbation', and 'stealing' were significantly more frequent in bipolar patients than controls. These results suggest that bipolar patients may have more maladaptive stress-coping strategies than normal controls. It is recommended to develop and apply psychosocial programs to reduce maladaptive stress-coping behaviors of bipolar patients. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Tissue type determination by impedance measurement: A bipolar and monopolar comparison

PubMed Central

Sharp, Jack; Bouazza-Marouf, Kaddour; Noronha, Dorita; Gaur, Atul

2017-01-01

Background: In certain medical applications, it is necessary to be able to determine the position of a needle inside the body, specifically with regards to identifying certain tissue types. By measuring the electrical impedance of specific tissue types, it is possible to determine the type of tissue the tip of the needle (or probe) is at. Materials and Methods: Two methods have been investigated for electric impedance detection; bipolar and monopolar. Commercially available needle electrodes are of a monopolar type. Although many patents exist on the bipolar setups, these have not as yet been commercialized. This paper reports a comparison of monopolar and bipolar setups for tissue type determination. In vitro experiments were carried out on pork to compare this investigation with other investigations in this field. Results: The results show that both monopolar and bipolar setups are capable of determining tissue type. However, the bipolar setup showed slightly better results; the difference between the different soft tissue type impedances was greater compared to the monopolar method. Conclusion: Both monopolar and bipolar electrical impedance setups work very similarly in inhomogeneous volumes such as biological tissue. There is a clear potential for clinical applications with impedance-based needle guidance, with both the monopolar and bipolar setups. It is, however, worth noting that the bipolar setup is more versatile. PMID:28217047

Spin orbit torque based electronic neuron

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

Sengupta, Abhronil, E-mail: asengup@purdue.edu; Choday, Sri Harsha; Kim, Yusung

2015-04-06

A device based on current-induced spin-orbit torque (SOT) that functions as an electronic neuron is proposed in this work. The SOT device implements an artificial neuron's thresholding (transfer) function. In the first step of a two-step switching scheme, a charge current places the magnetization of a nano-magnet along the hard-axis, i.e., an unstable point for the magnet. In the second step, the SOT device (neuron) receives a current (from the synapses) which moves the magnetization from the unstable point to one of the two stable states. The polarity of the synaptic current encodes the excitatory and inhibitory nature of themore » neuron input and determines the final orientation of the magnetization. A resistive crossbar array, functioning as synapses, generates a bipolar current that is a weighted sum of the inputs. The simulation of a two layer feed-forward artificial neural network based on the SOT electronic neuron shows that it consumes ∼3× lower power than a 45 nm digital CMOS implementation, while reaching ∼80% accuracy in the classification of 100 images of handwritten digits from the MNIST dataset.« less

Identifying early indicators in bipolar disorder: a qualitative study.

PubMed

Benti, Liliane; Manicavasagar, Vijaya; Proudfoot, Judy; Parker, Gordon

2014-06-01

The identification of early markers has become a focus for early intervention in bipolar disorder. Using a retrospective, qualitative methodology, the present study compares the early experiences of participants with bipolar disorder to those with unipolar depression up until their first diagnosed episode. The study focuses on differences in early home and school environments as well as putative differences in personality characteristics between the two groups. Finally we a compare and contrast prodromal symptoms in these two populations. Thirty-nine participants, 20 diagnosed with unipolar depression and 19 diagnosed with bipolar disorder, took part in the study. A semi-structured interview was developed to elicit information about participants' experiences prior to their first episode. Participants with bipolar disorder reported disruptive home environments, driven personality features, greater emotion dysregulation and adverse experiences during the school years, whereas participants with depression tended to describe more supportive home environments, and more compliant and introvert personality traits. Retrospective data collection and no corroborative evidence from other family members. No distinction was made between bipolar I and bipolar II disorder nor between melancholic and non-melancholic depression in the sample. Finally the study spanned over a 12-month period which does not allow for the possibility of diagnostic reassignment of some of the bipolar participants to the unipolar condition. These findings indicate that there may be benefits in combining both proximal and distal indicators in identifying a bipolar disorder phenotype which, in turn, may be relevant to the development of early intervention programs for young people with bipolar disorder.

Interacting Mechanisms of Impulsivity in Bipolar Disorder and Antisocial Personality Disorder

PubMed Central

Swann, Alan C.; Lijffijt, Marijn; Lane, Scott D.; Steinberg, Joel L.; Moeller, F. Gerard

2011-01-01

Background Bipolar disorder and antisocial personality disorder (ASPD) overlap in clinical characteristics and behavioral consequences. Impulsivity is prominent in both, but there is little information on how specific mechanisms of impulsivity differentiate, bridge, or underlie the disorders. Methods Subjects, all males, were controls (n=46), bipolar disorder without cluster B personality disorder (n=21), ASPD without bipolar disorder (n=50), and bipolar disorder with ASPD (n=16). Impulsivity measures were the Immediate Memory Task (IMT), a continuous performance test of response inhibition measuring ability to evaluate a stimulus before responding, and the Two Choice Impulsivity Paradigm (TCIP), a choice between smaller-sooner and larger-later reward. Data were analyzed using general linear models analysis. Results Subjects with bipolar disorder had fewer IMT correct detections and slower reaction times than controls. Reaction times were faster with combined diagnoses than in bipolar disorder alone. TCIP responding in either diagnosis alone resembled controls, but was more impulsive in combined disorders. These differences persisted after correction for age and education, which had significant independent effects. In combined ASPD and bipolar disorder, increased reaction speed, impulsive response bias, and reward-delay impulsivity occurred independent of substance-use disorder history. Conclusions Impulsivity was increased in the combined disorders over either disorder alone. Results were consistent with at least partially distinct mechanisms of impulsivity in ASPD and bipolar disorder. Compensatory mechanisms for impulsivity in uncomplicated ASPD or bipolar disorder appear to be compromised or lost when the disorders are combined. PMID:21719028

Association of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism with early-onset bipolar disorder.

PubMed

Nassan, Malik; Croarkin, Paul E; Luby, Joan L; Veldic, Marin; Joshi, Paramjit T; McElroy, Susan L; Post, Robert M; Walkup, John T; Cercy, Kelly; Geske, Jennifer R; Wagner, Karen D; Cuellar-Barboza, Alfredo B; Casuto, Leah; Lavebratt, Catharina; Schalling, Martin; Jensen, Peter S; Biernacka, Joanna M; Frye, Mark A

2015-09-01

Brain-derived neurotrophic factor (BDNF) Val66Met (rs6265) functional polymorphism has been implicated in early-onset bipolar disorder. However, results of studies are inconsistent. We aimed to further explore this association. DNA samples from the Treatment of Early Age Mania (TEAM) and Mayo Clinic Bipolar Disorder Biobank were investigated for association of rs6265 with early-onset bipolar disorder. Bipolar cases were classified as early onset if the first manic or depressive episode occurred at age ≤19 years (versus adult-onset cases at age >19 years). After quality control, 69 TEAM early-onset bipolar disorder cases, 725 Mayo Clinic bipolar disorder cases (including 189 early-onset cases), and 764 controls were included in the analysis of association, assessed with logistic regression assuming log-additive allele effects. Comparison of TEAM cases with controls suggested association of early-onset bipolar disorder with the rs6265 minor allele [odds ratio (OR) = 1.55, p = 0.04]. Although comparison of early-onset adult bipolar disorder cases from the Mayo Clinic versus controls was not statistically significant, the OR estimate indicated the same direction of effect (OR = 1.21, p = 0.19). When the early-onset TEAM and Mayo Clinic early-onset adult groups were combined and compared with the control group, the association of the minor allele rs6265 was statistically significant (OR = 1.30, p = 0.04). These preliminary analyses of a relatively small sample with early-onset bipolar disorder are suggestive that functional variation in BDNF is implicated in bipolar disorder risk and may have a more significant role in early-onset expression of the disorder. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A critical appraisal of neuroimaging studies of bipolar disorder: toward a new conceptualization of underlying neural circuitry and roadmap for future research

PubMed Central

Phillips, Mary L; Swartz, Holly A.

2014-01-01

Objective This critical review appraises neuroimaging findings in bipolar disorder in emotion processing, emotion regulation, and reward processing neural circuitry, to synthesize current knowledge of the neural underpinnings of bipolar disorder, and provide a neuroimaging research “roadmap” for future studies. Method We examined findings from all major studies in bipolar disorder that used fMRI, volumetric analyses, diffusion imaging, and resting state techniques, to inform current conceptual models of larger-scale neural circuitry abnormalities in bipolar disorder Results Bipolar disorder can be conceptualized in neural circuitry terms as parallel dysfunction in bilateral prefrontal cortical (especially ventrolateral prefrontal cortical)-hippocampal-amygdala emotion processing and emotion regulation neural circuitries, together with an “overactive” left-sided ventral striatal-ventrolateral and orbitofrontal cortical reward processing circuitry, that result in characteristic behavioral abnormalities associated with bipolar disorder: emotional lability, emotional dysregulation and heightened reward sensitivity. A potential structural basis for these functional abnormalities are gray matter decreases in prefrontal and temporal cortices, amygdala and hippocampus, and fractional anisotropy decreases in white matter tracts connecting prefrontal and subcortical regions. Conclusion Neuroimaging studies of bipolar disorder clearly demonstrate abnormalities in neural circuitries supporting emotion processing, emotion regulation and reward processing, although there are several limitations to these studies. Future neuroimaging research in bipolar disorder should include studies adopting dimensional approaches; larger studies examining neurodevelopmental trajectories in bipolar disorder and at-risk youth; multimodal neuroimaging studies using integrated systems approaches; and studies using pattern recognition approaches to provide clinically useful, individual-level data. Such studies will help identify clinically-relevant biomarkers to guide diagnosis and treatment decision-making for individuals with bipolar disorder. PMID:24626773

Cognitive and functional deficits in bipolar disorder and schizophrenia as a function of the presence and history of psychosis.

PubMed

Bowie, Christopher R; Best, Michael W; Depp, Colin; Mausbach, Brent T; Patterson, Thomas L; Pulver, Ann E; Harvey, Philip D

2018-05-18

Schizophrenia and bipolar disorder overlap considerably. Schizophrenia is a primary psychotic disorder, whereas approximately half of people with bipolar disorder will experience psychosis. In this study, we examined the extent to which cognitive and functional impairments are related to the presence and history of psychosis across the two disorders. A total of 633 participants with bipolar disorder I, schizophrenia, and schizoaffective disorder were recruited for a study on the genetics of cognition and functioning in bipolar disorder and schizophrenia. Participants were classified into five groups: bipolar disorder with current psychosis (N = 30), bipolar disorder with a history of psychosis (N = 162), bipolar disorder with no history of psychosis (N = 92), schizophrenia with current psychosis (N = 245), and schizophrenia with past psychosis (N = 104). Cognitive profiles of all groups were similar in pattern; however, both current psychosis (P < .02) and a diagnosis of schizophrenia (P < .03) were associated with greater impairment. Schizophrenia with current psychosis was also associated with a superimposed severe impairment in processing speed. Both psychosis (P < .03) and schizophrenia diagnosis (P < .01) were associated with poorer functional competence. Individuals with bipolar disorder and schizophrenia experienced similar impairments in real-world functioning if they were experiencing current psychosis (P = .32). The presence of active psychosis is an important cross-diagnostic factor in cognition and functioning in both schizophrenia and bipolar disorder. Characterization and treatment of cognition and functional deficits in bipolar disorder should consider the effects of both current and history of psychosis. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Origin and characteristics of high Shannon entropy at the pivot of locally stable rotors: insights from computational simulation.

PubMed

Ganesan, Anand N; Kuklik, Pawel; Gharaviri, Ali; Brooks, Anthony; Chapman, Darius; Lau, Dennis H; Roberts-Thomson, Kurt C; Sanders, Prashanthan

2014-01-01

Rotors are postulated to maintain cardiac fibrillation. Despite the importance of bipolar electrograms in clinical electrophysiology, few data exist on the properties of bipolar electrograms at rotor sites. The pivot of a spiral wave is characterized by relative uncertainty of wavefront propagation direction compared to the periphery. The bipolar electrograms used in electrophysiology recording encode information on both direction and timing of approaching wavefronts. To test the hypothesis that bipolar electrograms from the pivot of rotors have higher Shannon entropy (ShEn) than electrograms recorded at the periphery due to the spatial dynamics of spiral waves. We studied spiral wave propagation in 2-dimensional sheets constructed using a simple cell automaton (FitzHugh-Nagumo), atrial (Courtemanche-Ramirez-Nattel) and ventricular (Luo-Rudy) myocyte cell models and in a geometric model spiral wave. In each system, bipolar electrogram recordings were simulated, and Shannon entropy maps constructed as a measure of electrogram information content. ShEn was consistently highest in the pivoting region associated with the phase singularity of the spiral wave. This property was consistently preserved across; (i) variation of model system (ii) alterations in bipolar electrode spacing, (iii) alternative bipolar electrode orientation (iv) bipolar electrogram filtering and (v) in the presence of rotor meander. Directional activation plots demonstrated that the origin of high ShEn at the pivot was the directional diversity of wavefront propagation observed in this location. The pivot of the rotor is consistently associated with high Shannon entropy of bipolar electrograms despite differences in action potential model, bipolar electrode spacing, signal filtering and rotor meander. Maximum ShEn is co-located with the pivot for rotors observed in the bipolar electrogram recording mode, and may be an intrinsic property of spiral wave dynamic behaviour.

