The North-South Asymmetry of the Heliospheric Current Sheet: Results of an MHD Simulation

NASA Technical Reports Server (NTRS)

Usmanov, Arcadi V.; Goldstein, Melvyn L.

2013-01-01

A displacement of the heliospheric current sheet (HCS) south of the helioequator by approx.10deg was proposed by Simpson et al. (1996) as a possible explanation of the north-south asymmetry in the galactic cosmic rays observed by Ulysses during its first fast transit in 1994-1995. The idea was not supported by magnetic field measurements on Ulysses and, on this ground, was dismissed by Simpson et al. (1996). In addition, Erdos & Balogh (1998) argued that any north-south symmetry was unlikely as there should be flux balance between the magnetic sectors of opposite polarity. Nonetheless, many in the scientific community have accepted the original suggestion of Simpson et al. (1996) that a displacement of the HCS was responsible for the cosmic ray asymmetry. In this paper, using a magnetohydrodynamic model of the solar corona and solar wind that includes both dipole and quadrupole magnetic source terms, we show that a north-south asymmetry of the magnetic field on the Sun does not give rise to a displacement of the HCS. The lack of displacement of the HCS results from a latitudinal redistribution of magnetic flux near the Sun where the plasma beta much < 1. The latitudinal redistribution is a direct consequence of the magnetic field gradient between pole and equator. Near the Sun, the latitudinal gradient in magnetic field generates meridional flows directed equatorward that tend to relax the gradient in the magnetic field (to make it more latitude-independent) as heliocentric distance increases. If there is an asymmetry between north and south magnetic field strength then the meridional flows are also asymmetric (i.e., stronger in the hemisphere of stronger magnetic field). Because the magnetic fluxes (positive and negative) in the hemispheres must be equal, the redistribution shifts the HCS into balance by approx. 16 R(solar mass). At larger distances, where the magnetic field is relatively weak (beta much > 1), the HCS can be displaced if there is a difference in total pressure between the hemispheres.

Bashful ballerina unveiled: Multipole analysis of the coronal magnetic field

NASA Astrophysics Data System (ADS)

Virtanen, I.; Mursula, K.

2012-12-01

Heliospheric current sheet (HCS) is the continuum of the coronal magnetic equator, dividing the heliospheric magnetic field (HMF) into two sectors (polarities). Because of its wavy structure, the HCS is often called the ballerina skirt. Several studies have proven that the HCS is southward shifted during about three years in the solar declining phase. This persistent phenomenon, called the bashful ballerina, has been verified by geomagnetic indices since 1930s, by OMNI data base since 1960s, by the WSO PFSS model since mid-1970s and by the Ulysses probe measurements during the fast latitude scans in 1994-1995 and 2007. We study here the Wilcox Solar Observatory measurements of the photospheric magnetic field and the PFSS extrapolation of the coronal magnetic field. We show that the quadrupole moment of the photospheric magnetic field, which is important for the HCS asymmetry (bashful ballerina), mainly arises from the difference between northern and southern polar field strengths. According to the WSO data the minimum time quadrupole is mainly due to the difference between the highest northern and southern latitude bins. Related studies imply that the southward shift of the HCS is related to the delayed development of southern coronal holes. We also discuss the suggested connection of the HCS asymmetry to sunspot hemispheric asymmetry.

Fact Sheet: Revisions to the Occupational Safety and Health Administration Hazard Communication Standards (HCS)

EPA Pesticide Factsheets

On March 26, 2012, Occupational Safety and Health Administration (OSHA) modified its HCS to conform to the United Nations’ (UN) Globally Harmonized System of Classification and Labeling of Chemicals (GHS), to improve consistency and quality of information.

Structured Slow Solar Wind Variability: Streamer-blob Flux Ropes and Torsional Alfvén Waves

NASA Astrophysics Data System (ADS)

Higginson, A. K.; Lynch, B. J.

2018-05-01

The slow solar wind exhibits strong variability on timescales from minutes to days, likely related to magnetic reconnection processes in the extended solar corona. Higginson et al. presented a numerical magnetohydrodynamic simulation that showed interchange magnetic reconnection is ubiquitous and most likely responsible for releasing much of the slow solar wind, in particular along topological features known as the Separatrix-Web (S-Web). Here, we continue our analysis, focusing on two specific aspects of structured slow solar wind variability. The first type is present in the slow solar wind found near the heliospheric current sheet (HCS), and the second we predict should be present everywhere S-Web slow solar wind is observed. For the first type, we examine the evolution of three-dimensional magnetic flux ropes formed at the top of the helmet streamer belt by reconnection in the HCS. For the second, we examine the simulated remote and in situ signatures of the large-scale torsional Alfvén wave (TAW), which propagates along an S-Web arc to high latitudes. We describe the similarities and differences between the reconnection-generated flux ropes in the HCS, which resemble the well-known “streamer blob” observations, and the similarly structured TAW. We discuss the implications of our results for the complexity of the HCS and surrounding plasma sheet and the potential for particle acceleration, as well as the interchange reconnection scenarios that may generate TAWs in the solar corona. We discuss predictions from our simulation results for the dynamic slow solar wind in the extended corona and inner heliosphere.

Global Network of Slow Solar Wind

NASA Technical Reports Server (NTRS)

Crooker, N. U.; Antiochos, S. K.; Zhao, X.; Neugebauer, M.

2012-01-01

The streamer belt region surrounding the heliospheric current sheet (HCS) is generally treated as the primary or sole source of the slow solar wind. Synoptic maps of solar wind speed predicted by the Wang-Sheeley-Arge model during selected periods of solar cycle 23, however, show many areas of slow wind displaced from the streamer belt. These areas commonly have the form of an arc that is connected to the streamer belt at both ends. The arcs mark the boundaries between fields emanating from different coronal holes of the same polarity and thus trace the paths of belts of pseudostreamers, i.e., unipolar streamers that form over double arcades and lack current sheets. The arc pattern is consistent with the predicted topological mapping of the narrow open corridor or singular separator line that must connect the holes and, thus, consistent with the separatrix-web model of the slow solar wind. Near solar maximum, pseudostreamer belts stray far from the HCS-associated streamer belt and, together with it, form a global-wide web of slow wind. Recognition of pseudostreamer belts as prominent sources of slow wind provides a new template for understanding solar wind stream structure, especially near solar maximum.

SMALL-SCALE MAGNETIC ISLANDS IN THE SOLAR WIND AND THEIR ROLE IN PARTICLE ACCELERATION. II. PARTICLE ENERGIZATION INSIDE MAGNETICALLY CONFINED CAVITIES

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

Khabarova, Olga V.; Zank, Gary P.; Li, Gang

2016-08-20

We explore the role of heliospheric magnetic field configurations and conditions that favor the generation and confinement of small-scale magnetic islands associated with atypical energetic particle events (AEPEs) in the solar wind. Some AEPEs do not align with standard particle acceleration mechanisms, such as flare-related or simple diffusive shock acceleration processes related to interplanetary coronal mass ejections (ICMEs) and corotating interaction regions (CIRs). As we have shown recently, energetic particle flux enhancements may well originate locally and can be explained by particle acceleration in regions filled with small-scale magnetic islands with a typical width of ∼0.01 au or less, whichmore » is often observed near the heliospheric current sheet (HCS). The particle energization is a consequence of magnetic reconnection-related processes in islands experiencing either merging or contraction, observed, for example, in HCS ripples. Here we provide more observations that support the idea and the theory of particle energization produced by small-scale-flux-rope dynamics (Zank et al. and Le Roux et al.). If the particles are pre-accelerated to keV energies via classical mechanisms, they may be additionally accelerated up to 1–1.5 MeV inside magnetically confined cavities of various origins. The magnetic cavities, formed by current sheets, may occur at the interface of different streams such as CIRs and ICMEs or ICMEs and coronal hole flows. They may also form during the HCS interaction with interplanetary shocks (ISs) or CIRs/ICMEs. Particle acceleration inside magnetic cavities may explain puzzling AEPEs occurring far beyond ISs, within ICMEs, before approaching CIRs as well as between CIRs.« less

The evolution of 1 AU equatorial solar wind and its association with the morphology of the heliospheric current sheet from solar cycles 23 to 24

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

Zhao, L.; Landi, E.; Zurbuchen, T. H.

2014-09-20

The solar wind can be categorized into three types based on its 'freeze-in' temperature (T {sub freeze-in}) in the coronal source: low T {sub freeze-in} wind mostly from coronal holes, high T {sub freeze-in} wind mostly from regions outside of coronal holes, including streamers (helmet streamer and pseudostreamer), active regions, etc., and transient interplanetary coronal mass ejections (ICMEs) usually possessing the hottest T {sub freeze-in}. The global distribution of these three types of wind has been investigated by examining the most effective T {sub freeze-in} indicator, the O{sup 7+}/O{sup 6+} ratio, as measured by the Solar Wind Ion Composition Spectrometermore » on board the Advanced Composition Explorer (ACE) during 1998-2008 by Zhao et al. In this study, we extend the previous investigation to 2011 June, covering the unusual solar minimum between solar cycles 23 and 24 (2007-2010) and the beginning of solar cycle 24. We find that during the entire solar cycle, from the ascending phase of cycle 23 in 1998 to the ascending phase of cycle 24 in 2011, the average fractions of the low O{sup 7+}/O{sup 6+} ratio (LOR) wind, the high O{sup 7+}/O{sup 6+} ratio (HOR) wind, and ICMEs at 1 AU are 50.3%, 39.4%, and 10.3%, respectively; the contributions of the three types of wind evolve with time in very different ways. In addition, we compare the evolution of the HOR wind with two heliospheric current sheet (HCS) parameters, which indicate the latitudinal standard deviation (SD) and the slope (SL) of the HCS on the synoptic Carrington maps at 2.5 solar radii surface. We find that the fraction of HOR wind correlates with SD and SL very well (slightly better with SL than with SD), especially after 2005. This result verifies the link between the production of HOR wind and the morphology of the HCS, implying that at least one of the major sources of the HOR wind must be associated with the HCS.« less

Three-Dimensional Evolution of Flux-Rope CMEs and Its Relation to the Local Orientation of the Heliospheric Current Sheet

NASA Astrophysics Data System (ADS)

Isavnin, A.; Vourlidas, A.; Kilpua, E. K. J.

2014-06-01

Flux ropes ejected from the Sun may change their geometrical orientation during their evolution, which directly affects their geoeffectiveness. Therefore, it is crucial to understand how solar flux ropes evolve in the heliosphere to improve our space-weather forecasting tools. We present a follow-up study of the concepts described by Isavnin, Vourlidas, and Kilpua ( Solar Phys. 284, 203, 2013). We analyze 14 coronal mass ejections (CMEs), with clear flux-rope signatures, observed during the decay of Solar Cycle 23 and rise of Solar Cycle 24. First, we estimate initial orientations of the flux ropes at the origin using extreme-ultraviolet observations of post-eruption arcades and/or eruptive prominences. Then we reconstruct multi-viewpoint coronagraph observations of the CMEs from ≈ 2 to 30 R⊙ with a three-dimensional geometric representation of a flux rope to determine their geometrical parameters. Finally, we propagate the flux ropes from ≈ 30 R⊙ to 1 AU through MHD-simulated background solar wind while using in-situ measurements at 1 AU of the associated magnetic cloud as a constraint for the propagation technique. This methodology allows us to estimate the flux-rope orientation all the way from the Sun to 1 AU. We find that while the flux-ropes' deflection occurs predominantly below 30 R⊙, a significant amount of deflection and rotation happens between 30 R⊙ and 1 AU. We compare the flux-rope orientation to the local orientation of the heliospheric current sheet (HCS). We find that slow flux ropes tend to align with the streams of slow solar wind in the inner heliosphere. During the solar-cycle minimum the slow solar-wind channel as well as the HCS usually occupy the area in the vicinity of the solar equatorial plane, which in the past led researchers to the hypothesis that flux ropes align with the HCS. Our results show that exceptions from this rule are explained by interaction with the Parker-spiraled background magnetic field, which dominates over the magnetic interaction with the HCS in the inner heliosphere at least during solar-minimum conditions.

Formation of Heliospheric Arcs of Slow Solar Wind

NASA Technical Reports Server (NTRS)

Higginson, A. K.; Antiochos, S. K.; Devore, C. R.; Wyper, P. F.; Zurbuchen, T. H.

2017-01-01

A major challenge in solar and heliospheric physics is understanding the origin and nature of the so-called slow solar wind. The Sun's atmosphere is divided into magnetically open regions, known as coronal holes, where the plasma streams out freely and fills the solar system, and closed regions, where the plasma is confined to coronal loops. The boundary between these regions extends outward as the heliospheric current sheet (HCS). Measurements of plasma composition strongly imply that much of the slow wind consists of plasma from the closed corona that escapes onto open field lines, presumably by field-line opening or by interchange reconnection. Both of these processes are expected to release closed-field plasma into the solar wind within and immediately adjacent to the HCS. Mysteriously, however, slow wind with closed-field plasma composition is often observed in situ far from the HCS. We use high-resolution, three-dimensional, magnetohydrodynamic simulations to calculate the dynamics of a coronal hole with a geometry that includes a narrow corridor flanked by closed field and is driven by supergranule-like flows at the coronal-hole boundary. These dynamics produce giant arcs of closed-field plasma that originate at the open-closed boundary in the corona, but extend far from the HCS and span tens of degrees in latitude and longitude at Earth. We conclude that such structures can account for the long-puzzling slow-wind observations.

Formation of Heliospheric Arcs of Slow Solar Wind

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

Higginson, A. K.; Zurbuchen, T. H.; Antiochos, S. K.

A major challenge in solar and heliospheric physics is understanding the origin and nature of the so-called slow solar wind. The Sun’s atmosphere is divided into magnetically open regions, known as coronal holes, where the plasma streams out freely and fills the solar system, and closed regions, where the plasma is confined to coronal loops. The boundary between these regions extends outward as the heliospheric current sheet (HCS). Measurements of plasma composition strongly imply that much of the slow wind consists of plasma from the closed corona that escapes onto open field lines, presumably by field-line opening or by interchangemore » reconnection. Both of these processes are expected to release closed-field plasma into the solar wind within and immediately adjacent to the HCS. Mysteriously, however, slow wind with closed-field plasma composition is often observed in situ far from the HCS. We use high-resolution, three-dimensional, magnetohydrodynamic simulations to calculate the dynamics of a coronal hole with a geometry that includes a narrow corridor flanked by closed field and is driven by supergranule-like flows at the coronal-hole boundary. These dynamics produce giant arcs of closed-field plasma that originate at the open-closed boundary in the corona, but extend far from the HCS and span tens of degrees in latitude and longitude at Earth. We conclude that such structures can account for the long-puzzling slow-wind observations.« less

Investigation of Periodic Nuclear Decay Data with Spectral Analysis Techniques

NASA Astrophysics Data System (ADS)

Javorsek, D.; Sturrock, P.; Buncher, J.; Fischbach, E.; Gruenwald, T.; Hoft, A.; Horan, T.; Jenkins, J.; Kerford, J.; Lee, R.; Mattes, J.; Morris, D.; Mudry, R.; Newport, J.; Petrelli, M.; Silver, M.; Stewart, C.; Terry, B.; Willenberg, H.

2009-12-01

We provide the results from a spectral analysis of nuclear decay experiments displaying unexplained periodic fluctuations. The analyzed data was from 56Mn decay reported by the Children's Nutrition Research Center in Houston, 32Si decay reported by an experiment performed at the Brookhaven National Laboratory, and 226Ra decay reported by an experiment performed at the Physikalisch-Technische-Bundesanstalt in Germany. All three data sets possess the same primary frequency mode consisting of an annual period. Additionally a spectral comparison of the local ambient temperature, atmospheric pressure, relative humidity, Earth-Sun distance, and the plasma speed and latitude of the heliospheric current sheet (HCS) was performed. Following analysis of these six possible causal factors, their reciprocals, and their linear combinations, a possible link between nuclear decay rate fluctuations and the linear combination of the HCS latitude and 1/R motivates searching for a possible mechanism with such properties.

Following the geomagnetic activity: events on September and October (1999)

NASA Astrophysics Data System (ADS)

Blanco, J. J.; Hidalgo, M. A.; Rodríguez-Pacheco, J.; Medina, J.; Sequeiros, J.; Nieves-Chinchilla, T.

2006-12-01

On 21-22 October 1999 a very intense geomagnetic storm (DST index: -237 nT) was detected. This event was associated with a High Speed Stream (HSS) and an interplanetary coronal mass ejection. Before and after this event, the interplanetary magnetic field showed an inversion probably associated with Heliospheric Current Sheet (HCS) crossings. One month before (21-22 September) a strong geomagnetic storm (DST index: -164 nT) was detected and the solar wind conditions were similar to those observed in October, i. e. magnetic cloud, HSS and HCS crossings. Nevertheless, the October event was stronger than the September one. We have compared both events trying to clarify what caused the difference between them. This work has been supported by the Spanish Comisión Internacional de Ciencia y Tecnología (CICYT), grant ESP2005-07290-C02-01 and ESP2006-08459 and Madrid Autonomous Community / University of Alcala grant CAM-UAH 2005/007.

Ulysses Data Analysis: Magnetic Topology of Heliospheric Structures

NASA Technical Reports Server (NTRS)

Crooker, Nancy

2001-01-01

In this final technical report on research funded by a NASA grant, a project overview is given by way of summaries on nine published papers. Research has included: 1) Using suprathermal electron data to study heliospheric magnetic structures; 2) Analysis of magnetic clouds, coronal mass ejections (CME), and the heliospheric current sheet (HCS); 3) Analysis of the corotating interaction region (CIR) which develop from interactions between solar wind streams of different velocities; 4) Use of Ulysses data in the interpretation of heliospheric events and phenomena.

Hemispheric asymmetry in coronal hole evolution: Cause of the bashful ballerina?

NASA Astrophysics Data System (ADS)

Mursula, K.; Tlatov, A.; Virtanen, I.

2012-12-01

The magnetic hemisphere prevalent in the solar northern hemisphere has been shown to cover a larger area than in the south for about three years in the declining phase of several solar cycles. Correspondingly, the average field intensity is weaker in the northern hemisphere and the heliospheric current sheet (HCS) is shifted southward at these times. This phenomenon, now called the bashful ballerina, has been verified using several databases and methods, including the in situ observations of the heliospheric magnetic field (HMF) at 1 AU by the OMNI data base, at about 2 AU by the Ulysses probe, and at different radial distances by the Voyager 1 and 2 and Pioneer 10 and 11 probes. The Ulysses observations show that the mean southward shift of the HCS was about 2 degrees in the declining phase of both cycle 22 and cycle 23, although the polar strengths were very different between the two cycles. The HMF observations by the Voyager and Pioneer probes show a very consistent structure of HMF sectors and HCS location in the entire heliosphere, and even beyond the termination shock. Moreover, they suggest a systematic difference in the development of northern and southern polar coronal holes. While the northern coronal holes developed very systematically during all the four solar minima since mid-1970s, the evolution of southern coronal holes was less systematic and delayed with respect to the northern hemisphere. This delay in the evolution of southern coronal holes leads to a larger extent of northern coronal holes and a southward shift of the heliospheric current sheet (the bashful ballerina phenomenon) for a few years in the declining phase of the solar cycle. Here we study direct observations of solar coronal holes and verify this difference in the evolution of coronal holes between the two solar hemispheres, which explains the bashful ballerina phenomenon.

A Numerical Study of Forbush Decreases with a 3D Cosmic-Ray Modulation Model Based on an SDE Approach

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

Luo, Xi; Feng, Xueshang; Potgieter, Marius S.

Based on the reduced diffusion mechanism for producing Forbush decreases (Fds) in the heliosphere, we constructed a three-dimensional (3D) diffusion barrier, and by incorporating it into a stochastic differential equation (SDE) based time-dependent, cosmic-ray transport model, a 3D numerical model for simulating Fds is built and applied to a period of relatively quiet solar activity. This SDE model generally corroborates previous Fd simulations concerning the effects of the solar magnetic polarity, the tilt angle of the heliospheric current sheet (HCS), and cosmic-ray particle energy. Because the modulation processes in this 3D model are multi-directional, the barrier’s geometrical features affect themore » intensity profiles of Fds differently. We find that both the latitudinal and longitudinal extent of the barrier have relatively fewer effects on these profiles than its radial extent and the level of decreased diffusion inside the disturbance. We find, with the 3D approach, that the HCS rotational motion causes the relative location from the observation point to the HCS to vary, so that a periodic pattern appears in the cosmic-ray intensity at the observing location. Correspondingly, the magnitude and recovery time of an Fd change, and the recovering intensity profile contains oscillation as well. Investigating the Fd magnitude variation with heliocentric radial distance, we find that the magnitude decreases overall and, additionally, that the Fd magnitude exhibits an oscillating pattern as the radial distance increases, which coincides well with the wavy profile of the HCS under quiet solar modulation conditions.« less

Ick Ciliary Kinase Is Essential for Planar Cell Polarity Formation in Inner Ear Hair Cells and Hearing Function.

PubMed

Okamoto, Shio; Chaya, Taro; Omori, Yoshihiro; Kuwahara, Ryusuke; Kubo, Shun; Sakaguchi, Hirofumi; Furukawa, Takahisa

2017-02-22

Cellular asymmetries play crucial roles in development and organ function. The planar cell polarity (PCP) signaling pathway is involved in the establishment of cellular asymmetry within the plane of a cell sheet. Inner ear sensory hair cells (HCs), which have several rows of staircase-like stereocilia and one kinocilium located at the vertex of the stereocilia protruding from the apical surface of each HC, exhibit a typical form of PCP. Although connections between cilia and PCP signaling in vertebrate development have been reported, their precise nature is not well understood. During inner ear development, several ciliary proteins are known to play a role in PCP formation. In the current study, we investigated a functional role for intestinal cell kinase (Ick), which regulates intraflagellar transport (IFT) at the tip of cilia, in the mouse inner ear. A lack of Ick in the developing inner ear resulted in PCP defects in the cochlea, including misorientation or misshaping of stereocilia and aberrant localization of the kinocilium and basal body in the apical and middle turns, leading to auditory dysfunction. We also observed abnormal ciliary localization of Ift88 in both HCs and supporting cells. Together, our results show that Ick ciliary kinase is essential for PCP formation in inner ear HCs, suggesting that ciliary transport regulation is important for PCP signaling. SIGNIFICANCE STATEMENT The cochlea in the inner ear is the hearing organ. Planar cell polarity (PCP) in hair cells (HCs) in the cochlea is essential for mechanotransduction and refers to the asymmetric structure consisting of stereociliary bundles and the kinocilium on the apical surface of the cell body. We reported previously that a ciliary kinase, Ick, regulates intraflagellar transport (IFT). Here, we found that loss of Ick leads to abnormal localization of the IFT component in kinocilia, PCP defects in HCs, and hearing dysfunction. Our study defines the association of ciliary transport regulation with PCP formation in HCs and hearing function. Copyright © 2017 the authors 0270-6474/17/372073-13$15.00/0.

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

Guo, X.; Florinski, V.

We present a new model that couples galactic cosmic-ray (GCR) propagation with magnetic turbulence transport and the MHD background evolution in the heliosphere. The model is applied to the problem of the formation of corotating interaction regions (CIRs) during the last solar minimum from the period between 2007 and 2009. The numerical model simultaneously calculates the large-scale supersonic solar wind properties and its small-scale turbulent content from 0.3 au to the termination shock. Cosmic rays are then transported through the background, and thus computed, with diffusion coefficients derived from the solar wind turbulent properties, using a stochastic Parker approach. Ourmore » results demonstrate that GCR variations depend on the ratio of diffusion coefficients in the fast and slow solar winds. Stream interfaces inside the CIRs always lead to depressions of the GCR intensity. On the other hand, heliospheric current sheet (HCS) crossings do not appreciably affect GCR intensities in the model, which is consistent with the two observations under quiet solar wind conditions. Therefore, variations in diffusion coefficients associated with CIR stream interfaces are more important for GCR propagation than the drift effects of the HCS during a negative solar minimum.« less

Lessons Learned from 10 Years of STEREO Solar Wind Observations

NASA Astrophysics Data System (ADS)

Jian, L. K.; Russell, C. T.; Luhmann, J. G.; Galvin, A. B.

2017-12-01

We have conducted long-term observations of large-scale solar wind structures since the launch of STEREO spacecraft, specifically interplanetary CMEs (ICMEs), slow-to-fast stream interaction regions (SIRs), and interplanetary shocks. In combination with our previous observations of the same solar wind structures in 1995-2009 using Wind/ACE data and the same identification criteria, we have first studied the solar cycle variations of these structures, especially for the same phases of solar cycles 23 and 24. Attributing the shocks to the interplanetary drivers, we have statistically compared the shocks driven by ICMEs and SIRs, and explained the shocks without a clear local driver. In addition, using the longitudinal and latitudinal separations between the twin spacecraft, we have investigated the recurrence and variability of ICMEs and SIRs, and gained the critical implications for the proposed L5 mission. At last, we have associated the heliospheric current sheet (HCS) crossings with the ICMEs and SIRs, and compared the properties of SIRs with and without HCS crossings, which correspond to the helmet streamers and pseudostreamers, respectively. The findings are important constraints on the theories of slow wind origin.

Pre-vascularization Enhances Therapeutic Effects of Human Mesenchymal Stem Cell Sheets in Full Thickness Skin Wound Repair.

PubMed

Chen, Lei; Xing, Qi; Zhai, Qiyi; Tahtinen, Mitchell; Zhou, Fei; Chen, Lili; Xu, Yingbin; Qi, Shaohai; Zhao, Feng

2017-01-01

Split thickness skin graft (STSG) implantation is one of the standard therapies for full thickness wound repair when full thickness autologous skin grafts (FTG) or skin flap transplants are inapplicable. Combined transplantation of STSG with dermal substitute could enhance its therapeutic effects but the results remain unsatisfactory due to insufficient blood supply at early stages, which causes graft necrosis and fibrosis. Human mesenchymal stem cell (hMSC) sheets are capable of accelerating the wound healing process. We hypothesized that pre-vascularized hMSC sheets would further improve regeneration by providing more versatile angiogenic factors and pre-formed microvessels. In this work, in vitro cultured hMSC cell sheets (HCS) and pre-vascularized hMSC cell sheets (PHCS) were implanted in a rat full thickness skin wound model covered with an autologous STSG. Results demonstrated that the HCS and the PHCS implantations significantly reduced skin contraction and improved cosmetic appearance relative to the STSG control group. The PHCS group experienced the least hemorrhage and necrosis, and lowest inflammatory cell infiltration. It also induced the highest neovascularization in early stages, which established a robust blood micro-circulation to support grafts survival and tissue regeneration. Moreover, the PHCS grafts preserved the largest amount of skin appendages, including hair follicles and sebaceous glands, and developed the smallest epidermal thickness. The superior therapeutic effects seen in PHCS groups were attributed to the elevated presence of growth factors and cytokines in the pre-vascularized cell sheet, which exerted a beneficial paracrine signaling during wound repair. Hence, the strategy of combining STSG with PHCS implantation appears to be a promising approach in regenerative treatment of full thickness skin wounds.

Encore of the Bashful ballerina in solar cycle 23

NASA Astrophysics Data System (ADS)

Mursula, K.; Virtanen, I. I.

2009-04-01

The rotation averaged location of the heliospheric current sheet has been found to be shifted systematically southward for about three years in the late declining to minimum phase of the solar cycle. This behaviour, called by the concept of the Bashful ballerina, has earlier been shown to be valid at least during the active solar cycle of the last century since the late 1920s. Recently, Zhao et al have analysed the WSO observations and conclude that there is no southward coning in HCS or north-south difference in the heliospheric magnetic field during the late declining phase of solar cycle 23. In disagreement with these results, we find that there is a similar but smaller southward shift of the HCS and dominance of the northern field area as in all previous solar cycles. The present smaller asymmetry is in agreement with an earlier observation based on long-term geomagnetic activity that solar hemispheric asymmetry is larger during highly active solar cycles. Moreover, we connect the smallness of shift to the structure of the solar magnetic field with an exceptionally large tilt. We also discuss the cause of the differences between the two approaches reaching different conclusions.

Construction of a human corneal stromal equivalent with non-transfected human corneal stromal cells and acellular porcine corneal stromata.

PubMed

Diao, Jin-Mei; Pang, Xin; Qiu, Yue; Miao, Ying; Yu, Miao-Miao; Fan, Ting-Jun

2015-03-01

A tissue-engineered human corneal stroma (TE-HCS) has been developed as a promising equivalent to the native corneal stroma for replacement therapy. However, there is still a crucial need to improve the current approaches to render the TE-HCS equivalent more favorable for clinical applications. At the present study, we constructed a TE-HCS by incubating non-transfected human corneal stromal (HCS) cells in an acellular porcine corneal stromata (aPCS) scaffold in 20% fetal bovine serum supplemented DMEM/F12 (1:1) medium at 37 °C with 5% CO2in vitro. After 3 days of incubation, the constructed TE-HCS had a suitable tensile strength for transplantation, and a transparency that is comparable to native cornea. The TE-HCS had a normal histological structure which contained regularly aligned collagen fibers and differentiated HCS cells with positive expression of marker and functional proteins, mimicking a native HCS. After transplantation into rabbit models, the TE-HCS reconstructed normal corneal stroma in vivo and function well in maintaining corneal clarity and thickness, indicating that the completely biological TE-HCS could be used as a HCS equivalent. The constructed TE-HCS has promising potentials in regenerative medicine and treatment of diseases caused by corneal stromal disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

Coronal and heliospheric magnetic flux circulation and its relation to open solar flux evolution

PubMed Central

Owens, Mathew J.; Imber, Suzanne M.; James, Matthew K.; Bunce, Emma J.; Yeoman, Timothy K.

2017-01-01

Abstract Solar cycle 24 is notable for three features that can be found in previous cycles but which have been unusually prominent: (1) sunspot activity was considerably greater in the northern/southern hemisphere during the rising/declining phase; (2) accumulation of open solar flux (OSF) during the rising phase was modest, but rapid in the early declining phase; (3) the heliospheric current sheet (HCS) tilt showed large fluctuations. We show that these features had a major influence on the progression of the cycle. All flux emergence causes a rise then a fall in OSF, but only OSF with foot points in opposing hemispheres progresses the solar cycle via the evolution of the polar fields. Emergence in one hemisphere, or symmetric emergence without some form of foot point exchange across the heliographic equator, causes poleward migrating fields of both polarities in one or both (respectively) hemispheres which temporarily enhance OSF but do not advance the polar field cycle. The heliospheric field observed near Mercury and Earth reflects the asymmetries in emergence. Using magnetograms, we find evidence that the poleward magnetic flux transport (of both polarities) is modulated by the HCS tilt, revealing an effect on OSF loss rate. The declining phase rise in OSF was caused by strong emergence in the southern hemisphere with an anomalously low HCS tilt. This implies the recent fall in the southern polar field will be sustained and that the peak OSF has limited implications for the polar field at the next sunspot minimum and hence for the amplitude of cycle 25. PMID:28781930

Coronal and heliospheric magnetic flux circulation and its relation to open solar flux evolution.

PubMed

Lockwood, Mike; Owens, Mathew J; Imber, Suzanne M; James, Matthew K; Bunce, Emma J; Yeoman, Timothy K

2017-06-01

Solar cycle 24 is notable for three features that can be found in previous cycles but which have been unusually prominent: (1) sunspot activity was considerably greater in the northern/southern hemisphere during the rising/declining phase; (2) accumulation of open solar flux (OSF) during the rising phase was modest, but rapid in the early declining phase; (3) the heliospheric current sheet (HCS) tilt showed large fluctuations. We show that these features had a major influence on the progression of the cycle. All flux emergence causes a rise then a fall in OSF, but only OSF with foot points in opposing hemispheres progresses the solar cycle via the evolution of the polar fields. Emergence in one hemisphere, or symmetric emergence without some form of foot point exchange across the heliographic equator, causes poleward migrating fields of both polarities in one or both (respectively) hemispheres which temporarily enhance OSF but do not advance the polar field cycle. The heliospheric field observed near Mercury and Earth reflects the asymmetries in emergence. Using magnetograms, we find evidence that the poleward magnetic flux transport (of both polarities) is modulated by the HCS tilt, revealing an effect on OSF loss rate. The declining phase rise in OSF was caused by strong emergence in the southern hemisphere with an anomalously low HCS tilt. This implies the recent fall in the southern polar field will be sustained and that the peak OSF has limited implications for the polar field at the next sunspot minimum and hence for the amplitude of cycle 25.

The wide skirt of the bashful ballerina: Hemispheric asymmetry of the heliospheric magnetic field in the inner and outer heliosphere

NASA Astrophysics Data System (ADS)

Mursula, K.; Virtanen, I. I.

2012-08-01

We reanalyze the observations of the heliospheric magnetic field (HMF) made by the Pioneer 10 and 11 and Voyager 1 and 2 heliospheric probes since 1972, and calculate the HMF sector occurrence ratios and tangential component strengths in the different regions of the heliosphere. Observations at the distant probes and at 1 AU show a very consistent picture of the HMF sector structure in the entire heliosphere, and even beyond the termination shock. HMF observations by the probes also support the southward shift of the heliospheric current sheet (the bashful ballerina phenomenon), which is observed earlier at 1-2 AU by the Ulysses probe and Earth-orbiting satellites, and verify the HCS shift over a wide range of radial distances until the distant heliosphere. Pioneer 11 and Voyager 1 show that the development of northern polar coronal holes was very systematic and active during all the four solar minima since mid-1970s, while Voyager 2 observations show a less systematic and delayed development of southern coronal holes in 1980s, 1990s and 2000s. This delay in the evolution of southern coronal holes with respect to the rapid and systematic evolution of northern coronal holes leads to a larger extent of northern coronal holes and the southward shift of the HCS for a few years in the late declining phase of each solar cycle. Although evidence for the connection between the different evolution of polar coronal holes and the bashful ballerina phenomenon is obtained here only for three solar cycles, this may be a common pattern for solar coronal hole evolution since the southward shift of the HCS has occurred at least since solar cycle 16.

The role of volcanic aerosols and relativistic electrons in modulating winter storm vorticity

NASA Astrophysics Data System (ADS)

Tinsley, Brian A.; Zhou, Limin; Liu, Weiping

2012-09-01

Small changes in the vorticity of winter storms, responding to solar wind variations, are found in winters from 1957 to 2011, and are greater for winters with higher levels of stratospheric volcanic aerosols. Using 1993-2011 data, the response of the vorticity area index (VAI) is shown to be of larger amplitude when the days of minima in the relativistic electron flux (REF) precipitating from the radiation belts are used, instead of heliospheric current sheet (HCS) crossings, as key days in superposed epoch analyses. The HCS crossings mostly occur within a few days of the REF minima. The VAI is an objective measure of the area of high cyclonic vorticity, and for the present work is derived from ERA-40 and ERA-Interim reanalyses of global meteorological data. The VAI dependencies on the stratospheric aerosol content (SAC) and the REF are consistent with a model in which the ionosphere-earth current density (Jz) affects cloud microphysics. One of the ways in which Jz is modulated is by changes in stratospheric column resistance (S), which is increased by stratospheric aerosols. Because S is in series with the tropospheric column resistance (T), Jz modulation by REF requires that S be not negligible with respect to T. So the Jz modulation and the VAI response appear when the SAC is very high, or the REF reductions (which also increase S) are very deep, and when the product of the SAC and the reciprocal of the REF exceeds a threshold value dependent on T.

Anomalous and Galactic Cosmic Ray Intensities at 1 AU During the Approach to the Cycle 24/25 Solar Minimum and Throughout the Last 20 Years

NASA Astrophysics Data System (ADS)

Leske, R. A.; Cummings, A. C.; Mewaldt, R. A.; Cohen, C.; Stone, E. C.; Wiedenbeck, M. E.

2017-12-01

Anomalous cosmic ray (ACR) intensities at 1 AU generally track galactic cosmic ray (GCR) intensities, but with differences between solar polarity cycles: at high rigidities, GCRs reach higher peak intensities during A<0 cycles, while ACRs have been higher at A>0 solar minima. At present, during the approach to an A>0 solar minimum, ACR oxygen above 8 MeV/nucleon as measured by the Advanced Composition Explorer (ACE) has already reached the peak intensities seen during the 2009 A<0 solar minimum, but is still 40% below the levels seen in 1997 during the last A>0 minimum. The GCR iron intensity at 300 MeV/nucleon, on the other hand, is presently comparable to that in 1997 but remains 10% below its record-setting 2009 value. Drift effects play an important role in the modulation of both ACRs and GCRs. Positively charged ions drift inward along the heliospheric current sheet (HCS) during A<0 cycles and their intensities are thus sensitive to the HCS tilt angle, which remained high for much of the last solar cycle. We have previously shown that both ACR and GCR intensities were significantly higher for a given HCS tilt angle during the 2000-2012 A<0 cycle than they were during the prior (1980-1990) A<0 cycle, and this trend appears to be continuing into the new A>0 cycle. But while GCR intensities in 2009 reached the highest levels recorded during the last 50 years, ACR intensities were only similar to those in the 1980s A<0 minimum. Factors such as a weaker interplanetary magnetic field, perhaps with a reduction in the ACR source strength or greater sensitivity of ACRs than GCRs to the HCS tilt angle, may account for the difference in their modulation behavior.We present 20 years of ACR and GCR intensity data acquired by ACE throughout two solar cycles, with emphasis on recent observations, and discuss possible reasons for the differences in the relative behavior of ACRs and GCRs in the different solar cycles.

Sustained and transient calcium currents in horizontal cells of the white bass retina.

PubMed

Sullivan, J M; Lasater, E M

1992-01-01

Calcium currents were recorded from cultured horizontal cells (HCs) isolated from adult white bass retinas, using the whole-cell patch-clamp technique. Ca2+ currents were enhanced using 10 mM extracellular Ca2+, while Na+ and K+ currents were pharmacologically suppressed. Two components of the Ca2+ current, one transient, the other sustained, were found. The large transient component of the Ca2+ current, which has not been seen before in HCs, is similar, but not identical, to the T-type Ca2+ current described previously in a variety of preparations. The sustained component of the Ca2+ current is similar, but not identical, to the L-type current described in other preparations. FTX, a factor isolated from the venom of the funnel-web spider, Agelenopsis aperta, preferentially and irreversibly blocks the sustained component of the Ca2+ current at very dilute concentrations. The sustained component of the Ca2+ current inactivates slowly, over the course of 15-60 s, in some HCs. This inactivation of the sustained Ca2+ current, when present, is primarily voltage dependent rather than Ca2+ dependent.