Association between childhood dimensions of attention deficit hyperactivity disorder and adulthood clinical severity of bipolar disorders.

PubMed

Etain, Bruno; Lajnef, M; Loftus, J; Henry, C; Raust, A; Gard, S; Kahn, J P; Leboyer, M; Scott, J; Bellivier, F

2017-04-01

Clinical features of attention deficit hyperactivity disorder can be frequently observed in cases with bipolar disorders and associated with greater severity of bipolar disorders. Although designed as a screening tool for attention deficit hyperactivity disorder, the Wender Utah Rating Scale could, given its factorial structure, be useful in investigating the early history of impulsive, inattentive or mood-related symptoms among patients with bipolar disorders. We rated the Wender Utah Rating Scale in 276 adult bipolar disorder cases and 228 healthy controls and tested its factorial structure and any associations with bipolar disorder phenomenology. We confirmed a three-factor structure for the Wender Utah Rating Scale (' impulsivity/temper', ' inattentiveness' and ' mood/self-esteem'). Cases and controls differed significantly on Wender Utah Rating Scale total score and sub-scale scores ( p-values < 10 -5 ). About 23% of bipolar disorder cases versus 5% of controls were classified as ' WURS positive' (odds ratio = 5.21 [2.73-9.95]). In bipolar disorders, higher Wender Utah Rating Scale score was associated with earlier age at onset, severity of suicidal behaviors and polysubstance misuse; multivariate analyses, controlling for age and gender, confirmed the associations with age at onset ( p = 0.001) and alcohol and substance misuse ( p = 0.001). Adults with bipolar disorders who reported higher levels of childhood symptoms on the Wender Utah Rating Scale presented a more severe expression of bipolar disorders in terms of age at onset and comorbidity. The Wender Utah Rating Scale could be employed to screen for attention deficit hyperactivity disorder but also for ' at-risk behaviors' in adult bipolar disorder cases and possibly for prodromal signs of early onset in high-risk subjects.

Hyperthyroidism and Risk for Bipolar Disorders: A Nationwide Population-Based Study

PubMed Central

Hu, Yu-Wen; Chen, Mu-Hong; Tsai, Chia-Fen; Chiang, Huey-Ling; Yeh, Chiu-Mei; Wang, Wei-Shu; Chen, Pan-Ming; Hu, Tsung-Ming; Chen, Tzeng-Ji; Su, Tung-Ping; Liu, Chia-Jen

2013-01-01

Background Thyroid disorders have long been associated with psychiatric illness, often with symptoms suggestive of mood disorders. The most common clinical features associated with hyperthyroidism are anxiety and depression. The risk of bipolar disorders, especially bipolar mania, among patients with thyroid disorders has not been well characterized. Objective We explored the relationship of hyperthyroidism and the subsequent development of bipolar disorders, and examined the risk factors for bipolar disorders in patients with hyperthyroidism. Methods We identified patients who were diagnosed with hyperthyroidism between 2000 and 2010 in the Taiwan National Health Insurance Research Database. A comparison cohort without hyperthyroidism was matched based on age, sex, and comorbidities. The occurrence of bipolar disorders was evaluated in both cohorts based on diagnosis and the use of mood stabilizer drugs. Results The hyperthyroidism cohort consisted of 21, 574 patients, and the comparison cohort consisted of 21, 574 matched control patients without hyperthyroidism. The incidence of bipolar disorders (incidence rate ratio [IRR], 2.31, 95% CI 1.80–2.99, P<.001) was higher for the hyperthyroidism patients than the control patients. Multivariate, matched regression models showed that women (HR 2.02, 95% CI 1.34–3.05, P = .001), patients with alcohol use disorders (HR 3.03, 95% CI 1.58–5.79, P = .001), and those with asthma (HR 1.70, 95% CI 1.18–2.43, P = .004) were independent risk factors for the development of bipolar disorders in hyperthyroidism patients. Conclusions Although a possibility that the diagnosis of bipolar disorders in this study actually includes "bipolar disorders due to hyperthyroidism" cannot be excluded, this study suggests that hyperthyroidism may increase the risk of developing bipolar disorders. PMID:24023669

Lamotrigine and GABAA receptor modulators interact with menstrual cycle phase and oral contraceptives to regulate mood in women with bipolar disorder.

PubMed

Robakis, Thalia K; Holtzman, Jessie; Stemmle, Pascale G; Reynolds-May, Margaret F; Kenna, Heather A; Rasgon, Natalie L

2015-04-01

To examine the occurrence of menstrually-entrained mood cycling in women with treated bipolar disorder as compared to healthy controls, and to explore whether there is a specific effect of lamotrigine in dampening menstrually-entrained cyclicity of mood. Observational comparison study of daily self-ratings of mood, sleep, and insomnia obtained over a mean of four menstrual cycles in 42 women with bipolar disorder taking lamotrigine as part of their treatment, 30 women with bipolar disorder receiving mood stabilizing regimens without lamotrigine, and 13 healthy controls, all with physiological menstrual cycles. Additional exploratory analysis of interactions between psychopharmacological regimen and hormonal contraceptive use in the group of women with bipolar disorder, with the addition of 19 women with bipolar disorder who were using hormonal contraceptives. Women treated for bipolar disorder manifested lower average mood, longer average nightly sleep duration, and greater fluctuations in mood and sleep across menstrual cycle phases than healthy controls. Women with bipolar disorder who were taking lamotrigine had less fluctuation in mood both within and across menstrual cycle phases, and were more similar to the control group than to women with bipolar disorder who were not taking lamotrigine in this respect. In addition, medications with GABA-A receptor modulating effects were found to result in improved mood ratings when combined with hormonal contraceptives. Menstrually-entrained mood fluctuation is present in women treated for bipolar disorder to a greater degree than in healthy controls. Lamotrigine may be of use in mitigating this fluctuation. GABA-A receptor modulators in general may act synergistically with hormonal contraceptives to enhance mood in women with bipolar disorder; this hypothesis merits further study. Copyright © 2014 Elsevier B.V. All rights reserved.

The role of affective temperaments assessed by the Temperament Evaluation of Memphis, Pisa and San Diego-Autoquestionnaire (TEMPS-A) in the relationship between morningness-eveningness and bipolarity.

PubMed

Chrobak, Adrian A; Tereszko, Anna; Dembinska-Krajewska, Daria; Arciszewska, Aleksandra; Dopierała, Ewa; Siwek, Marcin; Dudek, Dominika; Rybakowski, Janusz K

2018-05-01

Growing number of studies indicates a link between eveningness chronotype, affective temperaments and bipolarity, both in patients with mood disorders and in general population. Given these tripartite associations, we hypothesized that the effect of circadian preferences on the bipolarity may be mediated by the temperamental traits. The study included 1449 subjects (402 men and 1047 women). They all fulfilled a web-based questionnaire, consisting of the Composite Scale of Morningness (CSM), Mood Disorder Questionnaire (MDQ), Hypomania Checklist-32 (HCL-32) and the Temperament Evaluation of the Memphis, Pisa and San Diego-Autoquestionnaire (TEMPS-A). The role of temperamental traits in the relationship between morningness-eveningness and bipolarity was assessed using mediation analysis. Morningness is correlated with lower bipolarity measured by the MDQ and HCL-32, and to lower scores of depressive, cyclothymic, irritable and anxious temperaments of the TEMPS-A. There is no significant association between morningness and hyperthymic traits. Cyclothymic and irritable traits are full mediators of the association between chronotype and bipolarity, influencing bipolarity independently from circadian preferences. Depressive and anxious traits are partial mediators of this association, increasing the effect of eveningness on bipolarity. The indirectness of the findings in the web-based study and disproportion of participants' gender. Our study confirmed that eveningness is associated with bipolarity. In case of depressive and anxious temperaments, bipolarity is associated stronger with eveningness than with the TEMPS-A scores. On the other hand, cyclothymic and irritable temperaments were associated with bipolarity independently from circadian preferences. Copyright © 2018 Elsevier B.V. All rights reserved.

Hyperthyroidism and risk for bipolar disorders: a nationwide population-based study.

PubMed

Hu, Li-Yu; Shen, Cheng-Che; Hu, Yu-Wen; Chen, Mu-Hong; Tsai, Chia-Fen; Chiang, Huey-Ling; Yeh, Chiu-Mei; Wang, Wei-Shu; Chen, Pan-Ming; Hu, Tsung-Ming; Chen, Tzeng-Ji; Su, Tung-Ping; Liu, Chia-Jen

2013-01-01

Thyroid disorders have long been associated with psychiatric illness, often with symptoms suggestive of mood disorders. The most common clinical features associated with hyperthyroidism are anxiety and depression. The risk of bipolar disorders, especially bipolar mania, among patients with thyroid disorders has not been well characterized. We explored the relationship of hyperthyroidism and the subsequent development of bipolar disorders, and examined the risk factors for bipolar disorders in patients with hyperthyroidism. We identified patients who were diagnosed with hyperthyroidism between 2000 and 2010 in the Taiwan National Health Insurance Research Database. A comparison cohort without hyperthyroidism was matched based on age, sex, and comorbidities. The occurrence of bipolar disorders was evaluated in both cohorts based on diagnosis and the use of mood stabilizer drugs. The hyperthyroidism cohort consisted of 21, 574 patients, and the comparison cohort consisted of 21, 574 matched control patients without hyperthyroidism. The incidence of bipolar disorders (incidence rate ratio [IRR], 2.31, 95% CI 1.80-2.99, P<.001) was higher for the hyperthyroidism patients than the control patients. Multivariate, matched regression models showed that women (HR 2.02, 95% CI 1.34-3.05, P = .001), patients with alcohol use disorders (HR 3.03, 95% CI 1.58-5.79, P = .001), and those with asthma (HR 1.70, 95% CI 1.18-2.43, P = .004) were independent risk factors for the development of bipolar disorders in hyperthyroidism patients. Although a possibility that the diagnosis of bipolar disorders in this study actually includes "bipolar disorders due to hyperthyroidism" cannot be excluded, this study suggests that hyperthyroidism may increase the risk of developing bipolar disorders.

Increased prospective health service use for depression among adults with childhood onset bipolar disorder.

PubMed

Sala, Regina; Goldstein, Benjamin I; Wang, Shuai; Flórez-Salamanca, Ludwing; Iza, Miren; Blanco, Carlos

2013-11-01

To examine the prospective relationship between age of onset of bipolar disorder and the demographic and clinical characteristics, treatment, new onset of psychiatric comorbidity, and psychosocial functioning among adults with bipolar disorder. As part of the National Epidemiologic Survey on Alcohol and Related Conditions, 1600 adults who met lifetime Statistical Manual of Mental Disorders, 4th edition criteria for bipolar disorder-I (n = 1172) and bipolar disorder-II (n = 428) were included. Individuals were evaluated using the Alcohol Use Disorder and Associated Disabilities Interview Schedule-IV version for Diagnostic and Statistical Manual of Mental Disorders, 4th edition, and data were analyzed from Waves 1 and 2, approximately 3 years apart. Individuals with bipolar disorder were divided into three age at onset groups: childhood (<13 years old, n = 115), adolescence (13-18 years old, n = 396), and adulthood (>19 year old, n = 1017). After adjusting for confounding factors, adults with childhood-onset bipolar disorder were more likely to see a counselor, have been hospitalized, and have received emergency room treatment for depression compared with those with adulthood-onset bipolar disorder. By contrast, there were no differences in the severity of mania or hypomania, new onset of comorbidity, and psychosocial functioning by age of bipolar disorder onset. Childhood-onset bipolar disorder is prospectively associated with seeking treatment for depression, an important proxy for depressive severity. Longitudinal studies are needed in order to determine whether prompt identification, accurate diagnosis, and early intervention can serve to mitigate the burden of childhood onset on the long-term depressive burden of bipolar disorder. Copyright © 2013 Mosby, Inc. All rights reserved.

Risk factors for secondary substance use disorders in people with childhood and adolescent-onset bipolar disorder: opportunities for prevention.