Sustained and transient calcium currents in horizontal cells of the white bass retina

PubMed Central

1992-01-01

Calcium currents were recorded from cultured horizontal cells (HCs) isolated from adult white bass retinas, using the whole-cell patch- clamp technique. Ca2+ currents were enhanced using 10 mM extracellular Ca2+, while Na+ and K+ currents were pharmacologically suppressed. Two components of the Ca2+ current, one transient, the other sustained, were found. The large transient component of the Ca2+ current, which has not been seen before in HCs, is similar, but not identical, to the T-type Ca2+ current described previously in a variety of preparations. The sustained component of the Ca2+ current is similar, but not identical, to the L-type current described in other preparations. FTX, a factor isolated from the venom of the funnel-web spider, Agelenopsis aperta, preferentially and irreversibly blocks the sustained component of the Ca2+ current at very dilute concentrations. The sustained component of the Ca2+ current inactivates slowly, over the course of 15- 60 s, in some HCs. This inactivation of the sustained Ca2+ current, when present, is primarily voltage dependent rather than Ca2+ dependent. PMID:1371309

Kinetics of Inhibitory Feedback from Horizontal Cells to Photoreceptors: Implications for an Ephaptic Mechanism

PubMed Central

Warren, Ted J.; Van Hook, Matthew J.; Tranchina, Daniel

2016-01-01

Inhibitory feedback from horizontal cells (HCs) to cones generates center-surround receptive fields and color opponency in the retina. Mechanisms of HC feedback remain unsettled, but one hypothesis proposes that an ephaptic mechanism may alter the extracellular electrical field surrounding photoreceptor synaptic terminals, thereby altering Ca2+ channel activity and photoreceptor output. An ephaptic voltage change produced by current flowing through open channels in the HC membrane should occur with no delay. To test for this mechanism, we measured kinetics of inhibitory feedback currents in Ambystoma tigrinum cones and rods evoked by hyperpolarizing steps applied to synaptically coupled HCs. Hyperpolarizing HCs stimulated inward feedback currents in cones that averaged 8–9 pA and exhibited a biexponential time course with time constants averaging 14–17 ms and 120–220 ms. Measurement of feedback-current kinetics was limited by three factors: (1) HC voltage-clamp speed, (2) cone voltage-clamp speed, and (3) kinetics of Ca2+ channel activation or deactivation in the photoreceptor terminal. These factors totaled ∼4–5 ms in cones meaning that the true fast time constants for HC-to-cone feedback currents were 9–13 ms, slower than expected for ephaptic voltage changes. We also compared speed of feedback to feedforward glutamate release measured at the same cone/HC synapses and found a latency for feedback of 11–14 ms. Inhibitory feedback from HCs to rods was also significantly slower than either measurement kinetics or feedforward release. The finding that inhibitory feedback from HCs to photoreceptors involves a significant delay indicates that it is not due to previously proposed ephaptic mechanisms. SIGNIFICANCE STATEMENT Lateral inhibitory feedback from horizontal cells (HCs) to photoreceptors creates center-surround receptive fields and color-opponent interactions. Although underlying mechanisms remain unsettled, a longstanding hypothesis proposes that feedback is due to ephaptic voltage changes that regulate photoreceptor synaptic output by altering Ca2+ channel activity. Ephaptic processes should occur with no delay. We measured kinetics of inhibitory feedback currents evoked in photoreceptors with voltage steps applied to synaptically coupled HCs and found that feedback is too slow to be explained by ephaptic voltage changes generated by current flowing through continuously open channels in HC membranes. By eliminating the proposed ephaptic mechanism for HC feedback regulation of photoreceptor Ca2+ channels, our data support earlier proposals that synaptic cleft pH changes are more likely responsible. PMID:27683904

Hanford spent nuclear fuel hot conditioning system test procedure

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

Cleveland, K.J.

1997-09-16

This document provides the test procedures for cold testing of the prototype Hot Conditioning System (HCS) at the 306E Facility. The primary objective of this testing is to confirm design choices and provide data for the detailed design package prior to procurement of the process equipment. The current scope of testing in this document includes a fabricability study of the HCS, equipment performance testing of the HCS components, heat-up and cool-down cycle simulation, and robotic arm testing.

Chloride currents in cones modify feedback from horizontal cells to cones in goldfish retina

PubMed Central

Endeman, Duco; Fahrenfort, Iris; Sjoerdsma, Trijntje; Steijaert, Marvin; ten Eikelder, Huub; Kamermans, Maarten

2012-01-01

In neuronal systems, excitation and inhibition must be well balanced to ensure reliable information transfer. The cone/horizontal cell (HC) interaction in the retina is an example of this. Because natural scenes encompass an enormous intensity range both in temporal and spatial domains, the balance between excitation and inhibition in the outer retina needs to be adaptable. How this is achieved is unknown. Using electrophysiological techniques in the isolated retina of the goldfish, it was found that opening Ca2+-dependent Cl− channels in recorded cones reduced the size of feedback responses measured in both cones and HCs. Furthermore, we show that cones express Cl− channels that are gated by GABA released from HCs. Similar to activation of ICl(Ca), opening of these GABA-gated Cl− channels reduced the size of light-induced feedback responses both in cones and HCs. Conversely, application of picrotoxin, a blocker of GABAA and GABAC receptors, had the opposite effect. In addition, reducing GABA release from HCs by blocking GABA transporters also led to an increase in the size of feedback. Because the independent manipulation of Ca2+-dependent Cl− currents in individual cones yielded results comparable to bath-applied GABA, it was concluded that activation of either Cl− current by itself is sufficient to reduce the size of HC feedback. However, additional effects of GABA on outer retinal processing cannot be excluded. These results can be accounted for by an ephaptic feedback model in which a cone Cl− current shunts the current flow in the synaptic cleft. The Ca2+-dependent Cl− current might be essential to set the initial balance between the feedforward and the feedback signals active in the cone HC synapse. It prevents that strong feedback from HCs to cones flood the cone with Ca2+. Modulation of the feedback strength by GABA might play a role during light/dark adaptation, adjusting the amount of negative feedback to the signal to noise ratio of the cone output. PMID:22890705

CellProfiler and KNIME: open source tools for high content screening.

PubMed

Stöter, Martin; Niederlein, Antje; Barsacchi, Rico; Meyenhofer, Felix; Brandl, Holger; Bickle, Marc

2013-01-01

High content screening (HCS) has established itself in the world of the pharmaceutical industry as an essential tool for drug discovery and drug development. HCS is currently starting to enter the academic world and might become a widely used technology. Given the diversity of problems tackled in academic research, HCS could experience some profound changes in the future, mainly with more imaging modalities and smart microscopes being developed. One of the limitations in the establishment of HCS in academia is flexibility and cost. Flexibility is important to be able to adapt the HCS setup to accommodate the multiple different assays typical of academia. Many cost factors cannot be avoided, but the costs of the software packages necessary to analyze large datasets can be reduced by using Open Source software. We present and discuss the Open Source software CellProfiler for image analysis and KNIME for data analysis and data mining that provide software solutions which increase flexibility and keep costs low.

High-content screening for the discovery of pharmacological compounds: advantages, challenges and potential benefits of recent technological developments.

PubMed

Soleilhac, Emmanuelle; Nadon, Robert; Lafanechere, Laurence

2010-02-01

Screening compounds with cell-based assays and microscopy image-based analysis is an approach currently favored for drug discovery. Because of its high information yield, the strategy is called high-content screening (HCS). This review covers the application of HCS in drug discovery and also in basic research of potential new pathways that can be targeted for treatment of pathophysiological diseases. HCS faces several challenges, however, including the extraction of pertinent information from the massive amount of data generated from images. Several proposed approaches to HCS data acquisition and analysis are reviewed. Different solutions from the fields of mathematics, bioinformatics and biotechnology are presented. Potential applications and limits of these recent technical developments are also discussed. HCS is a multidisciplinary and multistep approach for understanding the effects of compounds on biological processes at the cellular level. Reliable results depend on the quality of the overall process and require strong interdisciplinary collaborations.

The asymmetry of the heliospheric current sheet during solar cycle 23: The last dance of the bashful ballerina?

NASA Astrophysics Data System (ADS)

Mursula, K.; Virtanen, I. I.

2010-05-01

The heliospheric magnetic field has long been hemispherically asymmetric so that the field in the northern hemisphere is weaker and the area larger than in the south. This asymmetry, also called the bashful ballerina, has existed during three-year intervals in the late declining to minimum phase of solar cycles 16-22. We study here the HMF and its hemispheric asymmetry during solar cycle 23. We find that the latitudinal ordering of HMF sectors at low latitudes is exceptional in SC 23: the normal latitudinal variation was not established in the south by Spring 2009, implying that the Rosenberg-Coleman rule is abnormally delayed or broken during this cycle. Comparing the radial field at 1AU and at the coronal source surface footpoint, we show that the HCS was southward shifted even in SC 23 but the shift is considerably smaller than in earlier cycles. We also study the HMF observations during the third perihelion pass of the Ulysses probe in 2007, and find that the northern field was some 0.2 nT stronger than the southern field and that the whole HCS region was clearly shifted southward by about 2°-5°. Accordingly, the north-south asymmetry existed even in SC 23 but was largely masked out in ecliptic observations due to the exceptionally weak polar fields, leading to an abnormally large HCS tilt angle and a wide equatorial belt region. We also note that historical evidence at the ecliptic suggests a connection between solar dipole strength and the size of north-south asymmetry observed there. Based on this, one can predict that, after the present period of weak solar activity started in SC 23, the hemispheric asymmetry will grow again with increasing activity, but the orientation of the asymmetry will be opposite. Thus, after SC 23, the solar ballerina will not be bashful for some 100-150 years.

The POIS (Parkland On-Line Information System) Implementation of the IBM Health Care Support/Patient Care System

PubMed Central

Mishelevich, David J.; Hudson, Betty G.; Van Slyke, Donald; Mize, Elaine I.; Robinson, Anna L.; Brieden, Helen C.; Atkinson, Jack; Robertson, James

1980-01-01

The installation of major components of a comprehensive Hospital Information System (HIS) called POIS, the Parkland On-line Information System, including identified success factors is described for the Dallas County Hospital District (DCHD) known also as the Parkland Memorial Hospital. Installation of the on-line IBM Health Care Support (HCS) Registration and Admissions Packages occurred in 1976 and implementation of the HCS Patient Care System (PCS) began in 1977 which includes on-line support of health care areas such as nursing stations and ancillary areas. The Duke Hospital Information System (DHIS) is marketed as the IBM HCS/Patient Care System (PCS). DCHD was the validation site. POIS has order entry, result reporting and work management components. While most of the patient care components are currently installed for the inpatient service, the Laboratories are being installed for the outpatient and Emergency areas as well. The Clinic Appointment System developed at the University of Michigan is also installed. The HCS family of programs use DL/1 and CICS and were installed in the OS versions, currently running under MVS on an IBM 370/168 Model 3 with 8 megabytes of main memory. ImagesFigure 1-AFigure 1-B

Hemichannels in neurodegenerative diseases: is there a link to pathology?

PubMed Central

Bosch, Megan; Kielian, Tammy

2014-01-01

Although originally considered a structural component of gap junctions, connexin hemichannels (HCs) are now recognized as functional entities capable of influencing metabolic gradients within the CNS, allowing direct communication between the intra- and extracellular milieus. Besides connexins, HCs can also be formed by pannexins, which are not capable of gap junction assembly. Both positive and negative effects have been attributed to HC activity in the context of neurodegenerative diseases. For example, HCs can exert neuroprotective effects by promoting the uptake of neurotoxic molecules, whereas chronic HC opening can disrupt molecular gradients leading to cellular dysfunction and death. The latter scenario has been suggested for multiple neurodegenerative disorders, including Alzheimer’s disease (AD) and more recently, lysosomal storage disorders, which are the focus of this perspective. Currently available evidence suggests a complex role for HCs in neurodegenerative disorders, which sets the stage for future studies to determine whether targeting HC action may improve disease outcomes. PMID:25191227

Drift effects on the galactic cosmic ray modulation

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

Laurenza, M.; Storini, M.; Vecchio, A.

2014-02-01

Cosmic ray (CR) modulation is driven by both solar activity and drift effects in the heliosphere, although their role is only qualitatively understood as it is difficult to connect the CR variations to their sources. In order to address this problem, the Empirical Mode Decomposition technique has been applied to the CR intensity, recorded by three neutron monitors at different rigidities (Climax, Rome, and Huancayo-Haleakala (HH)), the sunspot area, as a proxy for solar activity, the heliospheric magnetic field magnitude, directly related to CR propagation, and the tilt angle (TA) of the heliospheric current sheet (HCS), which characterizes drift effectsmore » on CRs. A prominent periodicity at ∼six years is detected in all the analyzed CR data sets and it is found to be highly correlated with changes in the HCS inclination at the same timescale. In addition, this variation is found to be responsible for the main features of the CR modulation during periods of low solar activity, such as the flat (peaked) maximum in even (odd) solar cycles. The contribution of the drift effects to the global Galactic CR modulation has been estimated to be between 30% and 35%, depending on the CR particle energy. Nevertheless, the importance of the drift contribution is generally reduced in periods nearing the sunspot maximum. Finally, threshold values of ∼40°, ∼45°, and >55° have been derived for the TA, critical for the CR modulation at the Climax, Rome, and HH rigidity thresholds, respectively.« less

Short Term Exogenic Climate Change Forcing

NASA Astrophysics Data System (ADS)

Krahenbuhl, Daniel

Several short term exogenic forcings affecting Earth's climate are but recently identified. Lunar nutation periodicity has implications for numerical meteorological prediction. Abrupt shifts in solar wind bulk velocity, particle density, and polarity exhibit correlation with terrestrial hemispheric vorticity changes, cyclonic strengthening and the intensification of baroclinic disturbances. Galactic Cosmic ray induced tropospheric ionization modifies cloud microphysics, and modulates the global electric circuit. This dissertation is constructed around three research questions: (1): What are the biweekly declination effects of lunar gravitation upon the troposphere? (2): How do United States severe weather reports correlate with heliospheric current sheet crossings? and (3): How does cloud cover spatially and temporally vary with galactic cosmic rays? Study 1 findings show spatial consistency concerning lunar declination extremes upon Rossby longwaves. Due to the influence of Rossby longwaves on synoptic scale circulation, our results could theoretically extend numerical meteorological forecasting. Study 2 results indicate a preference for violent tornadoes to occur prior to a HCS crossing. Violent tornadoes (EF3+) are 10% more probable to occur near, and 4% less probable immediately after a HCS crossing. The distribution of hail and damaging wind reports do not mirror this pattern. Polarity is critical for the effect. Study 3 results confirm anticorrelation between solar flux and low-level marine-layer cloud cover, but indicate substantial regional variability between cloud cover altitude and GCRs. Ultimately, this dissertation serves to extend short term meteorological forecasting, enhance climatological modeling and through analysis of severe violent weather and heliospheric events, protect property and save lives.

Heliospheric plasma sheet (HPS) impingement onto the magnetosphere as a cause of relativistic electron dropouts (REDs) via coherent EMIC wave scattering with possible consequences for climate change mechanisms

NASA Astrophysics Data System (ADS)

Tsurutani, B. T.; Hajra, R.; Tanimori, T.; Takada, A.; Bhanu, R.; Mannucci, A. J.; Lakhina, G. S.; Kozyra, J. U.; Shiokawa, K.; Lee, L. C.; Echer, E.; Reddy, R. V.; Gonzalez, W. D.

2016-10-01

A new scenario is presented for the cause of magnetospheric relativistic electron decreases (REDs) and potential effects in the atmosphere and on climate. High-density solar wind heliospheric plasmasheet (HPS) events impinge onto the magnetosphere, compressing it along with remnant noon-sector outer-zone magnetospheric 10-100 keV protons. The betatron accelerated protons generate coherent electromagnetic ion cyclotron (EMIC) waves through a temperature anisotropy (T⊥/T|| > 1) instability. The waves in turn interact with relativistic electrons and cause the rapid loss of these particles to a small region of the atmosphere. A peak total energy deposition of 3 × 1020 ergs is derived for the precipitating electrons. Maximum energy deposition and creation of electron-ion pairs at 30-50 km and at < 30 km altitude are quantified. We focus the readers' attention on the relevance of this present work to two climate change mechanisms. Wilcox et al. (1973) noted a correlation between solar wind heliospheric current sheet (HCS) crossings and high atmospheric vorticity centers at 300 mb altitude. Tinsley et al. has constructed a global circuit model which depends on particle precipitation into the atmosphere. Other possible scenarios potentially affecting weather/climate change are also discussed.

Extracellular gentamicin reduces the activity of connexin hemichannels and interferes with purinergic Ca2+ signaling in HeLa cells

PubMed Central

Figueroa, Vania A.; Retamal, Mauricio A.; Cea, Luis A.; Salas, José D.; Vargas, Aníbal A.; Verdugo, Christian A.; Jara, Oscar; Martínez, Agustín D.; Sáez, Juan C.

2014-01-01

Gap junction channels (GJCs) and hemichannels (HCs) are composed of protein subunits termed connexins (Cxs) and are permeable to ions and small molecules. In most organs, GJCs communicate the cytoplasm of adjacent cells, while HCs communicate the intra and extracellular compartments. In this way, both channel types coordinate physiological responses of cell communities. Cx mutations explain several genetic diseases, including about 50% of autosomal recessive non-syndromic hearing loss. However, the possible involvement of Cxs in the etiology of acquired hearing loss remains virtually unknown. Factors that induce post-lingual hearing loss are diverse, exposure to gentamicin an aminoglycoside antibiotic, being the most common. Gentamicin has been proposed to block GJCs, but its effect on HCs remains unknown. In this work, the effect of gentamicin on the functional state of HCs was studied and its effect on GJCs was reevaluated in HeLa cells stably transfected with Cxs. We focused on Cx26 because it is the main Cx expressed in the cochlea of mammals where it participates in purinergic signaling pathways. We found that gentamicin applied extracellularly reduces the activity of HCs, while dye transfer across GJCs was not affected. HCs were also blocked by streptomycin, another aminoglycoside antibiotic. Gentamicin also reduced the adenosine triphosphate release and the HC-dependent oscillations of cytosolic free-Ca2+ signal. Moreover, gentamicin drastically reduced the Cx26 HC-mediated membrane currents in Xenopus laevis oocytes. Therefore, the extracellular gentamicin-induced inhibition of Cx HCs may adversely affect autocrine and paracrine signaling, including the purinergic one, which might partially explain its ototoxic effects. PMID:25237294

Versatile functional roles of horizontal cells in the retinal circuit.

PubMed

Chaya, Taro; Matsumoto, Akihiro; Sugita, Yuko; Watanabe, Satoshi; Kuwahara, Ryusuke; Tachibana, Masao; Furukawa, Takahisa

2017-07-17

In the retinal circuit, environmental light signals are converted into electrical signals that can be decoded properly by the brain. At the first synapse of the visual system, information flow from photoreceptors to bipolar cells is modulated by horizontal cells (HCs), however, their functional contribution to retinal output and individual visual function is not fully understood. In the current study, we investigated functional roles for HCs in retinal ganglion cell (RGC) response properties and optokinetic responses by establishing a HC-depleted mouse line. We observed that HC depletion impairs the antagonistic center-surround receptive field formation of RGCs, supporting a previously reported HC function revealed by pharmacological approaches. In addition, we found that HC loss reduces both the ON and OFF response diversities of RGCs, impairs adjustment of the sensitivity to ambient light at the retinal output level, and alters spatial frequency tuning at an individual level. Taken together, our current study suggests multiple functional aspects of HCs crucial for visual processing.

Tracking CMEs using data from the Solar Stormwatch project; observing deflections and other properties

NASA Astrophysics Data System (ADS)

Jones, Shannon R.; Barnard, Luke A.; Scott, Christopher J.; Owens, Mathew J.; Wilkinson, Julia

2017-09-01

With increasing technological dependence, society is becoming ever more affected by changes in the near-Earth space environment caused by space weather. The primary driver of these hazards are coronal mass ejections (CMEs). Solar Stormwatch is a citizen science project in which volunteers participated in several activities which characterized CMEs in the remote sensing images from the Sun Earth Connection Coronal and Heliospheric Investigation (SECCHI) instrument package on the twin STEREO spacecraft. Here we analyze the results of the "Track-it-back" activity, in which CMEs were tracked back through the COR1, COR2, and EUVI images. Analysis of the COR1, COR2, and EUVI data together allows CMEs to be studied consistently throughout the whole field of view spanned by these instruments (out to 15 RS). A total of 4783 volunteers took part in this activity, creating a data set containing 23,801 estimates of CME timing, location, and size. We used these data to produce a catalogue of 41 CMEs, which is the first to consistently track CMEs through each of these instruments. We assess how the CME speeds, propagation directions, and widths vary as the CMEs propagate through the fields of view of the different imagers. In particular, we compare the observed CME deflections between the COR1 and COR2 fields of view to the separation between the CME source region and the heliospheric current sheet (HCS), demonstrating that in general, these CMEs appear to deflect toward the HCS, consistent with other modeling studies of CME propagation.

Process Optimization of Dual-Laser Beam Welding of Advanced Al-Li Alloys Through Hot Cracking Susceptibility Modeling

NASA Astrophysics Data System (ADS)

Tian, Yingtao; Robson, Joseph D.; Riekehr, Stefan; Kashaev, Nikolai; Wang, Li; Lowe, Tristan; Karanika, Alexandra

2016-07-01

Laser welding of advanced Al-Li alloys has been developed to meet the increasing demand for light-weight and high-strength aerospace structures. However, welding of high-strength Al-Li alloys can be problematic due to the tendency for hot cracking. Finding suitable welding parameters and filler material for this combination currently requires extensive and costly trial and error experimentation. The present work describes a novel coupled model to predict hot crack susceptibility (HCS) in Al-Li welds. Such a model can be used to shortcut the weld development process. The coupled model combines finite element process simulation with a two-level HCS model. The finite element process model predicts thermal field data for the subsequent HCS hot cracking prediction. The model can be used to predict the influences of filler wire composition and welding parameters on HCS. The modeling results have been validated by comparing predictions with results from fully instrumented laser welds performed under a range of process parameters and analyzed using high-resolution X-ray tomography to identify weld defects. It is shown that the model is capable of accurately predicting the thermal field around the weld and the trend of HCS as a function of process parameters.

Experimental Recreation of Large-Scale Coastal Bedforms and Hummocky Cross-Stratification in Sheet Flow Conditions

NASA Astrophysics Data System (ADS)

Vermaas, T.; Kleinhans, M. G.; Huisman, C.; Schretlen, J. L.; van der Werf, J. J.; Ribberink, J. S.; Ruessink, G.

2010-12-01

In shallow marine environments various types of large bed forms emerge under waves and currents. There is no consensus on whether and how these bedforms can be classified in a genetically meaningful sense. Hypotheses for their genesis vary from a large variety of causal mechanisms for a number of different ripples to a single growing instability mechanism, reflecting a limited understanding. Our objective is to understand the formative mechanism of a family of large bedforms referred to as Large Wave Ripples in coastal literature and Hummocks in sedimentological literature, which also describes the hummocky cross stratification (HCS) found in the sedimentary rock record. The formative conditions for hummocks have been debated extensively, particularly whether currents or specific particle sizes were required. We collected and compared existing field and laboratory data and we conducted a full scale experiment in the Hannover Grosse Welle wave flume (300 m long, 5 m wide and 7 m deep). Experiments were done for several conditions, including a storm sequence, with 0.7-1.7 m regular trochoidal waves or irregular waves with periods of 5-7.5 s over sand with mean particle sizes of 0.256 (in 2007) or 0.137 mm (in 2008). Bed profiles were collected mechanically and acoustically. A conductivity probe (CCM) was used to measure sheet flow thickness or absence and near-bed flow and suspended sand concentrations were measured in detail with acoustical profilers. From the data collection, we found that there is no distinction empirically between LWR and Hummocks. Both are found around the inception of sheet flow and have the same dimensions. In the experiments we produced short wave ripples superimposed on large wave ripples below and in the transition to sheet flow conditions. The SWR were well predicted by a recent particle-size dependent ripple length predictor. No available predictor matched the LWR dimensions. The LWR remained present in strong sheet flow conditions and migrated slowly in the direction of wave advance due to wave asymmetry. LWR height was less than 0.07 m whilst lengths were about 13 m. Despite the sheet flow conditions and fine sediment, the LWR scaled as orbital ripples though a factor of 2 longer (i.e. with the orbital diameter d = uT/pi with u the orbital velocity amplitude and T the wave period). Laquer peels of the 2007 experiment demonstrated that the LWR formed Hummocky Cross-Stratification. We conclude that hummocks were experimentally created in a full-scale facility during sheet flow conditions without currents. Furthermore, LWR and hummocks are the same features.

Multifarious anchovy and sardine regimes in the Humboldt Current System during the last 150 years.

PubMed

Salvatteci, Renato; Field, David; Gutiérrez, Dimitri; Baumgartner, Tim; Ferreira, Vicente; Ortlieb, Luc; Sifeddine, Abdel; Grados, Daniel; Bertrand, Arnaud

2018-03-01

The Humboldt Current System (HCS) has the highest production of forage fish in the world, although it is highly variable and the future of the primary component, anchovy, is uncertain in the context of global warming. Paradigms based on late 20th century observations suggest that large-scale forcing controls decadal-scale fluctuations of anchovy and sardine across different boundary currents of the Pacific. We develop records of anchovy and sardine fluctuations since 1860 AD using fish scales from multiple sites containing laminated sediments and compare them with Pacific basin-scale and regional indices of ocean climate variability. Our records reveal two main anchovy and sardine phases with a timescale that is not consistent with previously proposed periodicities. Rather, the regime shifts in the HCS are related to 3D habitat changes driven by changes in upwelling intensity from both regional and large-scale forcing. Moreover, we show that a long-term increase in coastal upwelling translates via a bottom-up mechanism to top predators suggesting that the warming climate, at least up to the start of the 21st century, was favorable for fishery productivity in the HCS. © 2017 John Wiley & Sons Ltd.

The association between discontinuing hormonal contraceptives and wives’ marital satisfaction depends on husbands’ facial attractiveness

PubMed Central

Russell, V. Michelle; McNulty, James K.; Baker, Levi R.; Meltzer, Andrea L.

2014-01-01

How are hormonal contraceptives (HCs) related to marital well-being? Some work suggests HCs suppress biological processes associated with women’s preferences for partner qualities reflective of genetic fitness, qualities that may be summarized by facial attractiveness. Given that realizing such interpersonal preferences positively predicts relationship satisfaction, any changes in women’s preferences associated with changes in their HC use may interact with partner facial attractiveness to predict women’s relationship satisfaction. We tested this possibility using two longitudinal studies of 118 newlywed couples. Trained observers objectively rated husbands’ facial attractiveness in both studies. In study 1, wives reported their marital satisfaction every 6 mo for 4 y and then reported the history of their HC use for their relationship. In study 2, wives reported whether they were using HCs when they met their husbands and then their marital satisfaction and HC use every 4 mo for up to three waves. In both studies, and in an analysis that combined the data from both studies, wives who were using HCs when they formed their relationship with their husband were less satisfied with their marriage when they discontinued HCs if their husband had a relatively less attractive face, but more satisfied if their husband had a relatively more attractive face. Beginning HCs demonstrated no consistent associations with marital satisfaction. Incongruency between HC use at relationship formation and current HC use was negatively associated with sexual satisfaction, regardless of husbands’ facial attractiveness. These findings suggest that HC use may have unintended implications for women’s close relationships. PMID:25404285

The association between discontinuing hormonal contraceptives and wives' marital satisfaction depends on husbands' facial attractiveness.

PubMed

Russell, V Michelle; McNulty, James K; Baker, Levi R; Meltzer, Andrea L

2014-12-02

How are hormonal contraceptives (HCs) related to marital well-being? Some work suggests HCs suppress biological processes associated with women's preferences for partner qualities reflective of genetic fitness, qualities that may be summarized by facial attractiveness. Given that realizing such interpersonal preferences positively predicts relationship satisfaction, any changes in women's preferences associated with changes in their HC use may interact with partner facial attractiveness to predict women's relationship satisfaction. We tested this possibility using two longitudinal studies of 118 newlywed couples. Trained observers objectively rated husbands' facial attractiveness in both studies. In study 1, wives reported their marital satisfaction every 6 mo for 4 y and then reported the history of their HC use for their relationship. In study 2, wives reported whether they were using HCs when they met their husbands and then their marital satisfaction and HC use every 4 mo for up to three waves. In both studies, and in an analysis that combined the data from both studies, wives who were using HCs when they formed their relationship with their husband were less satisfied with their marriage when they discontinued HCs if their husband had a relatively less attractive face, but more satisfied if their husband had a relatively more attractive face. Beginning HCs demonstrated no consistent associations with marital satisfaction. Incongruency between HC use at relationship formation and current HC use was negatively associated with sexual satisfaction, regardless of husbands' facial attractiveness. These findings suggest that HC use may have unintended implications for women's close relationships.

Electronic laboratory system reduces errors in National Tuberculosis Program: a cluster randomized controlled trial.

PubMed

Blaya, J A; Shin, S S; Yale, G; Suarez, C; Asencios, L; Contreras, C; Rodriguez, P; Kim, J; Cegielski, P; Fraser, H S F

2010-08-01

To evaluate the impact of the e-Chasqui laboratory information system in reducing reporting errors compared to the current paper system. Cluster randomized controlled trial in 76 health centers (HCs) between 2004 and 2008. Baseline data were collected every 4 months for 12 months. HCs were then randomly assigned to intervention (e-Chasqui) or control (paper). Further data were collected for the same months the following year. Comparisons were made between intervention and control HCs, and before and after the intervention. Intervention HCs had respectively 82% and 87% fewer errors in reporting results for drug susceptibility tests (2.1% vs. 11.9%, P = 0.001, OR 0.17, 95%CI 0.09-0.31) and cultures (2.0% vs. 15.1%, P < 0.001, OR 0.13, 95%CI 0.07-0.24), than control HCs. Preventing missing results through online viewing accounted for at least 72% of all errors. e-Chasqui users sent on average three electronic error reports per week to the laboratories. e-Chasqui reduced the number of missing laboratory results at point-of-care health centers. Clinical users confirmed viewing electronic results not available on paper. Reporting errors to the laboratory using e-Chasqui promoted continuous quality improvement. The e-Chasqui laboratory information system is an important part of laboratory infrastructure improvements to support multidrug-resistant tuberculosis care in Peru.

Trends in physician house calls to Medicare beneficiaries.

PubMed

Peterson, Lars E; Landers, Steven H; Bazemore, Andrew

2012-01-01

House calls (HCs) to older adults seemed to be headed for extinction in recent decades. HCs may be a tool to ensure access and reduce institutionalization of the elderly population. This study determines the number and distribution of HCs by physician specialty over time and analyzes associations of providing HCs with physician and area-level characteristics. This study was a cross-sectional analysis of 3 complete Medicare Part B claims data for national state-representative samples of physicians in 2000, 2003, and 2006. Multilevel logistic regression determined associations between physician and area-level characteristics and provision of HCs in 2006. Physicians made 478,088 HCs in 2000; 700,661 in 2003; and 995,294 in 2006. Over the same period, the proportion of physicians making HCs decreased from 7.22 (standard error, ±0.20) to 5.26 (±0.19). Physicians in the top decile of HC volume made an increasing number of HCs (median, 56 in 2000 and 86 in 2006). In 2006, physicians who made HCs were more likely to be older, geriatricians, and osteopaths, be in solo practice, and reside in rural areas compared with those who did not make HCs. Between 2000 and 2006, the number of physician HCs to Medicare beneficiaries more than doubled, whereas the number of physicians making HCs declined.

North-south asymmetry in the magnetic deflection of polar coronal hole jets

NASA Astrophysics Data System (ADS)

Nisticò, G.; Zimbardo, G.; Patsourakos, S.; Bothmer, V.; Nakariakov, V. M.

2015-11-01

Context. Measurements of the sunspots area, of the magnetic field in the interplanetary medium, and of the heliospheric current sheet (HCS) position, reveal a possible north-south (N-S) asymmetry in the magnetic field of the Sun. This asymmetry could cause the bending of the HCS of the order of 5-10 deg in the southward direction, and it appears to be a recurrent characteristic of the Sun during the minima of solar activity. Aims: We study the N-S asymmetry as inferred from measurements of the deflection of polar coronal hole jets when they propagate throughout the corona. Methods: Since the corona is an environment where the magnetic pressure is greater than the kinetic pressure (β ≪ 1), we can assume that the magnetic field controls the dynamics of plasma. On average, jets follow magnetic field lines during their propagation, highlighting their local direction. We measured the position angles at 1 R⊙ and at 2 R⊙ of 79 jets, based on the Solar TErrestrial RElations Observatory (STEREO) ultraviolet and white-light coronagraph observations during the solar minimum period March 2007-April 2008. The average jet deflection is studied both in the plane perpendicular to the line of sight and, for a reduced number of jets, in 3D space. The observed jet deflection is studied in terms of an axisymmetric magnetic field model comprising dipole (g1), quadrupole (g2), and esapole (g3) moments. Results: We found that the propagation of the jets is not radial, which is in agreement with the deflection due to magnetic field lines. Moreover, the amount of the deflection is different between jets over the north and those from the south pole. A comparison of jet deflections and field line tracing shows that a ratio g2/g1 ≃ -0.5 for the quadrupole and a ratio g3/g1 ≃ 1.6-2.0 for the esapole can describe the field. The presence of a non-negligible quadrupole moment confirms the N-S asymmetry of the solar magnetic field for the considered period. Conclusions: We find that the magnetic deflection of jets is larger in the north than in the south of the order of 25-40%, with an asymmetry that is consistent with a southward deflection of the heliospheric current sheet of the order of 10 deg, consistent with that inferred from other independent datasets and instruments.

Measuring the efficiency of the Greek rural primary health care using a restricted DEA model; the case of southern and western Greece.

PubMed

Oikonomou, Nikolaos; Tountas, Yannis; Mariolis, Argiris; Souliotis, Kyriakos; Athanasakis, Kostas; Kyriopoulos, John

2016-12-01

This is a study to measure the efficiency of the rural Health Centres (HCs) and their Regional Surgeries (RSs) of the 6th Health Prefecture (HP) of Greece, which covers Southern and Western Greece. Data Envelopment Analysis (DEA) was applied under Constant and Variable Returns to Scale, using a weight-restricted, output-oriented model, to calculate pure technical efficiency (PΤΕ), scale efficiency (SE) and total technical efficiency (TE). The selection of inputs, outputs and their relative weights in the model was based on two consecutive consensus panels of experts on Primary Health Care (PHC). Medical personnel, nursing personnel and technological equipment were chosen as inputs and were attributed appropriate weight restrictions. Acute, chronic and preventive consultations where chosen as outputs; each output was constructed by smaller subcategories of different relative importance. Data were collected through a questionnaire sent to all HCs of the covered area. From the 42 HCs which provided complete data, the study identified 9 as technical efficient, 5 as scale efficient and 2 as total efficient. The mean TE, PTE and SE scores of the HCs of the 6th Health Prefecture were 0.57, 0.67 and 0.87, respectively. The results demonstrate noteworthy variation in efficiency in the productive process of the HCs of Southern and Western Greece. The dominant form of inefficiency was technical inefficiency. The HCs of the 6th HP can theoretically produce 33 % more output on average, using their current production factors. These results indicated potential for considerable efficiency improvement in most rural health care units. Emphasis on prevention and chronic disease management, as well as wider structural and organisational reforms, are discussed from the viewpoint of how to increase efficiency.

HELIOSHEATH MAGNETIC FIELDS BETWEEN 104 AND 113 AU IN A REGION OF DECLINING SPEEDS AND A STAGNATION REGION

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

Burlaga, L. F.; Ness, N. F., E-mail: lburlagahsp@verizon.net, E-mail: nfnudel@yahoo.com

2012-04-10

We examine the relationships between the magnetic field and the radial velocity component V{sub R} observed in the heliosheath by instruments on Voyager 1 (V1). No increase in the magnetic field strength B was observed in a region where V{sub R} decreased linearly from 70 km s{sup -1} to 0 km s{sup -1} as plasma moved outward past V1. An unusually broad transition from positive to negative polarity was observed during a Almost-Equal-To 26 day interval when the heliospheric current sheet (HCS) moved below the latitude of V1 and the speed of V1 was comparable to the radial speed ofmore » the heliosheath flow. When V1 moved through a region where V{sub R} Almost-Equal-To 0 (the 'stagnation region'), B increased linearly with time by a factor of two, and the average of B was 0.14 nT. Nothing comparable to this was observed previously. The magnetic polarity was negative throughout the stagnation region for Almost-Equal-To 580 days until 2011 DOY 235, indicating that the HCS was below the latitude of V1. The average passage times of the magnetic holes and proton boundary layers were the same during 2009 and 2011, because the plasma moved past V1 during 2009 at the same speed that V1 moved through the stagnation region during 2011. The microscale fluctuations of B in the stagnation region during 2011 are qualitatively the same as those observed in the heliosheath during 2009. These results suggest that the stagnation region is a part of the heliosheath, rather than a 'transition region' associated with the heliopause.« less

The wide skirt of the bashful ballerina: Hemispheric asymmetry of the heliospheric magnetic field in the inner and outer heliosphere

NASA Astrophysics Data System (ADS)

Mursula, K.; Virtanen, I.

2012-04-01

We reanalyze the observations of the heliospheric magnetic field (HMF) made by the Pioneer 10 and 11 and Voyager 1 and 2 heliospheric probes since 1972, and calculate the HMF sector occurrence ratios and tangential component strengths in the different regions of the heliosphere. Observations at the distant probes and at 1 AU show a very consistent picture of the HMF sector structure in the entire heliosphere, and even beyond the termination shock. Pioneer 11 and Voyager 1 show that the development of northern polar coronal holes was very systematic and active during all the four solar minima since mid-1970s. On the other hand, Voyager 2 observations show a less systematic and delayed development of southern coronal holes in 1980s, 1990s and 2000s. This delay in the evolution of southern coronal holes with respect to the rapid and systematic evolution of northern coronal holes leads to a larger extent of northern coronal holes and a southward shift of the heliospheric current sheet (the bashful ballerina phenomenon) for a few years in the late declining phase of each solar cycle. HMF observations of the probes also directly verify the HCS southward shift, supporting earlier observations at 1-2 AU by the Ulysses probe and Earth-orbiting satellites and extending them into the more distant heliosphere. Although the evidence for the connection between the temporal difference in the evolution of polar coronal holes and the bashful ballerina times is based only on three solar cycles, this may be a common pattern for solar coronal hole evolution since the southward shift of the HCS has occurred at least since solar cycle 16.

Systematically Asymmetric Heliospheric Magnetic Field: Evidence for a Quadrupole Mode and Non-Axisymmetry with Polarity Flip-Flops

NASA Astrophysics Data System (ADS)

Mursula, K.; Hiltula, T.