PubMed

Kenneson, Aileen; Funderburk, Jennifer S; Maisto, Stephen A

2013-07-01

Compared to other mental illnesses, bipolar disorder is associated with a disproportionately high rate of substance use disorders (SUDs), and the co-occurrence is associated with significant morbidity and mortality. Early diagnosis of primary bipolar disorder may provide opportunities for SUD prevention, but little is known about the risk factors for secondary SUD among individuals with bipolar disorder. The purposes of this study were to describe the population of people with childhood and adolescent-onset primary bipolar disorder, and to identify risk factors for secondary SUD in this population. Using data collected from the National Comorbidity Survey Replication study, we identified 158 individuals with childhood-onset (<13 years) or adolescent-onset (13-18 years) primary bipolar disorder (I, II or subthreshold). Survival analysis was used to identify risk factors for SUD. Compared to adolescent-onset, people with childhood-onset bipolar disorder had increased likelihoods of attention deficit hyperactivity disorder (ADHD) (adjusted odds ratio=2.81) and suicide attempt (aOR=3.61). Males were more likely than females to develop SUD, and did so at a faster rate. Hazard ratios of risk factors for SUD were: lifetime oppositional defiant disorder (2.048), any lifetime anxiety disorder (3.077), adolescent-onset bipolar disorder (1.653), and suicide attempt (15.424). SUD was not predicted by bipolar disorder type, family history of bipolar disorder, hospitalization for a mood episode, ADHD or conduct disorder. As clinicians struggle to help individuals with bipolar disorder, this study provides information that might be useful in identifying individuals at higher risk for SUD. Future research can examine whether targeting these risk factors may help prevent secondary SUD. Published by Elsevier Inc.

Bipolar disorder and the risk of fracture: A nationwide population-based cohort study.

PubMed

Su, Jian-An; Cheng, Bi-Hua; Huang, Yin-Cheng; Lee, Chuan-Pin; Yang, Yao-Hsu; Lu, Mong-Liang; Hsu, Chung-Yao; Lee, Yena; McIntyre, Roger S; Chin Lin, Tzu; Chin-Hung Chen, Vincent

2017-08-15

The co-primary aims are: 1) to compare the risk of fracture between adults with bipolar disorder and those without bipolar disorder; and 2) to assess whether lithium, anticonvulsants and antipsychotics reduce risk of fracture among individuals with bipolar disorder. The analysis herein is a population-based retrospective cohort study, utilizing the National Health Insurance (NHI) medical claims data collected between 1997 and 2013 in Taiwan. We identified 3705 cases with incident diagnoses of bipolar disorder during study period and 37,050 matched controls without bipolar diagnoses. Incident diagnosis of fracture was operationalized as any bone fracture after the diagnosis of bipolar disorder or after the matched index date for controls. Bipolar patients had significantly higher risk of facture when compared to matched controls (17.6% versus 11.7%, respectively p<0.001). The hazard ratio (HR) was 1.33 (95% confidence interval [CI]＝1.23-1.48, p<0.001) after adjusting for covariates. Persons with bipolar disorder and a prior history of psychiatric hospitalization were had higher risk for bone fracture than those without prior history of psychiatric hospitalization when compared to match controls. Higher cumulative dose of antipsychotics or mood stabilizers did not increase the risk of fracture. The diagnoses of bipolar disorder were not confirmed with structured clinical interview. Drug adherence, exact exposure dosage, smoking, lifestyle, nutrition and exercise habits were unable to be assessed in our dataset. Bipolar disorder is associated with increased risk of fracture, and higher cumulative dose of mood stabilizers and antipsychotics did not further increase the risk of fracture. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Pérez, Juan J.; Pérez-Cajaraville, Juan J.; Muñoz, Víctor

Purpose: Pulsed RF (PRF) is a nonablative technique for treating neuropathic pain. Bipolar PRF application is currently aimed at creating a “strip lesion” to connect the electrode tips; however, the electrical and thermal performance during bipolar PRF is currently unknown. The objective of this paper was to study the temperature and electric field distributions during bipolar PRF. Methods: The authors developed computer models to study temperature and electric field distributions during bipolar PRF and to assess the possible ablative thermal effect caused by the accumulated temperature spikes, along with any possible electroporation effects caused by the electrical field. The authorsmore » also modeled the bipolar ablative mode, known as bipolar Continuous Radiofrequency (CRF), in order to compare both techniques. Results: There were important differences between CRF and PRF in terms of electrical and thermal performance. In bipolar CRF: (1) the initial temperature of the tissue impacts on temperature progress and hence on the thermal lesion dimension; and (2) at 37 °C, 6-min of bipolar CRF creates a strip thermal lesion between the electrodes when these are separated by a distance of up to 20 mm. In bipolar PRF: (1) an interelectrode distance shorter than 5 mm produces thermal damage (i.e., ablative effect) in the intervening tissue after 6 min of bipolar RF; and (2) the possible electroporation effect (electric fields higher than 150 kV m{sup −1}) would be exclusively circumscribed to a very small zone of tissue around the electrode tip. Conclusions: The results suggest that (1) the clinical parameters considered to be suitable for bipolar CRF should not necessarily be considered valid for bipolar PRF, and vice versa; and (2) the ablative effect of the CRF mode is mainly due to its much greater level of delivered energy than is the case in PRF, and therefore at same applied energy levels, CRF, and PRF are expected to result in same outcomes in terms of thermal damage zone dimension.« less

Identification of Susceptible Loci and Enriched Pathways for Bipolar II Disorder Using Genome-Wide Association Studies.

PubMed

Kao, Chung-Feng; Chen, Hui-Wen; Chen, Hsi-Chung; Yang, Jenn-Hwai; Huang, Ming-Chyi; Chiu, Yi-Hang; Lin, Shih-Ku; Lee, Ya-Chin; Liu, Chih-Min; Chuang, Li-Chung; Chen, Chien-Hsiun; Wu, Jer-Yuarn; Lu, Ru-Band; Kuo, Po-Hsiu

2016-12-01

This study aimed to identify susceptible loci and enriched pathways for bipolar disorder subtype II. We conducted a genome-wide association scan in discovery samples with 189 bipolar disorder subtype II patients and 1773 controls, and replication samples with 283 bipolar disorder subtype II patients and 500 controls in a Taiwanese Han population using Affymetrix Axiom Genome-Wide CHB1 Array. We performed single-marker and gene-based association analyses, as well as calculated polygeneic risk scores for bipolar disorder subtype II. Pathway enrichment analyses were employed to reveal significant biological pathways. Seven markers were found to be associated with bipolar disorder subtype II in meta-analysis combining both discovery and replication samples (P<5.0×10 -6 ), including markers in or close to MYO16, HSP90AB3P, noncoding gene LOC100507632, and markers in chromosomes 4 and 10. A novel locus, ETF1, was associated with bipolar disorder subtype II (P<6.0×10 -3 ) in gene-based association tests. Results of risk evaluation demonstrated that higher genetic risk scores were able to distinguish bipolar disorder subtype II patients from healthy controls in both discovery (P=3.9×10 -4 ~1.0×10 -3 ) and replication samples (2.8×10 -4 ~1.7×10 -3 ). Genetic variance explained by chip markers for bipolar disorder subtype II was substantial in the discovery (55.1%) and replication (60.5%) samples. Moreover, pathways related to neurodevelopmental function, signal transduction, neuronal system, and cell adhesion molecules were significantly associated with bipolar disorder subtype II. We reported novel susceptible loci for pure bipolar subtype II disorder that is less addressed in the literature. Future studies are needed to confirm the roles of these loci for bipolar disorder subtype II. © The Author 2016. Published by Oxford University Press on behalf of CINP.

Is impulsivity a common trait in bipolar and unipolar disorders?

PubMed

Henna, Elaine; Hatch, John P; Nicoletti, Mark; Swann, Alan C; Zunta-Soares, Giovana; Soares, Jair C

2013-03-01

  Impulsivity is increased in bipolar and unipolar disorders during episodes and is associated with substance abuse disorders and suicide risk. Impulsivity between episodes predisposes to relapses and poor therapeutic compliance. However, there is little information about impulsivity during euthymia in mood disorders. We sought to investigate trait impulsivity in euthymic bipolar and unipolar disorder patients, comparing them to healthy individuals and unaffected relatives of bipolar disorder patients.   Impulsivity was evaluated by the Barratt Impulsiveness Scale (BIS-11A) in 54 bipolar disorder patients, 25 unipolar disorder patients, 136 healthy volunteers, and 14 unaffected relatives. The BIS-11A mean scores for all four groups were compared through the Games-Howell test for all possible pairwise combinations. Additionally, we compared impulsivity in bipolar and unipolar disorder patients with and without a history of suicide attempt and substance abuse disorder.   Bipolar and unipolar disorder patients scored significantly higher than the healthy controls and unaffected relatives on all measures of the BIS-11A except for attentional impulsivity. On the attentional impulsivity measures there were no differences among the unaffected relatives and the bipolar and unipolar disorder groups, but all three of these groups scored higher than the healthy participant group. There was no difference in impulsivity between bipolar and unipolar disorder subjects with and without suicide attempt. However, impulsivity was higher among bipolar and unipolar disorder subjects with past substance use disorder compared to patients without such a history.   Questionnaire-measured impulsivity appears to be relatively independent of mood state in bipolar and unipolar disorder patients; it remains elevated in euthymia and is higher in individuals with past substance abuse. Elevated attentional and lower non-planning impulsivity in unaffected relatives of bipolar disorder patients distinguished them from healthy participants, suggesting that increased attentional impulsivity may predispose to development of affective disorders, while reduced attentional impulsivity may be protective. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

Early-Onset Bipolar Disorder: Characteristics and Outcomes in the Clinic.

PubMed

Connor, Daniel F; Ford, Julian D; Pearson, Geraldine S; Scranton, Victoria L; Dusad, Asha

2017-12-01

To assess patient characteristics and clinician-rated outcomes for children diagnosed with early-onset bipolar disorder in comparison to a depressive disorders cohort from a single clinic site. To assess predictors of bipolar treatment response. Medical records from 714 consecutive pediatric patients evaluated and treated at an academic tertiary child and adolescent psychiatry clinic between 2006 and 2012 were reviewed. Charts of bipolar children (n = 49) and children with depressive disorders (n = 58) meeting study inclusion/exclusion criteria were compared on variables assessing clinical characteristics, treatments, and outcomes. Outcomes were assessed by using pre- and post-Clinical Global Impressions (CGI)-Severity and Children's Global Assessment Scale (CGAS) scores, and a CGI-Improvement score ≤2 at final visit determined responder status. Bipolar outcome predictors were assessed by using multiple linear regression. Clinic prevalence rates were 6.9% for early-onset bipolar disorder and 1.5% for very early-onset bipolar disorder. High rates of comorbid diagnoses, symptom severity, parental stress, and child high-risk behaviors were found in both groups. The bipolar cohort had higher rates of aggression and higher lifetime systems of care utilization. The final CGI and CGAS outcomes for unipolar depression patients differed statistically significantly from those for the bipolar cohort, reflecting better clinical status and more improvement at outcome for the depression patients. Both parent-reported Child Behavior Checklist total T-score at clinic admission and the number of lifetime systems-of-care for the child were significantly and inversely associated with improvement for the bipolar cohort. Early-onset bipolar disorder is a complex and heterogeneous psychiatric disorder. Evidence-based treatment should emphasize psychopharmacology with adjunctive family and individual psychotherapy. Strategies to improve engagement in treatment may be especially important. Given high rates of high-risk behaviors in these youth, regular mental health follow-up to assess safety is important. Additional evidence-based treatments for pediatric bipolar disorder are needed.

Bipolar Disorder and Early Affective Trauma.

PubMed

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 worse prognosis. In further studies attention should be paid to the age of trauma occurrence and the definition of trauma. The findings also support the importance of additional psychoanalytic oriented psychotherapy for the treatment of bipolar disorder.

Genetic Risk Score Analysis in Early-Onset Bipolar Disorder

PubMed Central

Croarkin, Paul E.; Luby, Joan L.; Cercy, Kelly; Geske, Jennifer R.; Veldic, Marin; Simonson, Matthew; Joshi, Paramjit T.; Wagner, Karen Dineen; Walkup, John T.; Nassan, Malik M.; Cuellar-Barboza, Alfredo B.; Casuto, Leah; McElroy, Susan L.; Jensen, Peter S.; Frye, Mark A.; Biernacka, Joanna M.

2018-01-01

Objective In this study, we performed a candidate genetic risk score (GRS) analysis of early-onset bipolar disorder. Method Treatment of Early Age Mania (TEAM) study enrollment and sample collection took place from 2003–2008. Mayo Clinic Bipolar Biobank samples were collected from 2009–2013. Genotyping and analyses for the present study took place from 2013–2014. The diagnosis of bipolar disorder was based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria. Eight single-nucleotide polymorphisms (SNPs), previously reported in genome-wide association studies to be associated with bipolar disorder, were chosen for GRS analysis in early-onset bipolar disease. These SNPs map to 3 genes: CACNA1C (calcium channel, voltage-dependent, L type, alpha 1C subunit), ANK3 (ankyrin-3, node of Ranvier [ankyrin G]), and ODZ4 (teneurin transmembrane protein 4 [formerly “odz, odd Oz/ten-m homolog 4 {Drosophila}, ODZ4”]). The 8 candidate SNPs were genotyped in patients from the TEAM study (n=69), adult patients with bipolar disorder (n=732) including a subset with early-onset illness [n=192]), and healthy controls (n=776). GRS analyses were performed comparing early-onset cases with controls. In addition, associations of early-onset BD with individual SNPs and haplotypes were explored. Results GRS analysis revealed associations of the risk score with early-onset bipolar disorder (P=.01). Gene-level haplotype analysis comparing TEAM patients with controls suggested association of early-onset bipolar disorder with a CACNA1C haplotype (global test, P=.01). At the level of individual SNPs, comparison of TEAM cases with healthy controls provided nominally significant evidence for association of SNP rs10848632 in CACNA1C with early-onset bipolar disorder (P=.017), which did not remain significant after correction for multiple comparisons. Conclusion These preliminary analyses suggest that previously identified bipolar disorder risk loci, especially CACNA1C, have a role in early-onset bipolar disorder, possibly with stronger effects than for late-onset bipolar disorder. PMID:28199072

Does psychomotor agitation in major depressive episodes indicate bipolarity? Evidence from the Zurich Study.

PubMed

Angst, Jules; Gamma, Alex; Benazzi, Franco; Ajdacic, Vladeta; Rössler, Wulf

2009-02-01

Kraepelin's partial interpretation of agitated depression as a mixed state of "manic-depressive insanity" (including the current concept of bipolar disorder) has recently been the focus of much research. This paper tested whether, how, and to what extent both psychomotor symptoms, agitation and retardation in depression are related to bipolarity and anxiety. The prospective Zurich Study assessed psychiatric and somatic syndromes in a community sample of young adults (N = 591) (aged 20 at first interview) by six interviews over 20 years (1979-1999). Psychomotor symptoms of agitation and retardation were assessed by professional interviewers from age 22 to 40 (five interviews) on the basis of the observed and reported behaviour within the interview section on depression. Psychiatric diagnoses were strictly operationalised and, in the case of bipolar-II disorder, were broader than proposed by DSM-IV-TR and ICD-10. As indicators of bipolarity, the association with bipolar disorder, a family history of mania/hypomania/cyclothymia, together with hypomanic and cyclothymic temperament as assessed by the general behavior inventory (GBI) [15], and mood lability (an element of cyclothymic temperament) were used. Agitated and retarded depressive states were equally associated with the indicators of bipolarity and with anxiety. Longitudinally, agitation and retardation were significantly associated with each other (OR = 1.8, 95% CI = 1.0-3.2), and this combined group of major depressives showed stronger associations with bipolarity, with both hypomanic/cyclothymic and depressive temperamental traits, and with anxiety. Among agitated, non-retarded depressives, unipolar mood disorder was even twice as common as bipolar mood disorder. Combined agitated and retarded major depressive states are more often bipolar than unipolar, but, in general, agitated depression (with or without retardation) is not more frequently bipolar than retarded depression (with or without agitation), and pure agitated depression is even much less frequently bipolar than unipolar. The findings do not support the hypothesis that agitated depressive syndromes are mixed states. The results are limited to a population up to the age of 40; bipolar-I disorders could not be analysed (small N).

Re-evaluating the prevalence of and diagnostic composition within the broad clinical spectrum of bipolar disorders.

PubMed

Akiskal, H S; Bourgeois, M L; Angst, J; Post, R; Möller, H; Hirschfeld, R

2000-09-01

Until recently it was believed that no more than 1% of the general population has bipolar disorder. Emerging transatlantic data are beginning to provide converging evidence for a higher prevalence of up to at least 5%. Manic states, even those with mood-incongruent features, as well as mixed (dysphoric) mania, are now formally included in both ICD-10 and DSM-IV. Mixed states occur in an average of 40% of bipolar patients over a lifetime; current evidence supports a broader definition of mixed states consisting of full-blown mania with two or more concomitant depressive symptoms. The largest increase in prevalence rates, however, is accounted for by 'softer' clinical expressions of bipolarity situated between the extremes of full-blown bipolar disorder where the person has at least one manic episode (bipolar I) and strictly defined unipolar major depressive disorder without personal or family history for excited periods. Bipolar II is the prototype for these intermediary conditions with major depressions and history of spontaneous hypomanic episodes; current evidence indicates that most hypomanias pursue a recurrent course and that their usual duration is 1-3 days, falling below the arbitrary 4-day cutoff required in DSM-IV. Depressions with antidepressant-associated hypomania (sometimes referred to as bipolar III) also appear, on the basis of extensive international research neglected by both ICD-10 and DSM-IV, to belong to the clinical spectrum of bipolar disorders. Broadly defined, the bipolar spectrum in studies conducted during the last decade accounts for 30-55% of all major depressions. Rapid-cycling, defined as alternation of depressive and excited (at least four per year), more often arise from a bipolar II than a bipolar I baseline; such cycling does not in the main appear to be a distinct clinical subtype - but rather a transient complication in 20% in the long-term course of bipolar disorder. Major depressions superimposed on cyclothymic oscillations represent a more severe variant of bipolar II, often mistaken for borderline or other personality disorders in the dramatic cluster. Moreover, atypical depressive features with reversed vegetative signs, anxiety states, as well as alcohol and substance abuse comorbidity, is common in these and other bipolar patients. The proper recognition of the entire clinical spectrum of bipolarity behind such 'masks' has important implications for psychiatric research and practice. Conditions which require further investigation include: (1) major depressive episodes where hyperthymic traits - lifelong hypomanic features without discrete hypomanic episodes - dominate the intermorbid or premorbid phases; and (2) depressive mixed states consisting of few hypomanic symptoms (i.e., racing thoughts, sexual arousal) during full-blown major depressive episodes - included in Kraepelin's schema of mixed states, but excluded by DSM-IV. These do not exhaust all potential diagnostic entities for possible inclusion in the clinical spectrum of bipolar disorders: the present review did not consider cyclic, seasonal, irritable-dysphoric or otherwise impulse-ridden, intermittently explosive or agitated psychiatric conditions for which the bipolar connection is less established. The concept of bipolar spectrum as used herein denotes overlapping clinical expressions, without necessarily implying underlying genetic homogeneity. In the course of the illness of the same patient, one often observes the varied manifestations described above - whether they be formal diagnostic categories or those which have remained outside the official nosology. Some form of life charting of illness with colored graphic representation of episodes, stressors, and treatments received can be used to document the uniquely varied course characteristic of each patient, thereby greatly enhancing clinical evaluation.

Biochemical Characterization of Cone Cyclic Nucleotide-gated (CNG) Channel Using the Infrared Fluorescence Detection System

PubMed Central

Ding, Xi-Qin; Matveev, Alexander; Singh, Anil; Komori, Naoka; Matsumoto, Hiroyuki

2012-01-01

Cone vision mediated by photoreceptor cyclic nucleotide-gated (CNG) channel is essential for central and color vision and visual acuity. Cone CNG channel is composed of two structurally related subunit types, CNGA3 and CNGB3. Naturally occurring mutations in cone CNG channel are associated with a variety of cone diseases including achromatopsia, progressive cone dystrophy, and some maculopathies. Nevertheless, our understanding of the structure of cone CNG channel is quite limited. This is, in part, due to the challenge of studying cones in a rod-dominant mammalian retina. We have demonstrated a robust expression of cone CNG channel and lack of rod CNG channel in the cone-dominant Nrl−/− retina and shown that the Nrl−/− mouse line is a valuable model to study cone CNG channel. This work examined the complex structure of cone CNG channel using infrared fluorescence Western detection combined with chemical cross-linking and blue native-PAGE. Our results suggest that the native cone CNG channel is a heterotetrameric complex likely at a stoichiometry of three CNGA3 and one CNGB3. PMID:22183405

Six different roles for crossover inhibition in the retina: correcting the nonlinearities of synaptic transmission.

PubMed

Werblin, Frank S

2010-03-01

Early retinal studies categorized ganglion cell behavior as either linear or nonlinear and rectifying as represented by the familiar X- and Y-type ganglion cells in cat. Nonlinear behavior is in large part a consequence of the rectifying nonlinearities inherent in synaptic transmission. These nonlinear signals underlie many special functions in retinal processing, including motion detection, motion in motion, and local edge detection. But linear behavior is also required for some visual processing tasks. For these tasks, the inherently nonlinear signals are "linearized" by "crossover inhibition." Linearization utilizes a circuitry whereby nonlinear ON inhibition adds with nonlinear OFF excitation or ON excitation adds with OFF inhibition to generate a more linear postsynaptic voltage response. Crossover inhibition has now been measured in most bipolar, amacrine, and ganglion cells. Functionally crossover inhibition enhances edge detection, allows ganglion cells to recognize luminance-neutral patterns with their receptive fields, permits ganglion cells to distinguish contrast from luminance, and maintains a more constant conductance during the light response. In some cases, crossover extends the operating range of cone-driven OFF ganglion cells into the scotopic levels. Crossover inhibition is also found in neurons of the lateral geniculate nucleus and V1.

Subcortical Gray Matter Volume Abnormalities in Healthy Bipolar Offspring: Potential Neuroanatomical Risk Marker for Bipolar Disorder?

ERIC Educational Resources Information Center

Ladouceur, Cecile D.; Almeida, Jorge R. C.; Birmaher, Boris; Axelson, David A.; Nau, Sharon; Kalas, Catherine; Monk, Kelly; Kupfer, David J.; Phillips, Mary L.

2008-01-01

A study is conducted to examine the extent to which bipolar disorder (BD) is associated with gray matter volume abnormalities in brain regions in healthy bipolar offspring relative to age-matched controls. Results show increased gray matter volume in the parahippocampus/hippocampus in healthy offspring at genetic risk for BD.

Examining the Validity of Cyclothymic Disorder in a Youth Sample: Replication and Extension

ERIC Educational Resources Information Center

Van Meter, Anna; Youngstrom, Eric A.; Demeter, Christine; Findling, Robert L.

2013-01-01

DSM-IV-TR defines four subtypes of bipolar disorder (BP): bipolar I, bipolar II, cyclothymic disorder and bipolar not otherwise specified (NOS). However, cyclothymic disorder in children is rarely researched, or often subsumed in an "NOS" category. The present study tests the replicability of findings from an earlier study, and expands on the…

Practice Parameter for the Assessment and Treatment of Children and Adolescents with Bipolar Disorder

ERIC Educational Resources Information Center

Journal of the American Academy of Child and Adolescent Psychiatry, 2007

2007-01-01

This practice parameter reviews the literature on the assessment and treatment of children and adolescents with bipolar disorder. The parameter focuses primarily on bipolar 1 disorder because that is the type most often studied in juveniles. The presentation of bipolar disorder in youth, especially children, is often considered atypical compared…

Parenting among Mothers with Bipolar Disorder: Strengths, Challenges, and Service Needs

ERIC Educational Resources Information Center

Venkataraman, Meenakshi; Ackerson, Barry J.

2008-01-01

Bipolar disorder is a severe form of mental illness with a primary disruption in mood. With fluctuating phases of mania and depression, bipolar disorder can have a serious impact on all activities of daily living, including parenting. Ten mothers with bipolar disorder were interviewed to understand their strengths, challenges, and service needs in…

Attention and Memory Biases in the Offspring of Parents with Bipolar Disorder: Indications from a Pilot Study

ERIC Educational Resources Information Center

Gotlib, Ian H.; Traill, Saskia K.; Montoya, Rebecca L.; Joormann, Jutta; Chang, Kiki

2005-01-01

Background: Although children of bipolar parents are at heightened risk for developing emotional disorders, the processes underlying this vulnerability are not well understood. This study examined biases in the processing of emotional stimuli as a potential vulnerability marker of bipolar disorder. Methods: Sixteen children of bipolar parents who…

Design concepts of high power bipolar rechargeable lithium battery

NASA Technical Reports Server (NTRS)

Shen, David H.; Halpert, Gerald

1993-01-01

The present study shows that current bipolar Li/TiS2 batteries using a 0.38 mm thick TiS2 bipolar plate can yield moderate specific power and also high specific energy battery. The computer design studies project that a 100 V, 10 A h bipolar Li/TiS2 battery can achieve 150 W h/kg, 210 W h/l, and 150 W/kg. The unoptimized experimental bipolar Li/TiS2 batteries (3 cells, 90 mA h) exhibited 47 W h/kg, 90 W h/l, and 140 W/kg. Preliminary results on the cycleability of the bipolar batteries are demonstrated. The results also show that enhanced rate capability can be achieved by using pulse discharge and longer rest period between pulses.