2004-10-01

Recent studies of the heliospheric magnetic field (HMF) have detected interesting, systematic hemispherical and longitudinal asymmetries which have a profound significance for the understanding of solar magnetic fields. The in situ HMF measurements since the 1960s show that the heliospheric current sheet (HCS) is systematically shifted (coned) southward during solar minimum times, leading to the concept of a bashful ballerina. While temporary shifts can be considerably larger, the average HCS shift (coning) angle is a few degrees, less than the 7.2∘ tilt of the solar rotation axis. Recent solar observations during the last two solar cycles verify these results and show that the magnetic areas in the northern solar hemisphere are larger and their intensity weaker than in the south during long intervals in the late declining to minimum phase. The multipole expansion reveals a strong quadrupole term which is oppositely directed to the dipole term. These results imply that the Sun has a symmetric quadrupole S0 dynamo mode that oscillates in phase with the dominant dipole A0 mode. Moreover, the heliospheric magnetic field has a strong tendency to produce solar tilts that are roughly opposite in longitudinal phase. This implies is a systematic longitudinal asymmetry and leads to a “flip-flop” type behaviour in the dominant HMF sector whose period is about 3.2 years. This agrees very well with the similar flip-flop period found recently in sunspots, as well as with the observed ratio of three between the activity cycle period and the flip-flop period of sun-like stars. Accordingly, these results require that the solar dynamo includes three modes, A0, S0 and a non-axisymmetric mode. Obviously, these results have a great impact on solar modelling.

Bashful ballerina: The asymmetric Sun viewed from the heliosphere

NASA Astrophysics Data System (ADS)

Mursula, K.

Long-term observations of the heliospheric magnetic field (HMF) at 1 AU have depicted interesting systematic hemispheric and longitudinal asymmetries that have far-reaching implications for the understanding of solar magnetism. It has recently been found that the HMF sector that is prevalent in the northern solar hemisphere dominates the observed HMF sector occurrence for a few years in the late declining to minimum phase of the solar cycle. This leads to a persistent southward shift or coning of the heliospheric current sheet (HCS) at these times, which has been described by the concept of the bashful ballerina. This result was later verified by direct measurements of the solar magnetic field which showed that the average field intensity was smaller and the corresponding area larger in the northern (heliographic) hemisphere than in the southern hemisphere during roughly 3 years in the late declining to minimum phase of the cycle. During these years when the HCS was shifted southwards, the solar quadrupole moment was found to be systematically non-zero and oppositely oriented with respect to the dipole moment. Long-term observations of the geomagnetic field can yield information on the HMF sector structure in the pre-satellite era, showing that the ballerina was bashful since 1930s. In addition to the hemispheric asymmetries, the Sun is systematically asymmetric in longitude. It has been shown that the global HMF has persistent active longitudes whose dominance depicts an oscillation with a period of about 3.2 years. Accordingly, the bashful ballerina takes three such steps per activity cycle, thus dancing in waltz tempo. Stellar observations show that this is a general pattern for sun-like cool stars. We describe these phenomena and discuss their implications.

Childhood Trauma and Current Psychological Functioning in Adults with Social Anxiety Disorder

PubMed Central

Kuo, Janice R.; Goldin, Philippe R.; Werner, Kelly; Heimberg, Richard G.; Gross, James J.

2011-01-01

Etiological models of social anxiety disorder (SAD) suggest that early childhood trauma contributes to the development of this disorder. However, surprisingly little is known about the link between different forms of childhood trauma and adult clinical symptoms in SAD. This study (1) compared levels of childhood trauma in adults with generalized SAD versus healthy controls (HCs), and (2) examined the relationship between specific types of childhood trauma and adult clinical symptoms in SAD. Participants were 102 individuals with generalized SAD and 30 HCs who completed measures of childhood trauma, social anxiety, trait anxiety, depression, and self-esteem. Compared to HCs, individuals with SAD reported greater childhood emotional abuse and emotional neglect. Within the SAD group, childhood emotional abuse and neglect, but not sexual abuse, physical abuse, or physical neglect, were associated with the severity of social anxiety, trait anxiety, depression, and self-esteem. PMID:21183310

Childhood trauma and current psychological functioning in adults with social anxiety disorder.

PubMed

Kuo, Janice R; Goldin, Philippe R; Werner, Kelly; Heimberg, Richard G; Gross, James J

2011-05-01

Etiological models of social anxiety disorder (SAD) suggest that early childhood trauma contributes to the development of this disorder. However, surprisingly little is known about the link between different forms of childhood trauma and adult clinical symptoms in SAD. This study (1) compared levels of childhood trauma in adults with generalized SAD versus healthy controls (HCs), and (2) examined the relationship between specific types of childhood trauma and adult clinical symptoms in SAD. Participants were 102 individuals with generalized SAD and 30 HCs who completed measures of childhood trauma, social anxiety, trait anxiety, depression, and self-esteem. Compared to HCs, individuals with SAD reported greater childhood emotional abuse and emotional neglect. Within the SAD group, childhood emotional abuse and neglect, but not sexual abuse, physical abuse, or physical neglect, were associated with the severity of social anxiety, trait anxiety, depression, and self-esteem. Copyright © 2010 Elsevier Ltd. All rights reserved.

The Humboldt Current System: Ecosystem components and processes, fisheries, and sediment studies

NASA Astrophysics Data System (ADS)

Montecino, Vivian; Lange, Carina B.

2009-12-01

In the Humboldt Current System (HCS), biological and non-biological components, ecosystem processes, and fisheries are known to be affected by multi-decadal, inter-annual, annual, and intra-seasonal scales. The interplay between atmospheric variability, the poleward undercurrent, the shallow oxygen minimum zone (OMZ), and the fertilizing effect of coastal upwelling and overall high primary production rates drive bio-physical interactions, the carbon biomass, and fluxes of gases and particulate and dissolved matter through the water column. Coastal upwelling (permanent and seasonally modulated off Peru and northern Chile, and markedly seasonal between 30°S and 40°S) is the key process responsible for the high biological productivity in the HCS. At present, the western coast of South America produces more fish per unit area than any other region in the world ocean (i.e. ∼7.5 × 10 6 t of anchoveta were landed in 2007). Climate changes on different temporal scales lead to alterations in the distribution ranges of anchoveta and sardine populations and shifts in their dominance throughout the HCS. The factors affecting the coastal marine ecosystem that reverberate in the fisheries are crucial from a social perspective, since the economic consequences of mismanagement can be severe. Fish remains are often well-preserved in sediment settings under the hypoxic conditions of the OMZ off Peru and Chile, and reveal multi-decadal variability and centennial-scale changes in fish populations. Sediment studies from the Chilean continental margin encompassing the last 20,000 years of deposition reveal changes in sub-surface conditions in the HCS during deglaciation, interpreted to include: a major reorganization of the OMZ; a deglacial increase in denitrification decoupled from local marine productivity; and higher deglacial and Holocene paleoproductivities compared to the Last Glacial Maximum in central-south Chile (35-37°S) while this scheme is reversed for north-central Chile. Multi-scale, interdisciplinary approaches and focused research groups are needed to understand air-sea interactions, plankton dynamics, biomass removal by fisheries, and the transformation and fluxes of matter across the different HCS components. In this paper, we present a multidisciplinary synthesis of the HCS that covers its physics, atmosphere, primary and secondary production, medium and high trophic levels, fisheries including management aspects, and relevant sedimentary studies.

Comparative analysis of novel autoantibody isotypes against citrullinated-inter-alpha-trypsin inhibitor heavy chain 3 (ITIH3)(542-556) peptide in serum from Taiwanese females with rheumatoid arthritis, primary Sjögren's syndrome and secondary Sjögren's syndrome in rheumatoid arthritis.

PubMed

Liao, Chen-Chung; Chou, Pei-Lun; Cheng, Chao-Wen; Chang, Yu-Sheng; Chi, Wei-Ming; Tsai, Kai-Leun; Chen, Wei-Jung; Kung, Ting-Shuan; Tai, Chih-Chun; Lee, Kuan-Wei; Chen, You-Chia; Lin, Ching-Yu

2016-06-01

The purpose of this study was to discover and validate inter-alpha-trypsin inhibitor heavy chain H3 (ITIH3) as novel biomarkers, and evaluate autoantibody isotypes against an unmodified and citrullinated ITIH3(542-556) peptide among Taiwanese female patients with rheumatoid arthritis (RA), primary Sjögren's syndrome (pSS), secondary Sjögren's syndrome in rheumatoid arthritis (RA-sSS), and healthy controls (HCs). We used concanavalin A (Con A) affinity chromatography, 1-D SDS-PAGE, and label-free nano-LC-MS/MS to screen biomarker candidates (serum-derived Con A-captured proteins) and then identify PTMs of validated biomarkers (serum proteins) using pooled serum from 7 RA-sSS female patients and 7 age-matched HCs (the discovery set). Furthermore, the protein level and autoantibody isotype analyses were further validated against individual serum from 18 HCs, 18 RA, 18 pSS, and 18 RA-sSS patients (the validation set). Con A-bound ITIH3 was identified and validated as the only differentially expressed protein, which was elevated. Additionally, 2 novel PTMs in ITIH3 were identified and included citrullination at arginine-(546) and arginine-(556), and hexosamine at tryptophan-(558). Further, concentrations of anti-citrullinatd-ITIH3(542-556) peptide autoantibodies significantly increased in patients with RA, pSS, and RA-sSS compared to HCs. Especially, autoantibody IgM against the citrullinated-ITIH3(542-556) peptide showed better diagnostic performance in discriminating both RA versus pSS and pSS versus RA-sSS. By using comparative proteomic analysis of serum samples, the current study discovered and validates differentially expressed Con A-bound ITIH3 as a potential biomarker for secondary Sjögren's syndrome (SS) in rheumatoid arthritis (RA) patients and healthy controls (HCs). Besides, hexosamine and citrullination on ITIH3 were further identified. Through analyzing autoantibody isotypes against the citrullinated ITIH3 peptide, patients with RA, primary SS, and RA-secondary SS, and HCs can be further discriminated. The current strategy can be applied for identifying potential diagnostic and pathologic markers for autoimmune diseases. Copyright © 2016. Published by Elsevier B.V.

Validity and reliability of haemoglobin colour scale and its comparison with clinical signs in diagnosing anaemia in pregnancy in Ahmedabad, India.

PubMed

Bala, D V; Vyas, S; Shukla, A; Tiwari, H; Bhatt, G; Gupta, K

2012-07-01

This study compared the validity of the haemoglobin colour scale (HCS) and clinical signs in diagnosing anaemia against Sahli's haemoglobinometer method as the gold standard, and assessed the reliability of HCS. The sample comprised 129 pregnant women recruited from 6 urban health centres in Ahmedabad. The prevalence of anaemia was 69.8% by Sahli's method, 78.3% by HCS and 89.9% by clinical signs; there was no statistically significant difference between Sahli's method and HCS whereas there was between Sahlis method and clinical signs. The mean haemoglobin level by Sahli's method and HCS differed significantly. The sensitivity, specificity, positive predictive value and negative predictive value of HCS was 83.3%, 33.3%, 74.3% and 46.4% respectively and that of clinical signs was 91.1%, 12.8%, 70.7% and 38.5% respectively. Interobserver agreement for HCS was moderate (K = 0.43). Clinical signs are better than HCS for diagnosing anaemia. HCS can be used in the field provided assessors are adequately trained.

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

Singh, Mahavir; Wang, Zhonghua; Cascio, Duilio

Shq1 is an essential protein involved in the early steps of biogenesis and assembly of H/ACA ribonucleoprotein particles (RNPs). Shq1 binds to dyskerin (Cbf5 in yeast) at an early step of H/ACA RNP assembly and is subsequently displaced by the H/ACA RNA. Shq1 contains an N-terminal CS and a C-terminal Shq1-specific domain (SSD). Dyskerin harbors many mutations associated with dyskeratosis congenita. Structures of yeast Shq1 SSD bound to Cbf5 revealed that only a subset of these mutations is in the SSD binding site, implicating another subset in the putative CS binding site. Here in this paper, we present the crystalmore » structure of human Shq1 CS (hCS) and the nuclear magnetic resonance (NMR) and crystal structures of hCS containing a serine substitution for proline 22 that is associated with some prostate cancers. The structure of hCS is similar to yeast Shq1 CS domain (yCS) and consists of two β-sheets that form an immunoglobulin-like β-sandwich fold. The N-terminal affinity tag sequence AHHHHHH associates with a neighboring protein in the crystal lattice to form an extra β-strand. Deletion of this tag was required to get spectra suitable for NMR structure determination, while the tag was required for crystallization. NMR chemical shift perturbation (CSP) experiments with peptides derived from putative CS binding sites on dyskerin and Cbf5 revealed a conserved surface on CS important for Cbf5/dyskerin binding. A HADDOCK (high-ambiguity-driven protein-protein docking) model of a Shq1-Cbf5 complex that defines the position of CS domain in the pre-H/ACA RNP was calculated using the CSP data.« less

Structure and Interactions of the CS Domain of Human H/ACA RNP Assembly Protein Shq1

DOE PAGES

Singh, Mahavir; Wang, Zhonghua; Cascio, Duilio; ...

2014-12-29

Shq1 is an essential protein involved in the early steps of biogenesis and assembly of H/ACA ribonucleoprotein particles (RNPs). Shq1 binds to dyskerin (Cbf5 in yeast) at an early step of H/ACA RNP assembly and is subsequently displaced by the H/ACA RNA. Shq1 contains an N-terminal CS and a C-terminal Shq1-specific domain (SSD). Dyskerin harbors many mutations associated with dyskeratosis congenita. Structures of yeast Shq1 SSD bound to Cbf5 revealed that only a subset of these mutations is in the SSD binding site, implicating another subset in the putative CS binding site. Here in this paper, we present the crystalmore » structure of human Shq1 CS (hCS) and the nuclear magnetic resonance (NMR) and crystal structures of hCS containing a serine substitution for proline 22 that is associated with some prostate cancers. The structure of hCS is similar to yeast Shq1 CS domain (yCS) and consists of two β-sheets that form an immunoglobulin-like β-sandwich fold. The N-terminal affinity tag sequence AHHHHHH associates with a neighboring protein in the crystal lattice to form an extra β-strand. Deletion of this tag was required to get spectra suitable for NMR structure determination, while the tag was required for crystallization. NMR chemical shift perturbation (CSP) experiments with peptides derived from putative CS binding sites on dyskerin and Cbf5 revealed a conserved surface on CS important for Cbf5/dyskerin binding. A HADDOCK (high-ambiguity-driven protein-protein docking) model of a Shq1-Cbf5 complex that defines the position of CS domain in the pre-H/ACA RNP was calculated using the CSP data.« less

Full impact of laboratory information system requires direct use by clinical staff: cluster randomized controlled trial.

PubMed

Blaya, Joaquín A; Shin, Sonya; Contreras, Carmen; Yale, Gloria; Suarez, Carmen; Asencios, Luis; Kim, Jihoon; Rodriguez, Pablo; Cegielski, Peter; Fraser, Hamish S F

2011-01-01

To evaluate the time to communicate laboratory results to health centers (HCs) between the e-Chasqui web-based information system and the pre-existing paper-based system. Cluster randomized controlled trial in 78 HCs in Peru. In the intervention group, 12 HCs had web access to results via e-Chasqui (point-of-care HCs) and forwarded results to 17 peripheral HCs. In the control group, 22 point-of-care HCs received paper results directly and forwarded them to 27 peripheral HCs. Baseline data were collected for 15 months. Post-randomization data were collected for at least 2 years. Comparisons were made between intervention and control groups, stratified by point-of-care versus peripheral HCs. For point-of-care HCs, the intervention group took less time to receive drug susceptibility tests (DSTs) (median 9 vs 16 days, p<0.001) and culture results (4 vs 8 days, p<0.001) and had a lower proportion of 'late' DSTs taking >60 days to arrive (p<0.001) than the control. For peripheral HCs, the intervention group had similar communication times for DST (median 22 vs 19 days, p=0.30) and culture (10 vs 9 days, p=0.10) results, as well as proportion of 'late' DSTs (p=0.57) compared with the control. Only point-of-care HCs with direct access to the e-Chasqui information system had reduced communication times and fewer results with delays of >2 months. Peripheral HCs had no benefits from the system. This suggests that health establishments should have point-of-care access to reap the benefits of electronic laboratory reporting.

Full impact of laboratory information system requires direct use by clinical staff: cluster randomized controlled trial

PubMed Central

Shin, Sonya; Contreras, Carmen; Yale, Gloria; Suarez, Carmen; Asencios, Luis; Kim, Jihoon; Rodriguez, Pablo; Cegielski, Peter; Fraser, Hamish S F

2010-01-01

Objective To evaluate the time to communicate laboratory results to health centers (HCs) between the e-Chasqui web-based information system and the pre-existing paper-based system. Methods Cluster randomized controlled trial in 78 HCs in Peru. In the intervention group, 12 HCs had web access to results via e-Chasqui (point-of-care HCs) and forwarded results to 17 peripheral HCs. In the control group, 22 point-of-care HCs received paper results directly and forwarded them to 27 peripheral HCs. Baseline data were collected for 15 months. Post-randomization data were collected for at least 2 years. Comparisons were made between intervention and control groups, stratified by point-of-care versus peripheral HCs. Results For point-of-care HCs, the intervention group took less time to receive drug susceptibility tests (DSTs) (median 9 vs 16 days, p<0.001) and culture results (4 vs 8 days, p<0.001) and had a lower proportion of ‘late’ DSTs taking >60 days to arrive (p<0.001) than the control. For peripheral HCs, the intervention group had similar communication times for DST (median 22 vs 19 days, p=0.30) and culture (10 vs 9 days, p=0.10) results, as well as proportion of ‘late’ DSTs (p=0.57) compared with the control. Conclusions Only point-of-care HCs with direct access to the e-Chasqui information system had reduced communication times and fewer results with delays of >2 months. Peripheral HCs had no benefits from the system. This suggests that health establishments should have point-of-care access to reap the benefits of electronic laboratory reporting. PMID:21113076

A High Content Screening (HCS) Assay for the Identification of Chemical Inducers of PML Oncogenic Domains (PODs)

PubMed Central

Yip, Kenneth W.; Cuddy, Michael; Pinilla, Clemencia; Giulanotti, Marc; Heynen-Genel, Susanne; Matsuzawa, Shu-ichi; Reed, John C.

2014-01-01

PML is a tumor suppressor that promotes apoptosis through both p53-dependent and - independent mechanisms, participates in Rb-mediated cell cycle arrest, inhibits neoangiogenesis, and contributes to maintenance of genomic stability. PML also plays a role in host defense against viruses, conferring antiviral activity. When active, PML localizes to subnuclear structures named PML oncogenic domains (PODs) or PML nuclear bodies (PML-NBs), whereas inactive PML is located diffusely throughout the nucleus of cells, thus providing a morphological indicator. Known activators of PML include arsenicals and interferons, however, these agents induce a plethora of toxic effects, limiting their effectiveness. The objective of the current study was to develop a high content screening (HCS) assay for the identification of chemical activators of PML. We describe methods for automated analysis of POD formation using high throughput microscopy (HTM) to localize PML immunofluorescence in conjunction with image analysis software for POD quantification. Using this HCS assay in 384 well format, we performed pilot screens of a small synthetic chemical library and mixture-based combinatorial libraries, demonstrating the robust performance of the assay. HCS counter-screening assays were also developed for hit characterization, based on immunofluorescence analyses of the subcellular location of phosphorylated H2AX or phosphorylated CHK1, which increase in a punctate nuclear pattern in response to DNA damage. Thus, the HCS assay devised here represents a high throughput screen that can be utilized to discover POD-inducing compounds that may restore the tumor suppressor activity of PML in cancers or possibly promote anti-viral states. PMID:21233309

Magnetoencephalography reveals altered auditory information processing in youth with obsessive-compulsive disorder.

PubMed

Korostenskaja, Milena; Harris, Elana; Giovanetti, Cathy; Horn, Paul; Wang, Yingying; Rose, Douglas; Fujiwara, Hisako; Xiang, Jing

2013-05-30

Patients with obsessive-compulsive disorder (OCD) often report sensory intolerances which may lead to significant functional impairment. This study used auditory evoked fields (AEFs) to address the question of whether neural correlates of sensory auditory information processing differ in youth with OCD compared with healthy comparison subjects (HCS). AEFs, recorded with a whole head 275-channel magnetoencephalography system, were elicited in response to binaural auditory stimuli from 10 pediatric subjects with OCD (ages 8-13, mean 11 years, 6 males) and 10 age- and gender-matched HCS. Three major neuromagnetic responses were studied: M70 (60-80 ms), M100 (90-120 ms), and M150 (130-190 ms). When compared with HCS, subjects with OCD demonstrated delayed latency of the M100 response. In subjects with OCD the amplitude of the M100 and M150 responses was significantly greater in the right hemisphere compared with the left hemisphere. Current results suggest that when compared with HCS, subjects with OCD have altered auditory information processing, evident from the delayed latency of the M100 response, which is thought to be associated with the encoding of physical stimulus characteristics. Interhemispheric asymmetry with increased M100 and M150 amplitudes over the right hemisphere compared with the left hemisphere was found in young OCD subjects. These results should be interpreted with caution due to the high variability rate of responses in both HCS and OCD subjects, as well as the possible effect of medication in OCD subjects. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Guideline implementation for breast healthcare in low- and middle-income countries: breast healthcare program resource allocation.

PubMed

Harford, Joe; Azavedo, Edward; Fischietto, Mary

2008-10-15

Breast cancer is serious public health problem in countries of all resource levels. Although major advances in the detection and treatment of the disease have occurred in higher income settings, similar progress has been slow or scarce in most low- and middle-income countries (LMCs). The poorer outcomes in LMCs may relate to the limited capability of their healthcare systems (HCS) to provide successful early detection, diagnosis, and treatment of breast cancer. Impediments to better outcomes include insufficient numbers of appropriately trained healthcare workers, limited access to screening/treatment facilities, inadequate supplies of necessary drugs, and timeliness of treatment after diagnosis. Clearly, these HCS deficiencies are broader than the scope of the Breast Health Global Initiative (BHGI) and are not unique to the issue of breast cancer. To address issues in HCS that hinder the delivery of breast health services, the BHGI Healthcare Systems and Public Policy Panel explored the HCS structures and function needed to operate a breast care program (BCP). Like with all BHGI guidelines, those proposed by this panel were expressed in terms of 4 strata of resource levels: basic, limited, enhanced, and maximal. The current report describes the issues and questions related to HCS that are important to consider when designing, implementing, and measuring the performance of a BCP. Health ministers, other policymakers, healthcare personnel, administrators, and anyone else involved in developing a BCP can use and adapt this framework to improve outcomes and ensure the more effective use of resources. (c) 2008 American Cancer Society.

Wnt activation followed by Notch inhibition promotes mitotic hair cell regeneration in the postnatal mouse cochlea

PubMed Central

Li, Wenyan; Chen, Yan; Zhang, Shasha; Tang, Mingliang; Sun, Shan; Chai, Renjie; Li, Huawei

2016-01-01

Hair cell (HC) loss is the main cause of permanent hearing loss in mammals. Previous studies have reported that in neonatal mice cochleae, Wnt activation promotes supporting cell (SC) proliferation and Notch inhibition promotes the trans-differentiation of SCs into HCs. However, Wnt activation alone fails to regenerate significant amounts of new HCs, Notch inhibition alone regenerates the HCs at the cost of exhausting the SC population, which leads to the death of the newly regenerated HCs. Mitotic HC regeneration might preserve the SC number while regenerating the HCs, which could be a better approach for long-term HC regeneration. We present a two-step gene manipulation, Wnt activation followed by Notch inhibition, to accomplish mitotic regeneration of HCs while partially preserving the SC number. We show that Wnt activation followed by Notch inhibition strongly promotes the mitotic regeneration of new HCs in both normal and neomycin-damaged cochleae while partially preserving the SC number. Lineage tracing shows that the majority of the mitotically regenerated HCs are derived specifically from the Lgr5+ progenitors with or without HC damage. Our findings suggest that the co-regulation of Wnt and Notch signaling might provide a better approach to mitotically regenerate HCs from Lgr5+ progenitor cells. PMID:27564256

Disrupted Brain Functional Network Architecture in Chronic Tinnitus Patients

PubMed Central

Chen, Yu-Chen; Feng, Yuan; Xu, Jin-Jing; Mao, Cun-Nan; Xia, Wenqing; Ren, Jun; Yin, Xindao

2016-01-01

Purpose: Resting-state functional magnetic resonance imaging (fMRI) studies have demonstrated the disruptions of multiple brain networks in tinnitus patients. Nonetheless, several studies found no differences in network processing between tinnitus patients and healthy controls (HCs). Its neural bases are poorly understood. To identify aberrant brain network architecture involved in chronic tinnitus, we compared the resting-state fMRI (rs-fMRI) patterns of tinnitus patients and HCs. Materials and Methods: Chronic tinnitus patients (n = 24) with normal hearing thresholds and age-, sex-, education- and hearing threshold-matched HCs (n = 22) participated in the current study and underwent the rs-fMRI scanning. We used degree centrality (DC) to investigate functional connectivity (FC) strength of the whole-brain network and Granger causality to analyze effective connectivity in order to explore directional aspects involved in tinnitus. Results: Compared to HCs, we found significantly increased network centrality in bilateral superior frontal gyrus (SFG). Unidirectionally, the left SFG revealed increased effective connectivity to the left middle orbitofrontal cortex (OFC), left posterior lobe of cerebellum (PLC), left postcentral gyrus, and right middle occipital gyrus (MOG) while the right SFG exhibited enhanced effective connectivity to the right supplementary motor area (SMA). In addition, the effective connectivity from the bilateral SFG to the OFC and SMA showed positive correlations with tinnitus distress. Conclusions: Rs-fMRI provides a new and novel method for identifying aberrant brain network architecture. Chronic tinnitus patients have disrupted FC strength and causal connectivity mostly in non-auditory regions, especially the prefrontal cortex (PFC). The current findings will provide a new perspective for understanding the neuropathophysiological mechanisms in chronic tinnitus. PMID:27458377

It still hurts: altered endogenous opioid activity in the brain during social rejection and acceptance in major depressive disorder.

PubMed

Hsu, D T; Sanford, B J; Meyers, K K; Love, T M; Hazlett, K E; Walker, S J; Mickey, B J; Koeppe, R A; Langenecker, S A; Zubieta, J-K

2015-02-01

The μ-opioid receptor (MOR) system, well known for dampening physical pain, is also hypothesized to dampen 'social pain.' We used positron emission tomography scanning with the selective MOR radioligand [(11)C]carfentanil to test the hypothesis that MOR system activation (reflecting endogenous opioid release) in response to social rejection and acceptance is altered in medication-free patients diagnosed with current major depressive disorder (MDD, n=17) compared with healthy controls (HCs, n=18). During rejection, MDD patients showed reduced endogenous opioid release in brain regions regulating stress, mood and motivation, and slower emotional recovery compared with HCs. During acceptance, only HCs showed increased social motivation, which was positively correlated with endogenous opioid release in the nucleus accumbens, a reward structure. Altered endogenous opioid activity in MDD may hinder emotional recovery from negative social interactions and decrease pleasure derived from positive interactions. Both effects may reinforce depression, trigger relapse and contribute to poor treatment outcomes.

It still hurts: altered opioid activity in the brain during social rejection and acceptance in major depressive disorder

PubMed Central

Hsu, David T; Sanford, Benjamin J; Meyers, Kortni K; Love, Tiffany M; Hazlett, Kathleen E; Walker, Sara J; Mickey, Brian J; Koeppe, Robert A; Langenecker, Scott A; Zubieta, Jon-Kar

2015-01-01

The μ-opioid receptor (MOR) system, well known for dampening physical pain, is also hypothesized to dampen “social pain.” We used positron emission tomography scanning with the selective MOR radioligand [11C]carfentanil to test the hypothesis that MOR system activation in response to social rejection and acceptance is altered in medication-free patients diagnosed with current major depressive disorder (MDD, n = 17) compared to healthy controls (HCs, n = 18). During rejection, MDD patients showed reduced MOR activation (e.g., reduced endogenous opioid release) in brain regions regulating stress, mood, and motivation, and slower emotional recovery compared to HCs. During acceptance, only HCs showed increased social motivation, which was positively correlated with MOR activation in the nucleus accumbens, a reward structure. Abnormal MOR function in MDD may hinder emotional recovery from negative social interactions and decrease pleasure derived from positive interactions. Both effects may reinforce depression, trigger relapse, and contribute to poor treatment outcomes. PMID:25600108

Are transversal MR images sufficient to distinguish persons with mild cognitive impairment from healthy controls?

PubMed

Mönninghoff, Christoph; Dlugaj, Martha; Kraff, Oliver; Geisel, Marie Henrike; Jöckel, Karl-Heinz; Erbel, Raimund; Weimar, Christian; Wanke, Isabel

2015-09-01

Mild cognitive impairment (MCI) is associated with an increased risk of developing dementia. This study aims to determine whether current standard magnetic resonance imaging (MRI) is providing markers that can distinguish between subjects with amnestic MCI (aMCI), nonamnestic MCI (naMCI), and healthy controls (HCs). A subset of 126 MCI subjects and 126 age-, gender-, and education-appropriate HCs (mean age, 70.9 years) were recruited from 4157 participants in the longitudinal community-based Heinz Nixdorf Recall Study. The burden of white matter hyperintensities (WMHs), cerebral microbleeds, and brain atrophy was evaluated on transversal MR images from a single 1.5-T MR scanner by two blinded neuroradiologists. Logistic regression and receiver-operating characteristic analysis were used for statistical analysis. Occipital WMH burden was significantly increased in aMCI, but not in naMCI relative to HCs (P = .01). The combined MCI group showed brain atrophy relative to HCs (P = .01) pronounced at caudate nuclei (P = .01) and temporal horn level (P = .004) of aMCI patients and increased at the frontal and occipital horns of naMCI patients compared to either aMCI or HCs. Microbleeds were equally distributed in the MCI and control group, but more frequent in aMCI (22 of 84) compared to naMCI subjects (3 of 23). In his cohort, increased occipital WMHs and cortical and subcortical brain atrophies at temporal horn and caudate nuclei level distinguished aMCI from naMCI subjects and controls. Volumetric indices appear of interest and should be assessed under reproducible conditions to gain diagnostic accuracy. Copyright © 2015 AUR. Published by Elsevier Inc. All rights reserved.

HCS road: an enterprise system for integrated HCS data management and analysis.

PubMed

Jackson, Donald; Lenard, Michael; Zelensky, Alexander; Shaikh, Mohammad; Scharpf, James V; Shaginaw, Richard; Nawade, Mahesh; Agler, Michele; Cloutier, Normand J; Fennell, Myles; Guo, Qi; Wardwell-Swanson, Judith; Zhao, Dandan; Zhu, Yingjie; Miller, Christopher; Gill, James

2010-08-01

The effective analysis and interpretation of high-content screening (HCS) data requires joining results to information on experimental treatments and controls, normalizing data, and selecting hits or fitting concentration-response curves. HCS data have unique requirements that are not supported by traditional high-throughput screening databases, including the ability to designate separate positive and negative controls for different measurements in multiplexed assays; the ability to capture information on the cell lines, fluorescent reagents, and treatments in each assay; the ability to store and use individual-cell and image data; and the ability to support HCS readers and software from multiple vendors along with third-party image analysis tools. To address these requirements, the authors developed an enterprise system for the storage and processing of HCS images and results. This system, HCS Road, supports target identification, lead discovery, lead evaluation, and lead profiling activities. A dedicated client supports experimental design, data review, and core analyses and displays images together with results for assay development, hit assessment, and troubleshooting. Data can be exported to third-party applications for further analysis and exploration. HCS Road provides a single source for high-content results across the organization, regardless of the group or instrument that produced them.

Intelligent Interfaces for Mining Large-Scale RNAi-HCS Image Databases

PubMed Central

Lin, Chen; Mak, Wayne; Hong, Pengyu; Sepp, Katharine; Perrimon, Norbert

2010-01-01

Recently, High-content screening (HCS) has been combined with RNA interference (RNAi) to become an essential image-based high-throughput method for studying genes and biological networks through RNAi-induced cellular phenotype analyses. However, a genome-wide RNAi-HCS screen typically generates tens of thousands of images, most of which remain uncategorized due to the inadequacies of existing HCS image analysis tools. Until now, it still requires highly trained scientists to browse a prohibitively large RNAi-HCS image database and produce only a handful of qualitative results regarding cellular morphological phenotypes. For this reason we have developed intelligent interfaces to facilitate the application of the HCS technology in biomedical research. Our new interfaces empower biologists with computational power not only to effectively and efficiently explore large-scale RNAi-HCS image databases, but also to apply their knowledge and experience to interactive mining of cellular phenotypes using Content-Based Image Retrieval (CBIR) with Relevance Feedback (RF) techniques. PMID:21278820

Revisiting Peruvian anchovy ( Engraulis ringens) trophodynamics provides a new vision of the Humboldt Current system

NASA Astrophysics Data System (ADS)

Espinoza, Pepe; Bertrand, Arnaud

2008-10-01

The Peruvian anchovy or anchoveta ( Engraulis ringens) forages on plankton and is a main prey for marine mammals, seabirds, fish, and fishers, and is therefore a key element of the food web in the Humboldt Current system (HCS). Here, we present results from the analysis of 21,203 anchoveta stomach contents sampled during 23 acoustic surveys over the period 1996-2003. Prey items were identified to the genus level, and the relative dietary importance of different prey was assessed by determination of their carbon content. Variability in stomach fullness was examined relative to the diel cycle, the distance from the coast, sea surface temperature, and latitude, using generalized additive models (GAMs). Whereas phytoplankton largely dominated anchoveta diets in terms of numerical abundance and comprised >99% of ingested prey items, the carbon content of prey items indicated that zooplankton was by far the most important dietary component, with euphausiids contributing 67.5% of dietary carbon followed by copepods (26.3%). Stomach fullness data showed that anchoveta feed mainly during daytime between 07h00 and 18h00, although night-time feeding also made a substantial contribution to total food consumption. Stomach fullness also varied with latitude, distance from the coast, and temperature, but with substantial variability indicating a high degree of plasticity in anchoveta feeding behaviour. The results suggest an ecological role for anchoveta that challenges current understanding of its position in the foodweb, the functioning of the HCS, and trophic models of the HCS.

Decreased empathy response to other people's pain in bipolar disorder: evidence from an event-related potential study.

PubMed

Yang, Jingyue; Hu, Xinglong; Li, Xiaosi; Zhang, Lei; Dong, Yi; Li, Xiang; Zhu, Chunyan; Xie, Wen; Mu, Jingjing; Yuan, Su; Chen, Jie; Chen, Fangfang; Yu, Fengqiong; Wang, Kai

2017-01-06

Bipolar disorder (BD) patients often demonstrate poor socialization that may stem from a lower capacity for empathy. We examined the associated neurophysiological abnormalities by comparing event-related potentials (ERP) between 30 BD patients in different states and 23 healthy controls (HCs, matched for age, sex, and education) during a pain empathy task. Subjects were presented pictures depicting pain or neutral images and asked to judge whether the person shown felt pain (pain task) and to identify the affected side (laterality task) during ERP recording. Amplitude of pain-empathy related P3 (450-550 ms) of patients versus HCs was reduced in painful but not neutral conditions in occipital areas [(mean (95% confidence interval), BD vs. HCs: 4.260 (2.927, 5.594) vs. 6.396 (4.868, 7.924)] only in pain task. Similarly, P3 (550-650 ms) was reduced in central areas [4.305 (3.029, 5.581) vs. 6.611 (5.149, 8.073)]. Current source density in anterior cingulate cortex differed between pain-depicting and neutral conditions in HCs but not patients. Manic severity was negatively correlated with P3 difference waves (pain - neutral) in frontal and central areas (Pearson r = -0.497, P = 0.005; r = -0.377, P = 0.040). Electrophysiological correlates of empathy processing are reduced in BD depending on manic symptom severity.

Outcomes of antiretroviral treatment programmes in rural Lesotho: health centres and hospitals compared

PubMed Central

Labhardt, Niklaus Daniel; Keiser, Olivia; Sello, Motlalepula; Lejone, Thabo Ishmael; Pfeiffer, Karolin; Davies, Mary-Ann; Egger, Matthias; Ehmer, Jochen; Wandeler, Gilles

2013-01-01

Introduction Lesotho was among the first countries to adopt decentralization of care from hospitals to nurse-led health centres (HCs) to scale up the provision of antiretroviral therapy (ART). We compared outcomes between patients who started ART at HCs and hospitals in two rural catchment areas in Lesotho. Methods The two catchment areas comprise two hospitals and 12 HCs. Patients ≥16 years starting ART at a hospital or HC between 2008 and 2011 were included. Loss to follow-up (LTFU) was defined as not returning to the facility for ≥180 days after the last visit, no follow-up (no FUP) as not returning after starting ART, and retention in care as alive and on ART at the facility. The data were analysed using logistic regression, competing risk regression and Kaplan-Meier methods. Multivariable analyses were adjusted for sex, age, CD4 cell count, World Health Organization stage, catchment area and type of ART. All analyses were stratified by gender. Results Of 3747 patients, 2042 (54.5%) started ART at HCs. Both women and men at hospitals had more advanced clinical and immunological stages of disease than those at HCs. Over 5445 patient-years, 420 died and 475 were LTFU. Kaplan-Meier estimates for three-year retention were 68.7 and 69.7% at HCs and hospitals, respectively, among women (p=0.81) and 68.8% at HCs versus 54.7% at hospitals among men (p<0.001). These findings persisted in adjusted analyses, with similar retention at HCs and hospitals among women (odds ratio (OR): 0.89, 95% confidence interval (CI): 0.73–1.09) and higher retention at HCs among men (OR: 1.53, 95% CI: 1.20–1.96). The latter result was mainly driven by a lower proportion of patients LTFU at HCs (OR: 0.68, 95% CI: 0.51–0.93). Conclusions In rural Lesotho, overall retention in care did not differ significantly between nurse-led HCs and hospitals. However, men seemed to benefit most from starting ART at HCs, as they were more likely to remain in care in these facilities compared to hospitals. PMID:24267671

Outcomes of antiretroviral treatment programmes in rural Lesotho: health centres and hospitals compared.