Primate Short-Wavelength Cones Share Molecular Markers with Rods

PubMed Central

Craft, Cheryl M.; Huang, Jing; Possin, Daniel E.; Hendrickson, Anita

2015-01-01

Macaca, Callithrix jacchus marmoset monkey, Pan troglodytes chim- panzee and human retinas were examined to define if short wavelength (S) cones share molecular markers with L&M cone or rod photoreceptors. S cones showed consistent differences in their immunohistochemical staining and expression levels compared to L&M cones for “rod” Arrestin1 (S-Antigen), “cone” Arrestin4, cone alpha transducin, and Calbindin. Our data verify a similar pattern of expression in these primate retinas and provide clues to the structural divergence of rods and S cones versus L&M cones, suggesting S cone retinal function is “intermediate” between them. PMID:24664680

An Analysis Model for Water Cone Subsidence in Bottom Water Drive Reservoirs

NASA Astrophysics Data System (ADS)

Wang, Jianjun; Xu, Hui; Wu, Shucheng; Yang, Chao; Kong, lingxiao; Zeng, Baoquan; Xu, Haixia; Qu, Tailai

2017-12-01

Water coning in bottom water drive reservoirs, which will result in earlier water breakthrough, rapid increase in water cut and low recovery level, has drawn tremendous attention in petroleum engineering field. As one simple and effective method to inhibit bottom water coning, shut-in coning control is usually preferred in oilfield to control the water cone and furthermore to enhance economic performance. However, most of the water coning researchers just have been done on investigation of the coning behavior as it grows up, the reported studies for water cone subsidence are very scarce. The goal of this work is to present an analytical model for water cone subsidence to analyze the subsidence of water cone when the well shut in. Based on Dupuit critical oil production rate formula, an analytical model is developed to estimate the initial water cone shape at the point of critical drawdown. Then, with the initial water cone shape equation, we propose an analysis model for water cone subsidence in bottom water reservoir reservoirs. Model analysis and several sensitivity studies are conducted. This work presents accurate and fast analytical model to perform the water cone subsidence in bottom water drive reservoirs. To consider the recent interests in development of bottom drive reservoirs, our approach provides a promising technique for better understanding the subsidence of water cone.

Gene Therapy Rescues Cone Structure and Function in the 3-Month-Old rd12 Mouse: A Model for Midcourse RPE65 Leber Congenital Amaurosis

PubMed Central

Li, Xia; Li, Wensheng; Dai, Xufeng; Kong, Fansheng; Zheng, Qinxiang; Zhou, Xiangtian; Lü, Fan; Chang, Bo; Rohrer, Bärbel; Hauswirth, William. W.; Qu, Jia; Pang, Ji-jing

2011-01-01

Purpose. RPE65 function is necessary in the retinal pigment epithelium (RPE) to generate chromophore for all opsins. Its absence results in vision loss and rapid cone degeneration. Recent Leber congenital amaurosis type 2 (LCA with RPE65 mutations) phase I clinical trials demonstrated restoration of vision on RPE65 gene transfer into RPE cells overlying cones. In the rd12 mouse, a naturally occurring model of RPE65-LCA early cone degeneration was observed; however, some peripheral M-cones remained. A prior study showed that AAV-mediated RPE65 expression can prevent early cone degeneration. The present study was conducted to test whether the remaining cones in older rd12 mice can be rescued. Methods. Subretinal treatment with the scAAV5-smCBA-hRPE65 vector was initiated at postnatal day (P)14 and P90. After 2 months, electroretinograms were recorded, and cone morphology was analyzed by using cone-specific peanut agglutinin and cone opsin–specific antibodies. Results. Cone degeneration started centrally and spread ventrally, with cells losing cone-opsin staining before that for the PNA-lectin–positive cone sheath. Gene therapy starting at P14 resulted in almost wild-type M- and S-cone function and morphology. Delaying gene-replacement rescued the remaining M-cones, and most important, more M-cone opsin–positive cells were identified than were present at the onset of gene therapy, suggesting that opsin expression could be reinitiated in cells with cone sheaths. Conclusions. The results support and extend those of the previous study that gene therapy can stop early cone degeneration, and, more important, they provide proof that delayed treatment can restore the function and morphology of the remaining cones. These results have important implications for the ongoing LCA2 clinical trials. PMID:21169527

Geomorphometric variability of "monogenetic" volcanic cones: Evidence from Mauna Kea, Lanzarote and experimental cones

NASA Astrophysics Data System (ADS)

Kervyn, M.; Ernst, G. G. J.; Carracedo, J.-C.; Jacobs, P.

2012-01-01

Volcanic cones are the most common volcanic constructs on Earth. Their shape can be quantified using two morphometric ratios: the crater/cone base ratio (W cr/W co) and the cone height/width ratio (H co/W co). The average values for these ratios obtained over entire cone fields have been explained by the repose angle of loose granular material (i.e. scoria) controlling cone slopes. The observed variability in these ratios between individual cones has been attributed to the effect of erosional processes or contrasting eruptive conditions on cone morphometry. Using a GIS-based approach, high spatial resolution Digital Elevation Models and airphotos, two new geomorphometry datasets for cone fields at Mauna Kea (Hawaii, USA) and Lanzarote (Canary Islands, Spain) are extracted and analyzed here. The key observation in these datasets is the great variability in morphometric ratios, even for simple-shape and well-preserved cones. Simple analog experiments are presented to analyze factors influencing the morphometric ratios. The formation of a crater is simulated within an analog cone (i.e. a sand pile) by opening a drainage conduit at the cone base. Results from experiments show that variability in the morphometric ratios can be attributed to variations in the width, height and horizontal offset of the drainage point relative to the cone symmetry axis, to the dip of the underlying slope or to the influence of a small proportion of fine cohesive material. GIS analysis and analog experiments, together with specific examples of cones documented in the field, suggest that the morphometric ratios for well-preserved volcanic cones are controlled by a combination of 1) the intrinsic cone material properties, 2) time-dependent eruption conditions, 3) the local setting, and 4) the method used to estimate the cone height. Implications for interpreting cone morphometry solely as either an age or as an eruption condition indicator are highlighted.

Photoreceptors in a primitive mammal, the South American opossum, Didelphis marsupialis aurita: characterization with anti-opsin immunolabeling.

PubMed

Ahnelt, P K; Hokoç, J N; Röhlich, P

1995-01-01

The retinas of placental mammals appear to lack the large number and morphological diversity of cone subtypes found in diurnal reptiles. We have now studied the photoreceptor layer of a South American marsupial (Didelphis marsupialis aurita) by peanut agglutinin labeling of the cone sheath and by labeling of cone outer segments with monoclonal anti-visual pigment antibodies that have been proven to consistently label middle-to-long wavelength (COS-1) and short-wavelength (OS-2) cone subpopulations in placental mammals. Besides a dominant rod population (max. = 400,000/mm2) four subtypes of cones (max. = 3000/mm2) were identified. The outer segments of three cone subtypes were labeled by COS-1: a double cone with a principal cone containing a colorless oil droplet, a single cone with oil droplet, and another single cone. A second group of single cones lacking oil droplets was labeled by OS-2 antibody. The topography of these cone subtypes showed striking anisotropies. The COS-1 labeled single cones without oil droplets were found all over the retina and constituted the dominant population in the area centralis located in the temporal quadrant of the upper, tapetal hemisphere. The population of OS-2 labeled cones was also ubiquitous although slightly higher in the upper hemisphere (200/mm2). The COS-1 labeled cones bearing an oil droplet, including the principal member of double cones, were concentrated (800/mm2) in the inferior, non-tapetal half of the retina. The two spectral types of single cones resemble those of dichromatic photopic systems in most placental mammals. The additional set of COS-1 labeled cones is a distinct marsupial feature. The presence of oil droplets in this cone subpopulation, its absence in the area centralis, and the correlation with the non-tapetal inferior hemisphere suggest a functional specialization, possibly for mesopic conditions. Thus, sauropsid features have been retained but probably with a modified function.

UAS Collision Avoidance Algorithm that Minimizes the Impact on Route Surveillance

DTIC Science & Technology

2009-03-01

Appendix A: Collision Avoidance Algorithm/Virtual Cockpit Interface .......................124 Appendix B : Collision Cone Boundary Rates... b ) Split Cone (c) Multiple Intruders, Single and Split Cones [27] ........................................................ 27 3-3: Collision Cone...Approach in the Vertical Plane (a) Single Cone ( b ) Multiple Intruders, Single and Split Cone [27

Effect of Altered Retinal Cones/Opsins on Refractive Development under Monochromatic Lights in Guinea Pigs

PubMed Central

Zou, Leilei; Zhu, Xiaoyu; Liu, Rui; Ma, Fei; Yu, Manrong

2018-01-01

Purpose To analyze the changes of refraction and metabolism of the retinal cones under monochromatic lights in guinea pigs. Methods Sixty guinea pigs were randomly divided into a short-wavelength light (SL) group, a middle-wavelength light (ML) group, and a white light (WL) group. Refraction and axial length were measured before and after 10-week illumination. The densities of S-cones and M-cones were determined by retinal cone immunocytochemistry, and the expressions of S-opsins and M-opsins were determined by real-time PCR and Western blot. Results After 10-week illumination, the guinea pigs developed relative hyperopia in the SL group and relative myopia in the ML group. Compared with the WL group, the density of S-cones and S-opsins increased while M-cones and M-opsins decreased in the SL group (all, p < 0.05); conversely, the density of S-cones and S-opsins decreased while M-cones and M-opsins increased in the ML group (all, p < 0.05). Increased S-cones/opsins and decreased M-cones/opsins were induced by short-wavelength lights. Decreased S-cones/opsins and increased M-cones/opsins were induced by middle-wavelength lights. Conclusions Altered retinal cones/opsins induced by monochromatic lights might be involved in the refractive development in guinea pigs. PMID:29675275

Increased risk of chronic liver disease in patients with bipolar disorder: A population-based study.

PubMed

Hsu, Jer-Hwa; Chien, I-Chia; Lin, Ching-Heng

2016-01-01

This study aimed to investigate the prevalence and incidence of chronic liver disease in patients with bipolar disorder. We used a random sample of 766,427 subjects aged ≥18 years from the National Health Research Institute database in the year 2005. Subjects with at least one primary diagnosis of bipolar disorder in 2005 were identified. Patients with a primary or secondary diagnosis of chronic liver disease were also defined. We compared the prevalence and associated factors of chronic liver disease between patients with bipolar disorder and the general population in 2005. We also compared the incidence of chronic liver disease in patients with bipolar disorder and the general population from 2006 to 2010. The prevalence of chronic liver disease in patients with bipolar disorder (13.9%) was 2.68 times higher than that of the general population (5.8%) in 2005. The average annual incidence of chronic liver disease in patients with bipolar disorder from 2006 to 2010 was also higher than that of the general population (2.95% vs. 1.73%; risk ratio: 1.71; 95% confidence interval: 1.46-2.01). Patients with bipolar disorder had a significantly higher prevalence and incidence of chronic liver disease than those in the general population, and younger patients with bipolar disorder have a much higher prevalence and incidence than those in the general population. Male sex, second-generation antipsychotic or antidepressant use, and hyperlipidemia were associated factors for chronic liver disease in patients with bipolar disorder. Copyright © 2016 Elsevier Inc. All rights reserved.

Prevalence and correlates of bipolar disorders in patients with eating disorders.

PubMed

Tseng, Mei-Chih Meg; Chang, Chin-Hao; Chen, Kuan-Yu; Liao, Shih-Cheng; Chen, Hsi-Chung

2016-01-15

To investigate the prevalence and correlates of bipolar disorders in patients with eating disorders (EDs), and to examine differences in effects between major depressive disorder and bipolar disorder on these patients. Sequential attendees were invited to participate in a two-phase survey for EDs at the general psychiatric outpatient clinics. Patients diagnosed with EDs (n=288) and controls of comparable age, sex, and educational level (n=81) were invited to receive structured interviews for psychiatric co-morbidities, suicide risks, and functional level. All participants also completed several self-administered questionnaires assessing general and eating-related pathology and impulsivity. Characteristics were compared between the control, ED-only, ED with major depressive disorder, and ED with bipolar disorder groups. Patients with all ED subtypes had significantly higher rates of major depressive disorder (range, 41.3-66.7%) and bipolar disorder (range, 16.7-49.3%) than controls did. Compared to patients with only EDs, patients with comorbid bipolar disorder and those with comorbid major depressive disorder had significantly increased suicidality and functional impairments. Moreover, the group with comorbid bipolar disorder had increased risks of weight dysregulation, more impulsive behaviors, and higher rates of psychiatric comorbidities. Participants were selected in a tertiary center of a non-Western country and the sample size of individuals with bipolar disorder in some ED subtypes was small. Bipolar disorders were common in patients with EDs. Careful differentiation between bipolar disorder and major depressive disorder in patients with EDs may help predict associated psychopathology and provide accurate treatment. Copyright © 2015 Elsevier B.V. All rights reserved.

Differential brain network activity across mood states in bipolar disorder.

PubMed

Brady, Roscoe O; Tandon, Neeraj; Masters, Grace A; Margolis, Allison; Cohen, Bruce M; Keshavan, Matcheri; Öngür, Dost

2017-01-01

This study aimed to identify how the activity of large-scale brain networks differs between mood states in bipolar disorder. The authors measured spontaneous brain activity in subjects with bipolar disorder in mania and euthymia and compared these states to a healthy comparison population. 23 subjects with bipolar disorder type I in a manic episode, 24 euthymic bipolar I subjects, and 23 matched healthy comparison (HC) subjects underwent resting state fMRI scans. Using an existing parcellation of the whole brain, we measured functional connectivity between brain regions and identified significant differences between groups. In unbiased whole-brain analyses, functional connectivity between parietal, occipital, and frontal nodes within the dorsal attention network (DAN) were significantly greater in mania than euthymia or HC subjects. In the default mode network (DMN), connectivity between dorsal frontal nodes and the rest of the DMN differentiated both mood state and diagnosis. The bipolar groups were separate cohorts rather than subjects imaged longitudinally across mood states. Bipolar mood states are associated with highly significant alterations in connectivity in two large-scale brain networks. These same networks also differentiate bipolar mania and euthymia from a HC population. State related changes in DAN and DMN connectivity suggest a circuit based pathology underlying cognitive dysfunction as well as activity/reactivity in bipolar mania. Altered activities in neural networks may be biomarkers of bipolar disorder diagnosis and mood state that are accessible to neuromodulation and are promising novel targets for scientific investigation and possible clinical intervention. Copyright © 2016 Elsevier B.V. All rights reserved.

Clinical features of bipolar spectrum with binge eating behaviour.

PubMed

McElroy, Susan L; Crow, Scott; Blom, Thomas J; Cuellar-Barboza, Alfredo B; Prieto, Miguel L; Veldic, Marin; Winham, Stacey J; Bobo, William V; Geske, Jennifer; Seymour, Lisa R; Mori, Nicole; Bond, David J; Biernacka, Joanna M; Frye, Mark A

2016-09-01

To determine whether bipolar spectrum disorder with binge eating behavior (BE) is an important clinical sub-phenotype. Prevalence rates and correlates of different levels of BE were assessed in 1114 bipolar spectrum patients participating in a genetic biobank. BE and eating disorders (EDs) were assessed with the Eating Disorder Diagnostic Scale (EDDS). Psychiatric illness burden was evaluated with measures of suicidality, psychosis, mood instability, anxiety disorder comorbidity, and substance abuse comorbidity. Medical illness burden was evaluated with body mass index (BMI) and the Cumulative Index Rating Scale (CIRS). Thirty percent of patients had any BE and 27% had BE plus an ED diagnosis. Compared with bipolar spectrum patients without BE, bipolar spectrum patients with BE were younger and more likely to be female; had significantly higher levels of eating psychopathology, suicidality, mood instability, and anxiety disorder comorbidity; had a significantly higher mean BMI and a significantly higher rate of obesity; and had a significantly higher medical illness burden. Bipolar spectrum patients with BE but no ED diagnosis were more similar to bipolar spectrum patients without BE than to those with an ED. Nonetheless, the positive predictive value and specificity of BE predicting an ED was 0.90 and 0.96, respectively. As only two patients had co-occurring anorexia nervosa, these results may not generalize to bipolar spectrum patients with restricting EDs. Bipolar spectrum disorder with broadly-defined BE may not be as clinically relevant a sub-phenotype as bipolar spectrum disorder with an ED but may be an adequate proxy for the latter when phenotyping large samples of individuals. Copyright © 2016. Published by Elsevier B.V.

Infrared evaluation of the heat-sink bipolar diathermy dissection technique.

PubMed

Allan, J; Dusseldorp, J; Rabey, N G; Malata, C M; Goltsman, D; Phoon, A F

2015-08-01

The use of the bipolar diathermy dissection technique is widespread amongst surgeons performing flap perforator dissection and microvascular surgery. The 'heat-sink' modification uses a DeBakey forcep as a heat sinking interposition between the bipolar tip and the main (vascular or flap) pedicle aiming to protect it from the thermal effects of the bipolar diathermy. This study examines the thermal effects of bipolar cautery upon the microvasculature and investigates the efficacy of heat sinking as a thermally protective technique in microsurgical dissection. A chicken thigh microsurgical training model was used to examine the effects of bipolar cautery. The effects of bipolar were examined using high definition, real-time infrared thermographic imaging (FLIR Systems) and temperature quantitatively assessed at various distances away from the point of bipolar cautery. Comparison was made using the heat sink technique to determine if it conferred a thermoprotective effect compared to the standard technique without heat sink. Using paired t-test analysis (SPSS) the heat sink modification of the bipolar dissection technique was found to have a highly statistically significant effect (P < 0.000000001) in reducing the conductive temperature along the vascular pedicle. This protective effect kept temperatures comparable to controls. Bipolar cautery is an extremely safe method of electrosurgery, however when its use is required within 3 mm of important vascular architecture, the heat-sink method is a viable and easy technique to prevent thermal spread and limit potential coagulopathic changes. Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Does recent mania affect response to antidepressants in bipolar disorder? A re-analysis of STEP-BD data.

PubMed

Mousavi, Zahra; Johnson, Sheri; Li, Descartes

2018-08-15

One previous study suggested that the presence of a manic episode before bipolar depression is related to worse response to antidepressants. To examine this effect in a larger sample, we used data from the large, multi-site STEP-BD study. We hypothesized that among persons treated with antidepressants for bipolar depression, manic or mixed episodes before depression onset (as compared to euthymia) would predict lower rate of recovery, more sustained depressive symptoms and higher rate of switching into mania/hypomania after antidepressant treatment of bipolar depression. 320 participants were available for analyses (140 male) diagnosed with bipolar I, bipolar II, cyclothymia, bipolar disorder not otherwise specified, or schizoaffective disorder bipolar subtype. Patients were randomly assigned to 3 treatment randomization strata (placebo, bupropion, and paroxetine) as adjuncts to mood stabilizers. Analyses were conducted to examine the effect of episode status before the depressive episode on the degree of change in depressive symptoms at 3 and 6 months, the likelihood of depression recovery and the likelihood of anti-depressant induced switching. Presence of a manic episode before depression in patients with bipolar disorder did not significantly predict response to antidepressants. The study was limited by a high rate of attrition, and consideration of only two antidepressant medications. Our findings are in agreement with other past studies suggesting that mania and depression may operate separately for those with bipolar disorder, with differential predictors of the onset and offset of mania versus depression. Future directions may consider vulnerability for these episodes separately. Copyright © 2018 Elsevier B.V. All rights reserved.

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

PubMed

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.

Variability in human cone topography assessed by adaptive optics scanning laser ophthalmoscopy

PubMed Central

Zhang, Tianjiao; Godara, Pooja; Blanco, Ernesto R.; Griffin, Russell L; Wang, Xiaolin; Curcio, Christine A.; Zhang, Yuhua

2015-01-01

Purpose To assess between- and within-individual variability of macular cone topography in the eyes of young adults. Design Observational case series. Methods Cone photoreceptors in 40 eyes of 20 subjects aged 19–29 years with normal maculae were imaged using a research adaptive optics scanning laser ophthalmoscope. Refractive errors ranged from −3.0 D to 0.63 D and differed by <0.50 D in fellow eyes. Cone density was assessed on a two-dimensional sampling grid over the central 2.4 mm × 2.4 mm. Between-individual variability was evaluated by coefficient of variation (CV). Within-individual variability was quantified by maximum difference and root-mean-square (RMS). Cones were cumulated over increasing eccentricity. Results Peak densities of foveal cones are 168,162 ± 23,529 cones/mm2 (mean ± SD) (CV = 0.14). The number of cones within the cone-dominated foveola (0.8–0.9 mm diameter) is 38,311 ± 2,319 (CV = 0.06). The RMS cone density difference between fellow eyes is 6.78%, and the maximum difference is 23.6%. Mixed model statistical analysis found no difference in the association between eccentricity and cone density in the superior/nasal (p=0.8503), superior/temporal (p=0.1551), inferior/nasal (p=0.8609), and inferior/temporal (p=0.6662) quadrants of fellow eyes. Conclusions New instrumentation imaged the smallest foveal cones, thus allowing accurate assignment of foveal centers and assessment of variability in macular cone density in a large sample of eyes. Though cone densities vary significantly in the fovea, the total number of foveolar cones are very similar both between- and within-subjects. Thus, the total number of foveolar cones may be an important measure of cone degeneration and loss. PMID:25935100

Elevated levels of kynurenic acid in the cerebrospinal fluid of patients with bipolar disorder

PubMed Central

Olsson, Sara K.; Samuelsson, Martin; Saetre, Peter; Lindström, Leif; Jönsson, Erik G.; Nordin, Conny; Engberg, Göran; Erhardt, Sophie; Landén, Mikael

2010-01-01

Background Patients with schizophrenia show elevated brain levels of the neuroactive tryptophan metabolite kynurenic acid (KYNA). This astrocyte-derived mediator acts as a neuroprotectant and modulates sensory gating and cognitive function. We measured the levels of KYNA in the cerebrospinal fluid (CSF) of patients with bipolar disorder and healthy volunteers to investigate the putative involvement of KYNA in bipolar disorder. Methods We obtained CSF by lumbar puncture from 23 healthy men and 31 euthymic men with bipolar disorder. We analyzed the samples using high-performance liquid chromatography. Results Patients with bipolar disorder had increased levels of KYNA in their CSF compared with healthy volunteers (1.71 nM, standard error of the mean [SEM] 0.13 v. 1.13 nM, SEM 0.09; p = 0.002. The levels of KYNA were positively correlated with age among bipolar patients but not healthy volunteers. Limitations The influence of ongoing drug treatment among patients cannot be ruled out. We conducted our study during the euthymic phase of the disease. Conclusion Brain KYNA levels are increased in euthymic men with bipolar disorder. In addition, KYNA levels increased with age in these patients. These findings indicate shared mechanisms between bipolar disorder and schizophrenia. Elevated levels of brain KYNA may provide further insight to the pathophysiology and progression of bipolar disorder. PMID:20420770

Glial cell-derived neurotrophic factor gene polymorpisms affect severity and functionality of bipolar disorder.

PubMed

Safari, Roghaiyeh; Tunca, Zeliha; Özerdem, Ayşegül; Ceylan, Deniz; Yalçın, Yaprak; Sakizli, Meral

2017-01-01

Glial cell-derived neurotrophic factor and other neurotrophins have important role in the development of mental disorders. Here, we aimed to assess the effects of Single nucleotide polymorphisms at potentially regulated regions of GDNF on severity and functionality of bipolar disorder and GDNF serum levels in bipolar disorder patients and healthy volunteers. Severity and functionality of bipolar disorder were evaluated using the Clinical Global Impression and Global Assessment of Functioning scales in sixty-six bipolar disorder patients. The GDNF serum levels obtained from bipolar disorder patients and healthy volunteers who had been already reported SNPs information by our group. GAF scales were lower and GDNF serum levels were higher in Bipolar disorder patients with T/A genotype at 5:37812784 and 5:37812782 compared to patients with T/T genotype. There were significant difference in severity and functionality scores, but not in GDNF serum levels, between patients with G/G and G/A genotype of rs62360370 G > A SNP.rs2075680 C > A and rs79669773 T > C SNPs had no effect on bipolar disorder severity and functionality scores and GDNF serum levels. The results suggest that some SNPs of GDNF have potential association with severity and functionality of bipolar disorder. In addition, except two SNPs, none of GDNF SNPs had association with GDNF serum levels.

Racial disparities in bipolar disorder treatment and research: a call to action.

PubMed

Akinhanmi, Margaret O; Biernacka, Joanna M; Strakowski, Stephen M; McElroy, Susan L; Balls Berry, Joyce E; Merikangas, Kathleen R; Assari, Shervin; McInnis, Melvin G; Schulze, Thomas G; LeBoyer, Marion; Tamminga, Carol; Patten, Christi; Frye, Mark A

2018-03-12

Health disparities between individuals of African and European ancestry are well documented. The disparities in bipolar disorder may be driven by racial bias superimposed on established factors contributing to misdiagnosis, including: evolving empirically based diagnostic criteria (International Classification of Diseases [ICD], Research Diagnostic Criteria [RDC] and Diagnostic and Statistical Manual [DSM]), multiple symptom domains (i.e. mania, depression and psychosis), and multimodal medical and additional psychiatric comorbidity. For this paper, we reviewed the phenomenological differences between bipolar individuals of African and European ancestry in the context of diagnostic criteria and clinical factors that may contribute to a potential racial bias. Published data show that bipolar persons of African ancestry, compared with bipolar persons of non-African ancestry, are more often misdiagnosed with a disease other than bipolar disorder (i.e. schizophrenia). Additionally, studies show that there are disparities in recruiting patients of African ancestry to participate in important genomic studies. This gap in biological research in this underrepresented minority may represent a missed opportunity to address potential racial differences in the risk and course of bipolar illness. A concerted effort by the research community to increase inclusion of diverse persons in studies of bipolar disorder through community engagement may facilitate fully addressing these diagnostic and treatment disparities in bipolar individuals of African ancestry. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.

The Loudness Dependence of Auditory Evoked Potentials (LDAEP) in individuals at risk for developing bipolar disorders and schizophrenia.