PubMed

Labhardt, Niklaus Daniel; Keiser, Olivia; Sello, Motlalepula; Lejone, Thabo Ishmael; Pfeiffer, Karolin; Davies, Mary-Ann; Egger, Matthias; Ehmer, Jochen; Wandeler, Gilles

2013-11-21

Lesotho was among the first countries to adopt decentralization of care from hospitals to nurse-led health centres (HCs) to scale up the provision of antiretroviral therapy (ART). We compared outcomes between patients who started ART at HCs and hospitals in two rural catchment areas in Lesotho. The two catchment areas comprise two hospitals and 12 HCs. Patients ≥16 years starting ART at a hospital or HC between 2008 and 2011 were included. Loss to follow-up (LTFU) was defined as not returning to the facility for ≥180 days after the last visit, no follow-up (no FUP) as not returning after starting ART, and retention in care as alive and on ART at the facility. The data were analysed using logistic regression, competing risk regression and Kaplan-Meier methods. Multivariable analyses were adjusted for sex, age, CD4 cell count, World Health Organization stage, catchment area and type of ART. All analyses were stratified by gender. Of 3747 patients, 2042 (54.5%) started ART at HCs. Both women and men at hospitals had more advanced clinical and immunological stages of disease than those at HCs. Over 5445 patient-years, 420 died and 475 were LTFU. Kaplan-Meier estimates for three-year retention were 68.7 and 69.7% at HCs and hospitals, respectively, among women (p=0.81) and 68.8% at HCs versus 54.7% at hospitals among men (p<0.001). These findings persisted in adjusted analyses, with similar retention at HCs and hospitals among women (odds ratio (OR): 0.89, 95% confidence interval (CI): 0.73-1.09) and higher retention at HCs among men (OR: 1.53, 95% CI: 1.20-1.96). The latter result was mainly driven by a lower proportion of patients LTFU at HCs (OR: 0.68, 95% CI: 0.51-0.93). In rural Lesotho, overall retention in care did not differ significantly between nurse-led HCs and hospitals. However, men seemed to benefit most from starting ART at HCs, as they were more likely to remain in care in these facilities compared to hospitals.

The Hajdu Cheney Mutation Is a Determinant of B-Cell Allocation of the Splenic Marginal Zone.

PubMed

Yu, Jungeun; Zanotti, Stefano; Walia, Bhavita; Jellison, Evan; Sanjay, Archana; Canalis, Ernesto

2018-01-01

The neurogenic locus notch homolog protein (Notch)-2 receptor is a determinant of B-cell allocation, and gain-of-NOTCH2-function mutations are associated with Hajdu-Cheney syndrome (HCS), a disease presenting with osteoporosis and acro-osteolysis. We generated a mouse model reproducing the HCS mutation (Notch2HCS), and heterozygous global mutant mice displayed gain-of-Notch2 function. In the mutant spleen, the characteristic perifollicular rim marking the marginal zone (MZ), which is the interface between the nonlymphoid red pulp and the lymphoid white pulp, merged with components of the white pulp. As a consequence, the MZ of Notch2HCS mice occupied most of the splenic structure. To explore the mechanisms involved, lymphocyte populations from the bone marrow and spleen were harvested from heterozygous Notch2HCS mice and sex-matched control littermates and analyzed by flow cytometry. Notch2HCS mice had an increase in CD21/35 high CD23 - splenic MZ B cells of approximately fivefold and a proportional decrease in splenic follicular B cells (CD21/35 int CD23 + ) at 1, 2, and 12 months of age. Western blot analysis revealed that Notch2HCS mutant splenocytes had increased phospho-Akt and phospho-Jun N-terminal kinase, and gene expression analysis of splenic CD19 + B cells demonstrated induction of Hes1 and Hes5 in Notch2HCS mutants. Anti-Notch2 antibodies decreased MZ B cells in control and Notch2HCS mice. In conclusion, Notch2HCS mutant mice have increased mature B cells in the MZ of the spleen. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Complexity of gap junctions between horizontal cells of the carp retina.

PubMed

Greb, H; Hermann, S; Dirks, P; Ommen, G; Kretschmer, V; Schultz, K; Zoidl, G; Weiler, R; Janssen-Bienhold, U

2017-01-06

In the vertebrate retina, horizontal cells (HCs) reveal homologous coupling by gap junctions (gj), which are thought to consist of different connexins (Cx). However, recent studies in mouse, rabbit and zebrafish retina indicate that individual HCs express more than one connexin. To provide further insights into the composition of gj connecting HCs and to determine whether HCs express multiple connexins, we examined the molecular identity and distribution of gj between HCs of the carp retina. We have cloned four carp connexins designated Cx49.5, Cx55.5, Cx52.6 and Cx53.8 with a close relationship to connexins previously reported in HCs of mouse, rabbit and zebrafish, respectively. Using in situ hybridization, Cx49.5 expression was detected in different subpopulations of retinal neurons including HCs, whereas the Cx52.6 transcript was localized exclusively in HCs. Using specific antibodies, Cx55.5 and Cx53.8 were detected on dendrites of all four HC subtypes and axon terminals. Immunoelectron microscopy confirmed the presence of Cx55.5 and Cx53.8 in gap junctions between these processes and Cx55.5 was additionally observed in HC dendrites invaginating cone pedicles, suggesting its participation in the modulation of photoreceptor output in the carp retina. Furthermore, using single-cell RT-PCR, all four connexins were detected in different subtypes of HCs, suggesting overlapping expression patterns. Thus, the composition of gj mediating homologous coupling between subtypes of carp HCs appears to be more complex than expected. Moreover, BLAST searches of the preliminary carp genome, using novel sequences as query, suggest that most of the analyzed connexin genes are duplicated in carp. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Sources of protons and a role for bicarbonate in inhibitory feedback from horizontal cells to cones in Ambystoma tigrinum retina.

PubMed

Warren, Ted J; Van Hook, Matthew J; Supuran, Claudiu T; Thoreson, Wallace B

2016-11-15

In the vertebrate retina, photoreceptors influence the signalling of neighbouring photoreceptors through lateral-inhibitory interactions mediated by horizontal cells (HCs). These interactions create antagonistic centre-surround receptive fields important for detecting edges and generating chromatically opponent responses in colour vision. The mechanisms responsible for inhibitory feedback from HCs involve changes in synaptic cleft pH that modulate photoreceptor calcium currents. However, the sources of synaptic protons involved in feedback and the mechanisms for their removal from the cleft when HCs hyperpolarize to light remain unknown. Our results indicate that Na + -H + exchangers are the principal source of synaptic cleft protons involved in HC feedback but that synaptic cleft alkalization during light-evoked hyperpolarization of HCs also involves changes in bicarbonate transport across the HC membrane. In addition to delineating processes that establish lateral inhibition in the retina, these results contribute to other evidence showing the key role for pH in regulating synaptic signalling throughout the nervous system. Lateral-inhibitory feedback from horizontal cells (HCs) to photoreceptors involves changes in synaptic cleft pH accompanying light-evoked changes in HC membrane potential. We analysed HC to cone feedback by studying surround-evoked light responses of cones and by obtaining paired whole cell recordings from cones and HCs in salamander retina. We tested three potential sources for synaptic cleft protons: (1) generation by extracellular carbonic anhydrase (CA), (2) release from acidic synaptic vesicles and (3) Na + /H + exchangers (NHEs). Neither antagonizing extracellular CA nor blocking loading of protons into synaptic vesicles eliminated feedback. However, feedback was eliminated when extracellular Na + was replaced with choline and significantly reduced by an NHE inhibitor, cariporide. Depriving NHEs of intracellular protons by buffering HC cytosol with a pH 9.2 pipette solution eliminated feedback, whereas alkalinizing the cone cytosol did not, suggesting that HCs are a major source for protons in feedback. We also examined mechanisms for changing synaptic cleft pH in response to changes in HC membrane potential. Increasing the trans-membrane proton gradient by lowering the extracellular pH from 7.8 to 7.4 to 7.1 strengthened feedback. While maintaining constant extracellular pH with 1 mm HEPES, removal of bicarbonate abolished feedback. Elevating intracellular bicarbonate levels within HCs prevented this loss of feedback. A bicarbonate transport inhibitor, 4,4'-diisothiocyano-2,2'-stilbenedisulfonic acid (DIDS), also blocked feedback. Together, these results suggest that NHEs are the primary source of extracellular protons in HC feedback but that changes in cleft pH accompanying changes in HC membrane voltage also require bicarbonate flux across the HC membrane. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Sources of protons and a role for bicarbonate in inhibitory feedback from horizontal cells to cones in Ambystoma tigrinum retina

PubMed Central

Warren, Ted J.; Van Hook, Matthew J.; Supuran, Claudiu T.

2016-01-01

Key points In the vertebrate retina, photoreceptors influence the signalling of neighbouring photoreceptors through lateral‐inhibitory interactions mediated by horizontal cells (HCs). These interactions create antagonistic centre‐surround receptive fields important for detecting edges and generating chromatically opponent responses in colour vision.The mechanisms responsible for inhibitory feedback from HCs involve changes in synaptic cleft pH that modulate photoreceptor calcium currents. However, the sources of synaptic protons involved in feedback and the mechanisms for their removal from the cleft when HCs hyperpolarize to light remain unknown.Our results indicate that Na+–H+ exchangers are the principal source of synaptic cleft protons involved in HC feedback but that synaptic cleft alkalization during light‐evoked hyperpolarization of HCs also involves changes in bicarbonate transport across the HC membrane.In addition to delineating processes that establish lateral inhibition in the retina, these results contribute to other evidence showing the key role for pH in regulating synaptic signalling throughout the nervous system. Abstract Lateral‐inhibitory feedback from horizontal cells (HCs) to photoreceptors involves changes in synaptic cleft pH accompanying light‐evoked changes in HC membrane potential. We analysed HC to cone feedback by studying surround‐evoked light responses of cones and by obtaining paired whole cell recordings from cones and HCs in salamander retina. We tested three potential sources for synaptic cleft protons: (1) generation by extracellular carbonic anhydrase (CA), (2) release from acidic synaptic vesicles and (3) Na+/H+ exchangers (NHEs). Neither antagonizing extracellular CA nor blocking loading of protons into synaptic vesicles eliminated feedback. However, feedback was eliminated when extracellular Na+ was replaced with choline and significantly reduced by an NHE inhibitor, cariporide. Depriving NHEs of intracellular protons by buffering HC cytosol with a pH 9.2 pipette solution eliminated feedback, whereas alkalinizing the cone cytosol did not, suggesting that HCs are a major source for protons in feedback. We also examined mechanisms for changing synaptic cleft pH in response to changes in HC membrane potential. Increasing the trans‐membrane proton gradient by lowering the extracellular pH from 7.8 to 7.4 to 7.1 strengthened feedback. While maintaining constant extracellular pH with 1 mm HEPES, removal of bicarbonate abolished feedback. Elevating intracellular bicarbonate levels within HCs prevented this loss of feedback. A bicarbonate transport inhibitor, 4,4′‐diisothiocyano‐2,2′‐stilbenedisulfonic acid (DIDS), also blocked feedback. Together, these results suggest that NHEs are the primary source of extracellular protons in HC feedback but that changes in cleft pH accompanying changes in HC membrane voltage also require bicarbonate flux across the HC membrane. PMID:27345444

High-content screening in microfluidic devices.

PubMed

Cheong, Raymond; Paliwal, Saurabh; Levchenko, Andre

2010-08-01

Miniaturization is the key to advancing the state of the art in high-content screening (HCS) in order to enable dramatic cost savings through reduced usage of expensive biochemical reagents and to enable large-scale screening on primary cells. Microfluidic technology offers the potential to enable HCS to be performed with an unprecedented degree of miniaturization. This perspective highlights a real-world example from the authors’ work of HCS assays implemented in a highly miniaturized microfluidic format. The advantages of this technology are discussed, including cost savings, high-throughput screening on primary cells, improved accuracy, the ability to study complex time-varying stimuli, and ease of automation, integration and scaling. The reader will understand the capabilities of anew microfluidics-based platform for HCS and the advantages it provides over conventional plate-based HCS. Microfluidics technology will drive significant advancements and broader usage and applicability of HCS in drug discovery.

Detecting nuclear materials smuggling: performance evaluation of container inspection policies.

PubMed

Gaukler, Gary M; Li, Chenhua; Ding, Yu; Chirayath, Sunil S

2012-03-01

In recent years, the United States, along with many other countries, has significantly increased its detection and defense mechanisms against terrorist attacks. A potential attack with a nuclear weapon, using nuclear materials smuggled into the country, has been identified as a particularly grave threat. The system for detecting illicit nuclear materials that is currently in place at U.S. ports of entry relies heavily on passive radiation detectors and a risk-scoring approach using the automated targeting system (ATS). In this article we analyze this existing inspection system and demonstrate its performance for several smuggling scenarios. We provide evidence that the current inspection system is inherently incapable of reliably detecting sophisticated smuggling attempts that use small quantities of well-shielded nuclear material. To counter the weaknesses of the current ATS-based inspection system, we propose two new inspection systems: the hardness control system (HCS) and the hybrid inspection system (HYB). The HCS uses radiography information to classify incoming containers based on their cargo content into "hard" or "soft" containers, which then go through different inspection treatment. The HYB combines the radiography information with the intelligence information from the ATS. We compare and contrast the relative performance of these two new inspection systems with the existing ATS-based system. Our studies indicate that the HCS and HYB policies outperform the ATS-based policy for a wide range of realistic smuggling scenarios. We also examine the impact of changes in adversary behavior on the new inspection systems and find that they effectively preclude strategic gaming behavior of the adversary. © 2011 Society for Risk Analysis.

Comprehension of hazard communication: effects of pictograms on safety data sheets and labels.

PubMed

Boelhouwer, Eric; Davis, Jerry; Franco-Watkins, Ana; Dorris, Nathan; Lungu, Claudiu

2013-09-01

The United Nations has proposed the Globally Harmonized System (GHS) of Classification and Labelling of Chemicals to make hazard communication more uniform and to improve comprehension. Two experiments were conducted to test whether the addition of hazard and precautionary pictograms to safety data sheets and product labels would improve the transfer of information to users compared to safety data sheets and product labels containing text only. Additionally, naïve users, workers, and experts were tested to determine any potential differences among users. The effect of adding pictograms to safety data sheets and labels was statistically significant for some conditions, but was not significant across all conditions. One benefit of the addition of pictograms was that the time to respond to the survey questions decreased when the pictograms were present for both the SDS and the labels. GHS format SDS and labels do provide benefits to users, but the system will need further enhancements and modifications to continue to improve the effectiveness of hazard communication. The final rule to modify the HCS to include the Globally Harmonized System (GHS) for the Classification and Labelling of Chemicals announced by OSHA (2012b) will change the information content of every chemical SDS and label used in commerce. This study suggests that the inclusion of GHS hazard pictograms and precautionary pictograms to SDS and labels may benefit the user. Copyright © 2013 National Safety Council and Elsevier Ltd. All rights reserved.

Agent-Based Computational Modeling to Examine How Individual Cell Morphology Affects Dosimetry

EPA Science Inventory

Cell-based models utilizing high-content screening (HCS) data have applications for predictive toxicology. Evaluating concentration-dependent effects on cell fate and state response is a fundamental utilization of HCS data.Although HCS assays may capture quantitative readouts at ...

Comparison of human chorionic somatomammotropin (HCS) standards for radioimmunoassay

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

Cocola, F.; Genazzani, A.R.; Neri, P.

1973-01-01

A comparison was made between four commercially available HCS standards for radioimmunoassay, an interim standard from the Division of Biological Standards of the Medical Research Council. and a new preparation from our laboratories. Many differences are found between the various HCS preparations tested, and this may be one reason for the discrepancies found in absolute HCS plasma levels reported by different authors. The new Sclavo preparation seems to be the best, and its use is proposed as a new standard for radioimmunoassay. (auth)

Population-based home care services in breast cancer: utilization and costs

PubMed Central

Mittmann, N.; Isogai, P.K.; Saskin, R.; Liu, N.; Porter, J.M.; Cheung, M.C.; Leighl, N.B.; Hoch, J.S.; Trudeau, M.E.; Evans, W.K.; Dainty, K.N.; Earle, C.C.

2012-01-01

Objective To determine utilization and costs of home care services (hcs) for individuals with a diagnosis of breast cancer (bc). Methods Incident cases of invasive bc in women were extracted from the Ontario Cancer Registry (2005–2009) and linked with other Ontario health care administrative databases. Control patients were selected from the population of women never diagnosed with any type of cancer. The types and proportions of hcs used were determined and stratified by disease stage. Attributable home care utilization and costs for bc patients were determined. Factors associated with hcs costs were assessed using regression analysis. Results Among the 39,656 bc and 198,280 control patients identified (median age: 61.6 years for both), 75.4% of bc patients used hcs (62.1% stage i; 85.7% stage ii; 94.6% stage iii; 79.1% stage iv) compared with 14.6% of control patients. The number of hcs used per patient–year were significantly higher for the bc patients than for the control patients (14.97 vs. 6.13, p < 0.01), resulting in higher costs per patient–year ($1,210 vs. $325; $885 attributable cost to bc, p < 0.01). The number of hcs utilized and the associated costs increased as the bc stage increased. In contrast, hcs costs decreased as income increased and as previous health care exposure decreased. Interpretation Patients with bc used twice as many hcs, resulting in costs that were almost 4 times those observed in a matched control group. Less than an additional $1000 per bc patient per year were spent on hcs utilization in the study population. PMID:23300362

Directional selectivity of afferent neurons in zebrafish neuromasts is regulated by Emx2 in presynaptic hair cells

PubMed Central

Ji, Young Rae; Warrier, Sunita; Jiang, Tao

2018-01-01

The orientation of hair bundles on top of sensory hair cells (HCs) in neuromasts of the lateral line system allows fish to detect direction of water flow. Each neuromast shows hair bundles arranged in two opposing directions and each afferent neuron innervates only HCs of the same orientation. Previously, we showed that this opposition is established by expression of Emx2 in half of the HCs, where it mediates hair bundle reversal (Jiang et al., 2017). Here, we show that Emx2 also regulates neuronal selection: afferent neurons innervate either Emx2-positive or negative HCs. In emx2 knockout and gain-of-function neuromasts, all HCs are unidirectional and the innervation patterns and physiological responses of the afferent neurons are dependent on the presence or absence of Emx2. Our results indicate that Emx2 mediates the directional selectivity of neuromasts by two distinct processes: regulating hair bundle orientation in HCs and selecting afferent neuronal targets. PMID:29671737

High content screening in microfluidic devices

PubMed Central

Cheong, Raymond; Paliwal, Saurabh; Levchenko, Andre

2011-01-01

Importance of the field Miniaturization is key to advancing the state-of-the-art in high content screening (HCS), in order to enable dramatic cost savings through reduced usage of expensive biochemical reagents and to enable large-scale screening on primary cells. Microfluidic technology offers the potential to enable HCS to be performed with an unprecedented degree of miniaturization. Areas covered in this review This perspective highlights a real-world example from the authors’ work of HCS assays implemented in a highly miniaturized microfluidic format. Advantages of this technology are discussed, including cost savings, high throughput screening on primary cells, improved accuracy, the ability to study complex time-varying stimuli, and ease of automation, integration, and scaling. What the reader will gain The reader will understand the capabilities of a new microfluidics-based platform for HCS, and the advantages it provides over conventional plate-based HCS. Take home message Microfluidics technology will drive significant advancements and broader usage and applicability of HCS in drug discovery. PMID:21852997

Lgr5+ Cells Regenerate Hair Cells via Proliferation and Direct Transdifferentiation in Damaged Neonatal Mouse Utricle

PubMed Central

Wang, Tian; Chai, Renjie; Kim, Grace S.; Pham, Nicole; Jansson, Lina; Nguyen, Duc-Huy; Kuo, Bryan; May, Lindsey; Zuo, Jian; Cunningham, Lisa L.; Cheng, Alan G.