PubMed

Hagenmuller, Florence; Heekeren, Karsten; Meier, Magali; Theodoridou, Anastasia; Walitza, Susanne; Haker, Helene; Rössler, Wulf; Kawohl, Wolfram

2016-02-01

The Loudness Dependence of Auditory Evoked Potentials (LDAEP) is considered as an indicator of central serotonergic activity. Alteration of serotonergic neurotransmission was reported in bipolar disorders and schizophrenia. In line with previous reports on clinically manifest disorders, we expected a weaker LDAEP in subjects at risk for bipolar disorders and schizophrenia compared to healthy controls. We analyzed LDAEP of individuals at risk for developing bipolar disorders (n=27), with high-risk status (n=74) and ultra-high-risk status for schizophrenia (n=86) and healthy controls (n=47). The LDAEP did not differ between subjects at risk for schizophrenia or bipolar disorders and controls. Among subjects without medication (n=122), the at-risk-bipolar group showed a trend towards a weaker LDAEP than both the high-risk and the ultra-high-risk groups for schizophrenia. The LDAEP did not appear as a vulnerability marker for schizophrenia or bipolar disorders. This suggests that an altered LDAEP may not be measurable until the onset of clinically manifest disorder. However, the hypothesis that pathogenic mechanisms leading to bipolar disorders may differ from those leading to schizophrenia is supported. This is the first study investigating LDAEP in a population at risk for bipolar disorders. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Theory of mind and functionality in bipolar patients with symptomatic remission.

PubMed

Barrera, Angeles; Vázquez, Gustavo; Tannenhaus, Lucila; Lolich, María; Herbst, Luis

2013-01-01

Functional deficits are commonly observed in bipolar disorder after symptomatic remission. Social cognition deficits have also been reported, which could contribute to dysfunction in patients with bipolar disorder in remission. Twelve bipolar disorder patients in symptomatic remission (7 patients with bipolar disorder type I and 5 with bipolar disorder type II) and 12 healthy controls completed the Reading the Mind in the Eyes Test and the Faux Pas Test to evaluate theory of mind (ToM). Both groups also completed the Functional Assessment Short Test (FAST). The performance of the bipolar patients in the cognitive component of ToM was below normal, although the difference between the control group was not statistically significant (P=.078), with a trend to a worse performance associated with a higher number of depressive episodes (P=.082). There were no statistically significant differences between groups for the emotional component of ToM. Global functionality was significantly lower in bipolar patients compared to the control group (P=.001). Significant differences were also observed between both groups in five of the six dimensions of functionality assessed. No significant correlation was found between functionality and theory of mind. Bipolar patients in symptomatic remission exhibit impairments in several areas of functioning. Cognitive ToM appears more affected than emotional ToM. Deficits in ToM were not related to functional impairment. Copyright © 2012 SEP y SEPB. Published by Elsevier Espana. All rights reserved.

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

PubMed

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.

[Differences in Subjective Experience Between Unipolar and Bipolar Depression].

PubMed

Fierro, Marco; Bustos, Andrés; Molina, Carlos

2016-01-01

It is important to make distinction between bipolar and unipolar depression because treatment and prognosis are different. Since the diagnosis of the two conditions is purely clinical, find symptomatic differences is useful. Find differences in subjective experience (first person) between unipolar and bipolar depression. Phenomenological-oriented qualitative exploratory study of 12 patients (7 with bipolar depression and 5 with unipolar depression, 3 men and 9 women). We used a semi-structured interview based on Examination of Anomalous Self-Experience (EASE). The predominant mood in bipolar depression is emotional dampening, in unipolar is sadness. The bodily experience in bipolar is of a heavy, tired body; an element that inserts between the desires of acting and performing actions and becomes an obstacle to the movement. In unipolar is of a body that feels more comfortable with the stillness than activity, like laziness of everyday life. Cognition and the stream of consciousness: in bipolar depression, compared with unipolar, thinking is slower, as if to overcome obstacles in their course. There are more difficult to understand what is heard or read. Future perspective: in bipolar depression, hopelessness is stronger and broader than in unipolar, as if the very possibility of hope was lost. Qualitative differences in predominant mood, bodily experience, cognition and future perspective were found between bipolar and unipolar depression. Copyright © 2015 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

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

PubMed

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.

Mindfulness-based Cognitive Therapy (MBCT) in bipolar disorder: Preliminary evaluation of immediate effects on between-episode functioning

PubMed Central

Williams, J.M.G.; Alatiq, Y.; Crane, C.; Barnhofer, T.; Fennell, M.J.V.; Duggan, D.S.; Hepburn, S.; Goodwin, G.M.

2008-01-01

Background Bipolar disorder is highly recurrent and rates of comorbidity are high. Studies have pointed to anxiety comorbidity as one factor associated with risk of suicide attempts and poor overall outcome. This study aimed to explore the feasibility and potential benefits of a new psychological treatment (Mindfulness-based Cognitive Therapy: MBCT) for people with bipolar disorder focusing on between-episode anxiety and depressive symptoms. Methods The study used data from a pilot randomized trial of MBCT for people with bipolar disorder in remission, focusing on between-episode anxiety and depressive symptoms. Immediate effects of MBCT versus waitlist on levels of anxiety and depression were compared between unipolar and bipolar participants. Results The results suggest that MBCT led to improved immediate outcomes in terms of anxiety which were specific to the bipolar group. Both bipolar and unipolar participants allocated to MBCT showed reductions in residual depressive symptoms relative to those allocated to the waitlist condition. Limitations Analyses were based on a small sample, limiting power. Additionally the study recruited participants with suicidal ideation or behaviour so the findings cannot immediately be generalized to individuals without these symptoms. Conclusions The study, although preliminary, suggests an immediate effect of MBCT on anxiety and depressive symptoms among bipolar participants with suicidal ideation or behaviour, and indicates that further research into the use of MBCT with bipolar patients may be warranted. PMID:17884176

Changes in mood stabilizer prescription patterns in bipolar disorder.

PubMed

Karanti, Alina; Kardell, Mathias; Lundberg, Ulrika; Landén, Mikael

2016-05-01

Lithium is a first line treatment option in bipolar disorder, but several alternative treatments have been introduced in recent years, such as antiepileptic and atypical antipsychotic drugs. Little is known about how this has changed the prescription patterns. We investigated possible changes in the use of mood stabilizers and antidepressants in Sweden during 2007-2013. Data was collected from Swedish registers: the National Quality Assurance Register for bipolar disorder (BipoläR), the Prescribed Drug Register, and the Patient Register. Logistic regression models with drug use as outcomes were used to adjust for confounding factors such as sex, age, year of registration, and subtypes of bipolar disorder. In both bipolar subtypes, lithium use decreased steadily during the study period, while the use of lamotrigine and quetiapine increased. The use of valproate decreased in bipolar II disorder and the use of olanzapine decreased among women. The use of antidepressant remained principally unchanged but increased somewhat in bipolar I disorder. We only report data from 2007 as the coverage of BipoläR prior to 2007 was too low to allow for reliable analyses. Significant changes in the prescription of drugs in the treatment of bipolar disorder have occurred in recent years in Sweden. Further studies are needed to clarify whether these changes alter the outcome in bipolar disorder. Copyright © 2016 Elsevier B.V. All rights reserved.

Deficits in social cognition and response flexibility in pediatric bipolar disorder.

PubMed

McClure, Erin B; Treland, Julia E; Snow, Joseph; Schmajuk, Mariana; Dickstein, Daniel P; Towbin, Kenneth E; Charney, Dennis S; Pine, Daniel S; Leibenluft, Ellen

2005-09-01

Little is known about neuropsychological and social-cognitive function in patients with pediatric bipolar disorder. Identification of specific deficits and strengths that characterize pediatric bipolar disorder would facilitate advances in diagnosis, treatment, and research on pathophysiology. The purpose of this study was to test the hypothesis that youths with bipolar disorder would perform more poorly than matched healthy comparison subjects on measures of social cognition, motor inhibition, and response flexibility. Forty outpatients with pediatric bipolar disorder and 22 comparison subjects (no differences in age, gender, and IQ) completed measures of social cognition (the pragmatic judgment subtest of the Comprehensive Assessment of Spoken Language, facial expression recognition subtests of the Diagnostic Analysis of Nonverbal Accuracy Scale, the oral expression subtest of the Test of Language Competence), inhibition and response flexibility (stop and stop-change tasks), and motor inhibition (continuous performance tasks). Pediatric bipolar disorder patients performed more poorly than comparison subjects on social-cognitive measures (pragmatic judgment of language, facial expression recognition) and on a task requiring response flexibility. These deficits were present in euthymic patients. Differences between patients and comparison subjects could not be attributed to comorbid attention deficit hyperactivity disorder. Findings of impaired social cognition and response flexibility in youths with pediatric bipolar disorder suggest continuity between pediatric bipolar disorder and adult bipolar disorder. These findings provide a foundation for neurocognitive research designed to identify the neural mechanisms underlying these deficits.

Improving Treatment Adherence in Bipolar Disorder: A Review of Current Psychosocial Treatment Efficacy and Recommendations for Future Treatment Development

ERIC Educational Resources Information Center

Gaudiano, Brandon A.; Weinstock, Lauren M.; Miller, Ivan W.

2008-01-01

Treatment adherence is a frequent problem in bipolar disorder, with research showing that more than 60% of bipolar patients are at least partially nonadherent to medications. Treatment nonadherence is consistently predictive of a number of negative outcomes in bipolar samples, and the discontinuation of mood stabilizers places these patients at…

Clinical, Demographic, and Familial Correlates of Bipolar Spectrum Disorders among Offspring of Parents with Bipolar Disorder

ERIC Educational Resources Information Center

Goldstein, Benjamin I.; Shamseddeen, Wael; Axelson, David A.; Kalas, Cathy; Monk, Kelly; Brent, David A.; Kupfer, David J.; Birmaher, Boris

2010-01-01

Objective: Despite increased risk, most offspring of parents with bipolar disorder (BP) do not manifest BP. The identification of risk factors for BP among offspring could improve preventive and treatment strategies. We examined this topic in the Pittsburgh Bipolar Offspring Study (BIOS). Method: Subjects included 388 offspring, ages 7-17 years,…

Child Behavior Checklist Profiles of Children and Adolescents with and at High Risk for Developing Bipolar Disorder

ERIC Educational Resources Information Center

Giles, Lisa L.; DelBello, Melissa P.; Stanford, Kevin E.; Strakowski, Stephen M.

2007-01-01

In order to recognize behavioral patterns in children and adolescents at risk for developing bipolar disorder, this study examined Child Behavior Checklist (CBCL) profiles of bipolar offspring both with (BD group) and without ("at-risk" or AR group) bipolar disorder themselves. The BD youth had three CBCL subscale T scores greater than…

Bipolar Disorder in Children

PubMed Central

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

Bipolar affective disorder and psychoeducation.

PubMed

Prasko, Jan; Ociskova, Marie; Kamaradova, Dana; Sedlackova, Zuzana; Cerna, Monika; Mainerova, Barbora; Sandoval, Aneta

2013-01-01

Bipolar affective disorder runs a natural course of frequent relapses and recurrences. Despite significant strides in the pharmacological treatment of bipolar disorder, most bipolar patients cannot be treated only by drugs. The limitations of using medication alone in symptomatic, relapse prevention, and satisfaction/quality of life terms have long prompted interest in wider forms of management. One of the promising way how to enhance remission seems to be combination of pharmacotherapy and psychoeducation. Studies were identified through PUBMED, Web of Science and Scopus databases as well as existing reviews. The search terms included "bipolar disorder", "psychoeducation", "psychotherapy", "psychosocial treatment", "family therapy", "individual therapy", "group therapy", and "psychoeducation". The search was performed by repeated use of the words in different combinations with no language or time limitations. This article is a review with conclusions concerned with psychoeducation in bipolar disorder. Randomized controlled trials of cognitive behavioral therapy, interpersonal and social rhythm therapy, individual, group and family psychoeducation show that these approaches augment stabilizing effect of pharmacotherapy. Patients and their families should be educated about bipolar disorder, triggers, warning signs, mood relapse, suicidal ideation, and the effectiveness of early intervention to reduce complications. Psychosocial approaches are important therapeutic strategies for reducing relapse and rehospitalization in bipolar disorder.

Bipolar electrocautery: A rodent model of Sunderland third-degree nerve injury.

PubMed

Moradzadeh, Arash; Brenner, Michael J; Whitlock, Elizabeth L; Tong, Alice Y; Luciano, Janina P; Hunter, Daniel A; Myckatyn, Terence M; Mackinnon, Susan E

2010-01-01

To determine the Sunderland classification of a bipolar electrocautery injury. Twenty-two rats received crush (a reproducible Sunderland second-degree injury) or bipolar electrocautery injury and were evaluated for functional, histomorphometric, and immunohistochemical recovery at 21 or 42 days. Animal experiments were performed between July 3 and December 12, 2007. Axonal regeneration and end plate reinnervation were evaluated in double transgenic cyan fluorescent protein-conjugated Thy1 and green fluorescent protein-conjugated S100 mice. Compared with crush injury, bipolar electrocautery injury caused greater disruption of myelin and neurofilament architecture at the injury site and decreased nerve fiber counts and percentage of neural tissue distal to the injury (P =.007). Complete functional recovery was seen after crush but not bipolar electrocautery injury. Serial live imaging demonstrated axonal regeneration at week 1 after crush and at week 3 after bipolar electrocautery injury. Qualitative assessment of motor end plate reinnervation at 42 days demonstrated complete neuromuscular end plate reinnervation in the crush group and only limited reinnervation in the bipolar electrocautery group. Bipolar electrocautery injury in a rodent model resulted in a Sunderland third-degree injury, characterized by gradual, incomplete recovery without intervention.

Thin co-radial bipolar leads: technology and clinical performance.

PubMed

Fahraeus, T; Israel, C W; Wöllenstein, M

2001-09-01

While bipolar leads offer advantages such as better sensing performance than unipolar leads, their use has been limited by a larger lead diameter and reports about a high failure rate of several bipolar lead models. This has led to the development of thin bipolar leads using a special technology which aims at improving lead safety. Leads with monofilar thin conductors (drawn filled tube) which are individually coated with a very resistant material (ETFE) have been developed. Using a co-radial instead of co-axial bipolar conductor design, the lead diameter could be reduced to 4.5 F compared to 6-7 F of conventional bipolar leads. Bench testing demonstrated a significant improvement of this lead technology with respect to degradation of insulation material by biochemically reactive solutions. Also mechanical characteristics such as resistance to tearing forces and compression showed a high lead durability. From our own experience, co-radial bipolar leads show a favorable electrical performance with the exception of a relatively low pacing impedance. Also during long-term follow-up, the rate of lead failure was very low. These findings are corroborated by other clinical studies which also demonstrated good handling characteristics of thin bipolar leads during implantation.

Prevention of Bipolar Disorder in At-Risk Children: Theoretical Assumptions and Empirical Foundations

PubMed Central

Miklowitz, David J.; Chang, Kiki D.

2007-01-01

This article examines how bipolar symptoms emerge during development, and the potential role of psychosocial and pharmacological interventions in the prevention of the onset of the disorder. Early signs of bipolarity can be observed among children of bipolar parents and often take the form of subsyndromal presentations (e.g., mood lability, episodic elation or irritability, depression, inattention, and psychosocial impairment). However, many of these early presentations are diagnostically nonspecific. The few studies that have followed at-risk youth into adulthood find developmental discontinuities from childhood to adulthood. Biological markers (e.g., amygdalar volume) may ultimately increase our accuracy in identifying children who later develop bipolar I disorder, but few such markers have been identified. Stress, in the form of childhood adversity or highly conflictual families, is not a diagnostically-specific causal agent but does place genetically and biologically vulnerable individuals at risk for a more pernicious course of illness. A preventative family-focused treatment for children with (a) at least one first-degree relative with bipolar disorder, and (b) subsyndromal signs of bipolar disorder, is described. This model attempts to address the multiple interactions of psychosocial and biological risk factors in the onset and course of bipolar disorder. PMID:18606036

Relationship between suicidality and impulsivity in bipolar I disorder: a diffusion tensor imaging study

PubMed Central

Mahon, Katie; Burdick, Katherine E; Wu, Jinghui; Ardekani, Babak A; Szeszko, Philip R

2012-01-01

Background Impulsivity is characteristic of individuals with bipolar disorder and may be a contributing factor to the high rate of suicide in patients with this disorder. Although white matter abnormalities have been implicated in the pathophysiology of bipolar disorder, their relationship to impulsivity and suicidality in this disorder has not been well-investigated. Methods Diffusion tensor imaging scans were acquired in 14 bipolar disorder patients with a prior suicide attempt, 15 bipolar disorder patients with no prior suicide attempt, and 15 healthy volunteers. Bipolar disorder patients received clinical assessments including measures of impulsivity, depression, mania, and anxiety. Images were processed using the Tract-Based Spatial Statistics method in the FSL software package. Results Bipolar disorder patients with a prior suicide attempt had lower fractional anisotropy (FA) within the left orbital frontal white matter (p < 0.05, corrected) and higher overall impulsivity compared to patients without a previous suicide attempt. Among patients with a prior suicide attempt, FA in the orbital frontal white matter region correlated inversely with motor impulsivity. Conclusions Abnormal orbital frontal white matter may play a role in impulsive and suicidal behavior among patients with bipolar disorder. PMID:22329475

Intraoperative dislocation of the trial bipolar cup into the pelvis during bipolar hip arthroplasty - A case report.

PubMed

Miyake, Takahito; Kanda, Akio; Morohashi, Itaru; Obayashi, Osamu; Mogami, Atsuhiko; Kaneko, Kazuo

2017-06-01

Bipolar hip arthroplasty is a good option for treating femoral neck fractures, although some contraindications have been indicated. We report a case of intraoperative dislocation of the trial bipolar cup into the pelvis during bipolar hip arthroplasty. A 74-year-old woman underwent bipolar hip arthroplasty for a femoral neck fracture (AO31-B2). She was placed in a lateral decubitus position, and a direct lateral approach was used. During intraoperative trial reduction, the trial bipolar cup became disengaged and dislocated into the anterior space of hip joint. Several attempts to retrieve it failed. The permanent femoral component was inserted, and the wound was closed. The patient was repositioned supine to allow an ilioinguinal approach, and the component was easily removed. She had an uneventful, good recovery. Several cases of intraoperative dislocation of the femoral trial head during total hip arthroplasty have been reported, this is the first report of dislocation of a bipolar trial cup. A previous report described difficulty retrieving a trial cup. We easily removed our trial cup using another approach. It is vital to plan systematically for this frustrating complication.

Response styles, bipolar risk, and mood in students: The Behaviours Checklist.

PubMed

Fisk, Claire; Dodd, Alyson L; Collins, Alan

2015-12-01

An Integrative Cognitive Model of mood swings and bipolar disorder proposes that extreme positive and negative appraisals about internal states trigger ascent and descent behaviours, contributing to the onset and maintenance of mood swings. This study investigated the reliability and validity of a new inventory, the Behaviours Checklist (BC), by measuring associations with appraisals, response styles to positive and negative affect, bipolar risk, mania, and depression. Correlational analogue study. Students (N = 134) completed the BC alongside measures of appraisals, response styles to positive and negative mood, mania, depression, and hypomanic personality (bipolar risk). The BC was of adequate reliability and showed good validity. Ascent behaviours and appraisals predicted bipolar risk, whereas descent behaviours and appraisals were associated with depression. Appraisals, ascent, and descent behaviours may play an important role in the development and maintenance of mood swings. Limitations and research recommendations are outlined. Extreme positive and negative appraisals of internal states, and subsequent behavioural responses (ascent and descent behaviours), are associated with bipolar risk and bipolar mood symptoms in a student sample. These processes are involved with mood dysregulation in clinical populations as well as bipolar risk in students, with implications for mood management. © 2015 The British Psychological Society.

Suicide attempts and clinical features of bipolar patients.

PubMed

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.

Pregnancy and bipolar disorder: a systematic review.

PubMed

Sharma, Verinder; Pope, Carley J

2012-11-01

The postpartum period is generally considered a time of heightened vulnerability to bipolar disorder; however, there is controversy about the effect of pregnancy on the course of bipolar disorder. This article reviews the literature on the relationship between pregnancy and bipolar disorder and suggests areas for future research. Three electronic databases, MEDLINE (1966-2010), PsycINFO (1840-2010), and EMBASE, were searched on April 30, 2010, using the following keywords: pregnancy, bipolar disorder, manic depressive disorder, suicide, hospitalization, pharmacotherapy, and psychotherapy. The reference lists of articles identified were also searched. All relevant papers published in English were included. A total of 70 articles were identified and included in the review. Evidence from studies using nonclinical samples, some retrospective studies, and studies on psychiatric hospitalization rates is suggestive of a positive effect of pregnancy on bipolar disorder; however, recent studies conducted at tertiary care facilities have reported high rates of recurrence following discontinuation of mood stabilizers. Understanding the relationship between pregnancy and bipolar disorder has implications for perinatal treatment and etiologic understanding of the disorder. Research is urgently needed to estimate the prevalence of bipolar disorder during pregnancy, using both clinical and nonclinical samples. © Copyright 2012 Physicians Postgraduate Press, Inc.

Broadening the diagnosis of bipolar disorder: benefits vs. risks

PubMed Central

STRAKOWSKI, STEPHEN M.; FLECK, DAVID E.; MAJ, MARIO

2011-01-01

There is considerable debate over whether bipolar and related disorders that share common signs and symptoms, but are currently defined as distinct clinical entities in DSM-IV and ICD-10, may be better characterized as falling within a more broadly defined “bipolar spectrum”. With a spectrum view in mind, the possibility of broadening the diagnosis of bipolar disorder has been proposed. This paper discusses some of the rationale for an expanded diagnostic scheme from both clinical and research perspectives in light of potential drawbacks. The ultimate goal of broadening the diagnosis of bipolar disorder is to help identify a common etiopathogenesis for these conditions to better guide treatment. To help achieve this goal, bipolar researchers have increasingly expanded their patient populations to identify objective biological or endophenotypic markers that transcend phenomenological observation. Although this approach has and will likely continue to produce beneficial results, the upcoming DSM-IV and ICD-10 revisions will place increasing scrutiny on psychiatry’s diagnostic classification systems and pressure to re-evaluate our conceptions of bipolar disorder. However, until research findings can provide consistent and converging evidence as to the validity of a broader diagnostic conception, clinical expansion to a dimensional bipolar spectrum should be considered with caution. PMID:21991268

Treatment of bipolar disorders during pregnancy: maternal and fetal safety and challenges

PubMed Central

Epstein, Richard A; Moore, Katherine M; Bobo, William V

2015-01-01

Treating pregnant women with bipolar disorder is among the most challenging clinical endeavors. Patients and clinicians are faced with difficult choices at every turn, and no approach is without risk. Stopping effective pharmacotherapy during pregnancy exposes the patient and her baby to potential harms related to bipolar relapses and residual mood symptom-related dysfunction. Continuing effective pharmacotherapy during pregnancy may prevent these occurrences for many; however, some of the most effective pharmacotherapies (such as valproate) have been associated with the occurrence of congenital malformations or other adverse neonatal effects in offspring. Very little is known about the reproductive safety profile and clinical effectiveness of atypical antipsychotic drugs when used to treat bipolar disorder during pregnancy. In this paper, we provide a clinically focused review of the available information on potential maternal and fetal risks of untreated or undertreated maternal bipolar disorder during pregnancy, the effectiveness of interventions for bipolar disorder management during pregnancy, and potential obstetric, fetal, and neonatal risks associated with core foundational pharmacotherapies for bipolar disorder. PMID:25565896

The Diagnosis and Management of Bipolar I and II Disorders: Clinical Practice Update.

PubMed

Bobo, William V

2017-10-01

Bipolar disorders, including bipolar I disorder (BP-I) and bipolar II disorder (BP-II), are common, potentially disabling, and, in some cases, life-threatening conditions. Bipolar disorders are characterized by alternating episodes of mania or hypomania and depression, or mixtures of manic and depressive features. Bipolar disorders present many diagnostic and therapeutic challenges for busy clinicians. Adequate management of bipolar disorders requires pharmacotherapy and psychosocial interventions targeted to the specific phases of illness. Effective treatments are available for each illness phase, but mood episode relapses and incomplete responses to treatment are common, especially for the depressive phase. Mood symptoms, psychosocial functioning, and suicide risk must, therefore, be continually reevaluated, and, when necessary, the plan of care must be adjusted during long-term treatment. Many patients will require additional treatment of comorbid psychiatric and substance use disorders and management of a variety of commonly co-occurring chronic general medical conditions. Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

PHARMAC and treatment of bipolar depression--the limits of utilitarianism.

PubMed

Ellis, Pete; Mulder, Roger; Porter, Richard

2006-03-31

Bipolar disorder affects 1.6% of the population. The majority of the burden of illness for people with bipolar disorder is due to depression. Suicide rates for people with bipolar disorder are 15 times higher than in the general population, and the majority of these deaths occur during depressive episodes. More effective prevention of such depressive episodes is important. Lamotrigine is an anticonvulsant and a mood stabiliser that is more effective at preventing depressive relapses than most other mood stabilising drugs. Its use for this purpose has been recommended by English language treatment guidelines since 2002. Lamotrigine is approved for use in the prophylaxis of depression in bipolar disorder and for epilepsy. PHARMAC subsidises its use in treatment-resistant epilepsy (subject to a 'special authority' application) but not in bipolar disorder. The New Zealand Mental Health Strategy and the imminent New Zealand Suicide Strategy identify reducing suicide as a key goal. Among other initiatives, this requires effective treatment of bipolar depression, yet a treatment likely to support this is not currently subsidised.