2015-01-01

Recruitment of endogenous progenitors is critical during tissue repair. The inner ear utricle requires mechanosensory hair cells (HCs) to detect linear acceleration. After damage, non-mammalian utricles regenerate HCs via both proliferation and direct transdifferentiation. In adult mammals, limited transdifferentiation from unidentified progenitors occurs to regenerate extrastriolar Type II HCs. Here, we show that HC damage in neonatal mouse utricle activates the Wnt target gene Lgr5 in striolar supporting cells. Lineage tracing and time-lapse microscopy reveal that Lgr5+ cells transdifferentiate into HC-like cells in vitro. In contrast to adults, HC ablation in neonatal utricles in vivo recruits Lgr5+ cells to regenerate striolar HCs through mitotic and transdifferentiation pathways. Both Type I and II HCs are regenerated, and regenerated HCs display stereocilia and synapses. Lastly, stabilized β-catenin in Lgr5+ cells enhances mitotic activity and HC regeneration. Thus Lgr5 marks Wnt-regulated, damage-activated HC progenitors and may help uncover factors driving mammalian HC regeneration. PMID:25849379

Prediction of Advisability of Returning Home Using the Home Care Score

PubMed Central

Matsugi, Akiyoshi; Tani, Keisuke; Tamaru, Yoshiki; Yoshioka, Nami; Yamashita, Akira; Mori, Nobuhiko; Oku, Kosuke; Ikeda, Masashi; Nagano, Kiyoshi

2015-01-01

Purpose. The aim of this study was to assess whether the home care score (HCS), which was developed by the Ministry of Health and Welfare in Japan in 1992, is useful for the prediction of advisability of home care. Methods. Subjects living at home and in assisted-living facilities were analyzed. Binominal logistic regression analyses, using age, sex, the functional independence measure score, and the HCS, along with receiver operating characteristic curve analyses, were conducted. Findings/Conclusions. Only HCS was selected for the regression equation. Receiver operating characteristic curve analysis revealed that the area under the curve (0.9), sensitivity (0.82), specificity (0.83), and positive predictive value (0.84) for HCS were higher than those for the functional independence measure, indicating that the HCS is a powerful predictor for advisability of home care. Clinical Relevance. Comprehensive measurements of the condition of provided care and the activities of daily living of the subjects, which are included in the HCS, are required for the prediction of advisability of home care. PMID:26491568

Substrates of neuropsychological functioning in stimulant dependence: a review of functional neuroimaging research

PubMed Central

Crunelle, Cleo L; Veltman, Dick J; Booij, Jan; Emmerik – van Oortmerssen, Katelijne; den Brink, Wim

2012-01-01

Stimulant dependence is associated with neuropsychological impairments. Here, we summarize and integrate the existing neuroimaging literature on the neural substrates of neuropsychological (dys)function in stimulant dependence, including cocaine, (meth-)amphetamine, ecstasy and nicotine dependence, and excessive caffeine use, comparing stimulant abusers (SAs) to nondrug using healthy controls (HCs). Despite some inconsistencies, most studies indicated altered brain activation in prefrontal cortex (PFC) and insula in response to reward and punishment, and higher limbic and anterior cingulate cortex (ACC)/PFC activation during craving and attentional bias paradigms in SAs compared with HCs. Impulsivity in SAs was associated with lower ACC and presupplementary motor area activity compared with HCs, and related to both ventral (amygdala, ventrolateral PFC, insula) and dorsal (dorsolateral PFC, dorsal ACC, posterior parietal cortex) systems. Decision making in SAs was associated with low dorsolateral PFC activity and high orbitofrontal activity. Finally, executive function in SAs was associated with lower activation in frontotemporal regions and higher activation in premotor cortex compared with HCs. It is concluded that the lower activations compared with HCs are likely to reflect the neural substrate of impaired neurocognitive functions, whereas higher activations in SAs compared with HCs are likely to reflect compensatory cognitive control mechanisms to keep behavioral task performance to a similar level as in HCs. However, before final conclusions can be drawn, additional research is needed using neuroimaging in SAs and HCs using larger and more homogeneous samples as well as more comparable task paradigms, study designs, and statistical analyses. PMID:22950052

Disease-Related Microstructural Differences in the Brain in Women With Provoked Vestibulodynia.

PubMed

Gupta, Arpana; Woodworth, Davis C; Ellingson, Benjamin M; Rapkin, Andrea J; Naliboff, Bruce; Kilpatrick, Lisa A; Stains, Jean; Masghati, Salome; Tillisch, Kirsten; Mayer, Emeran A; Labus, Jennifer S

2018-05-01

Provoked vestibulodynia (PVD) is a chronic pelvic pain disorder affecting 16% of the female population. Neuroimaging studies have highlighted central abnormalities in PVD, similar to other chronic pelvic pain disorders, including brain regions involved in sensory processing and modulation of pain. The aim of the study was to determine alterations in the subvoxel, microstructural organization within tissues in PVD compared with healthy control participants (HCs) and a disease control group (irritable bowel syndrome [IBS]). Diffusion tensor imaging magnetic resonance imaging was conducted in 87 age-matched premenopausal women (29 PVD, 29 HCs, 29 IBS). Statistical parameter mapping of fractional anisotropy (FA) and mean diffusivity (MD) maps were used to identify microstructural difference in the brain specific to PVD or shared with IBS. PVD alterations in microstructural organization of the brain were predominantly observed in fibers associated with sensorimotor integration and pain processing that relay information between the thalamus, basal ganglia, sensorimotor, and insular cortex. PVD, compared with HCs, showed extensive increases in the FA of somatosensory and basal ganglia regions. In contrast, PVD and IBS subjects did not show any FA-related group differences. PVD subjects showed greater MD in the basal ganglia compared with HCs (higher MD in the internal capsule and pallidum) and IBS (higher MD in the putamen and pallidum). Increases in MD were associated with increased vaginal muscle tenderness and vulvar pain. The current findings highlight possible shared mechanisms between 2 different pelvic pain disorders, but also highlight the widespread alterations observed specifically in PVD compared with HCs. Alterations in microstructure in PVD were observed in fibers associated with sensorimotor integration and pain processing, which were also associated with increased vaginal muscle tenderness and vulvar pain. These alterations may be contributing to increased pain sensitivity and tenderness, highlighting the need for new therapies targeting the central nervous system. Copyright © 2018 The American Pain Society. Published by Elsevier Inc. All rights reserved.

Irreversible Heavy Chain Transfer to Chondroitin*

PubMed Central

Lauer, Mark E.; Hascall, Vincent C.; Green, Dixy E.; DeAngelis, Paul L.; Calabro, Anthony

2014-01-01

We have recently demonstrated that the transfer of heavy chains (HCs) from inter-α-inhibitor, via the enzyme TSG-6 (tumor necrosis factor-stimulated gene 6), to hyaluronan (HA) oligosaccharides is an irreversible event in which subsequent swapping of HCs between HA molecules does not occur. We now describe our results of HC transfer experiments to chondroitin sulfate A, chemically desulfated chondroitin, chemoenzymatically synthesized chondroitin, unsulfated heparosan, heparan sulfate, and alginate. Of these potential HC acceptors, only chemically desulfated chondroitin and chemoenzymatically synthesized chondroitin were HC acceptors. The kinetics of HC transfer to chondroitin was similar to HA. At earlier time points, HCs were more widely distributed among the different sizes of chondroitin chains. As time progressed, the HCs migrated to lower molecular weight chains of chondroitin. Our interpretation is that TSG-6 swaps the HCs from the larger, reversible sites on chondroitin chains, which function as HC acceptors, onto smaller chondroitin chains, which function as irreversible HC acceptors. HCs transferred to smaller chondroitin chains were unable to be swapped off the smaller chondroitin chains and transferred to HA. HCs transferred to high molecular weight HA were unable to be swapped onto chondroitin. We also present data that although chondroitin was a HC acceptor, HA was the preferred acceptor when chondroitin and HA were in the same reaction mixture. PMID:25135638

HCS-Neurons: identifying phenotypic changes in multi-neuron images upon drug treatments of high-content screening.

PubMed

Charoenkwan, Phasit; Hwang, Eric; Cutler, Robert W; Lee, Hua-Chin; Ko, Li-Wei; Huang, Hui-Ling; Ho, Shinn-Ying

2013-01-01

High-content screening (HCS) has become a powerful tool for drug discovery. However, the discovery of drugs targeting neurons is still hampered by the inability to accurately identify and quantify the phenotypic changes of multiple neurons in a single image (named multi-neuron image) of a high-content screen. Therefore, it is desirable to develop an automated image analysis method for analyzing multi-neuron images. We propose an automated analysis method with novel descriptors of neuromorphology features for analyzing HCS-based multi-neuron images, called HCS-neurons. To observe multiple phenotypic changes of neurons, we propose two kinds of descriptors which are neuron feature descriptor (NFD) of 13 neuromorphology features, e.g., neurite length, and generic feature descriptors (GFDs), e.g., Haralick texture. HCS-neurons can 1) automatically extract all quantitative phenotype features in both NFD and GFDs, 2) identify statistically significant phenotypic changes upon drug treatments using ANOVA and regression analysis, and 3) generate an accurate classifier to group neurons treated by different drug concentrations using support vector machine and an intelligent feature selection method. To evaluate HCS-neurons, we treated P19 neurons with nocodazole (a microtubule depolymerizing drug which has been shown to impair neurite development) at six concentrations ranging from 0 to 1000 ng/mL. The experimental results show that all the 13 features of NFD have statistically significant difference with respect to changes in various levels of nocodazole drug concentrations (NDC) and the phenotypic changes of neurites were consistent to the known effect of nocodazole in promoting neurite retraction. Three identified features, total neurite length, average neurite length, and average neurite area were able to achieve an independent test accuracy of 90.28% for the six-dosage classification problem. This NFD module and neuron image datasets are provided as a freely downloadable MatLab project at http://iclab.life.nctu.edu.tw/HCS-Neurons. Few automatic methods focus on analyzing multi-neuron images collected from HCS used in drug discovery. We provided an automatic HCS-based method for generating accurate classifiers to classify neurons based on their phenotypic changes upon drug treatments. The proposed HCS-neurons method is helpful in identifying and classifying chemical or biological molecules that alter the morphology of a group of neurons in HCS.

Review and evaluation of methods for analyzing capacity at signalized intersections.

DOT National Transportation Integrated Search

1996-01-01

VDOT's current policy is to use and accept from others the 1994 Highway Capacity Manual (HCM) as the basis for capacity analysis on Virginia's streets and highways. VDOT uses the latest version of the Highway Capacity Software (HCS). Software program...

Period Prevalence and Perceived Side Effects of Hormonal Contraceptive Use and the Menstrual Cycle in Elite Athletes.

PubMed

Martin, Daniel; Sale, Craig; Cooper, Simon B; Elliott-Sale, Kirsty J

2017-12-28

To identify the period prevalence of hormonal contraceptive (HC) use and characterise the perceived side effects associated with the menstrual cycle and HC use. 430 elite female athletes completed a questionnaire to assess; the period prevalence of HC use, the reasons for initiation and discontinuation of HCs and the side effects experienced by HC and non-HC users. Descriptive statistics, between-group comparisons and associations between categorical variables were calculated. 49.5% of athletes were currently using HCs and 69.8% had used HCs at some point. Combined oral contraceptives were most commonly used (68.1%), with 30.0% using progestin-only contraceptives (implant = 13.1%; injection = 3.7%; intrauterine system = 2.8%). Perceived negative side effects were more common with progestin-only HC use (39.1%) compared to combined HC use (17.8%; P = 0.001) and were most prevalent in implant users (53.6%; P = 0.004). HC users reported perceived positive side effects relating to the ability to predict and/or manipulate the timing, frequency and amount of menstrual bleeding. Non-HC users had a menstrual cycle length of 29 ± 5 d and 77.4% reported negative side effects during their menstrual cycle, primarily during days 1-2 of menstruation (81.6%). Approximately half of elite athletes used HCs and progestin-only contraceptive users reported greater incidences of negative side effects, especially with the implant. Due to the high inter-individual variability in reported side effects, athletes and practitioners should maintain an open dialogue to pursue the best interests of the athlete.

Frequencies of neuronal autoantibodies in healthy controls

PubMed Central

Lang, Katharina

2017-01-01

Objective: To provide an extensive overview on the prevalence of antibodies against neuronal surfaces (neuronal surface antibody [NSAb]) in healthy participants and disease controls. Methods: We searched the PubMed database (1974 to October 2016) for studies that analyzed frequencies of 22 different NSAbs in serum or CSF and included controls. Antibody prevalence was calculated for patients with NSAb-mediated disease and controls, including healthy participants, and those with neurologic and nonneurologic diseases. Different assays for antibody detection were compared. Results: In 309 articles, 743,299 antibody tests for 22 NSAbs were performed, including 30,485 tests for 19 NSAbs in healthy controls (HCs). Of these, 26,423 (86.7%) were tested with current standard methods, usually cell-based assays. Prevalence was very low in HCs (mean 0.23%, absent for 9/19 antibodies), and test numbers ranged from 21 to 3,065 per antibody. One study reported >1,000 healthy participants, and the others contained 21–274 samples. CSF samples were virtually not available from HCs. NSAb prevalence was considerably higher (1.5%) in 69,850 disease controls, i.e., patients not initially suspected to have NSAb-mediated diseases. Antibody determination in controls using nonstandard assays (such as ELISA) resulted in 6% positivity. Conclusions: NSAbs are rarely found in healthy participants, particularly with standard detection methods, suggesting high disease specificity and supporting their diagnostic usefulness. Conversely, positive titers in atypical patients might point to the still expanding phenotypic spectrum. Future studies should include more CSF samples, data from HCs, and experimental evidence for antibody pathogenicity. PMID:28761905

Wild-type cells rescue genotypically Math1-null hair cells in the inner ears of chimeric mice.

PubMed

Du, Xiaoping; Jensen, Patricia; Goldowitz, Daniel; Hamre, Kristin M

2007-05-15

The transcription factor Math1 has been shown to be critical in the formation of hair cells (HCs) in the inner ear. However, the influence of environmental factors in HC specification suggests that cell extrinsic factors are also crucial to their development. To test whether extrinsic factors impact development of Math1-null (Math1(beta-Gal/beta-Gal)) HCs, we examined neonatal (postnatal ages P0-P4.5) Math1-null chimeric mice in which genotypically mutant and wild-type cells intermingle to form the inner ear. We provide the first direct evidence that Math1-null HCs are able to be generated and survive in the conducive chimeric environment. beta-Galactosidase expression was used to identify genetically mutant cells while cells were phenotypically defined as HCs by morphological characteristics notably the expression of HC-specific markers. Genotypically mutant HCs were found in all sensory epithelia of the inner ear at all ages examined. Comparable results were obtained irrespective of the wild-type component of the chimeric mice. Thus, genotypically mutant cells retain the competence to differentiate into HCs. The implication is that the lack of the Math1 gene in HC precursors can be overcome by environmental influences, such as cell-cell interactions with wild-type cells, to ultimately result in the formation of HCs.

Photospheric and coronal magnetic fields in 1974 - 2015: A comparison of six magnetographs

NASA Astrophysics Data System (ADS)

Virtanen, I. I.; Mursula, K.

2015-12-01

Photospheric magnetic field has been measured since 1950s and digital synoptic data exists since 1970s. We study the long-term development of photospheric and coronal magnetic fields, using Wilcox Solar Observatory (WSO), Mount Wilson, Kitt Peak, Solis, SOHO/MDI and SDO/HMI measurements of the photospheric magnetic field and the the potential field source surface (PFSS) model. We pay particular attention to the occurrence of the hemispheric asymmetry of the coronal field. The solar and heliospheric magnetic fields are systematically north-south asymmetric. The southward shift of the heliospheric current sheet (HCS) (the so-called Bashful ballerina phenomenon) is a persistent pattern, which occurs typically for about three years during the late declining phase of solar cycle. Multipole analysis of the photospheric magnetic field has shown that the Bashful ballerina is mainly due to the g02 quadrupole term, which is oppositely signed to the dipole moment and reflects the larger magnitude of the southern polar field. The six data sets are in general in a good agreement with each other, but the different spatial resolution causes difference some in results. Moreover, there are number of deviations in different individual data sets that are not related to resolution, e.g., in WSO data and in the current version of Kitt Peak 512 channel magnetograph data. We note that the two lowest harmonic coefficients do not scale with the overall magnitude of photospheric synoptic magnetic maps. Scaling factors based on histogram techniques can be as large as 10 (from Wilcox to HMI), but the corresponding factor in dipole strength is typically less than two. Scaling also depends on the harmonic coefficient. This should be noted, e.g., when using synoptic maps as input for coronal models. We find that, despite the differences between the six different data sets, especially in the measurements at the highest latitudes, they all support the southward shift of the HCS. At the moment, polar fields have reversed and are strengthening especially in the southern hemisphere, leading to the bashful ballerina, but it is not necessary the final condition during the solar minimum after solar cycle 24. Accordingly, it seems that the Ballerina will be bashful even during cycle 24, although final conclusions must wait the later declining phase.

Atypical energetic particle events observed prior energetic particle enhancements associated with corotating interaction regions

NASA Astrophysics Data System (ADS)

Khabarova, Olga; Malandraki, Olga; Zank, Gary; Jackson, Bernard; Bisi, Mario; Desai, Mihir; Li, Gang; le Roux, Jakobus; Yu, Hsiu-Shan

2017-04-01

Recent studies of mechanisms of particle acceleration in the heliosphere have revealed the importance of the comprehensive analysis of stream-stream interactions as well as the heliospheric current sheet (HCS) - stream interactions that often occur in the solar wind, producing huge magnetic cavities bounded by strong current sheets. Such cavities are usually filled with small-scale magnetic islands that trap and re-accelerate energetic particles (Zank et al. ApJ, 2014, 2015; le Roux et al. ApJ, 2015, 2016; Khabarova et al. ApJ, 2015, 2016). Crossings of these regions are associated with unusual variations in the energetic particle flux up to several MeV/nuc near the Earth's orbit. These energetic particle flux enhancements called "atypical energetic particle events" (AEPEs) are not associated with standard mechanisms of particle acceleration. The analysis of multi-spacecraft measurements of energetic particle flux, plasma and the interplanetary magnetic field shows that AEPEs have a local origin as they are observed by different spacecraft with a time delay corresponding to the solar wind propagation from one spacecraft to another, which is a signature of local particle acceleration in the region embedded in expanding and rotating background solar wind. AEPEs are often observed before the arrival of corotating interaction regions (CIRs) or stream interaction regions (SIRs) to the Earth's orbit. When fast solar wind streams catch up with slow solar wind, SIRs of compressed heated plasma or more regular CIRs are created at the leading edge of the high-speed stream. Since coronal holes are often long-lived structures, the same CIR re-appears often for several consecutive solar rotations. At low heliographic latitudes, such CIRs are typically bounded by forward and reverse waves on their leading and trailing edges, respectively, that steepen into shocks at heliocentric distances beyond 1 AU. Energetic ion increases have been frequently observed in association with CIR's shocks, and these shocks to be believed to accelerate ions up to several MeV per nucleon. In this paradigm particle acceleration is commonly believed to occur mainly at the well-formed reverse shock at 2-3 AU with particles streaming back from the shocks from the outer heliosphere to 1 AU (Malandraki et al., 2007). However, AEPEs observed for many hours before the crossing of the forward shock (or even before the leading edge of a CIR without well-formed forward shock) cannot be explained within the framework of this paradigm. We have recently found that the effect of pre-CIR AEPEs occurs mainly as a result of the formation of a region filled with magnetic islands compressed between the high-density leading edge of a CIR and the HCS (Khabarova et al. ApJ, 2016). We show here that any kind of complicated stream-CIR interactions may lead to the same effect due to the formation of magnetic cavities in front of CIRs. The analysis of in situ multi-spacecraft measurements often suggests very complicated ways of propagation of streams and current sheets that form magnetic cavities. In the case of multiple stream-stream interaction, comparisons of data from distant spacecraft may be puzzling and even useless for understanding the large-scale topology of the region of particle acceleration, because even several point measurements cannot reconstruct approximate forms of the magnetic cavities and shed light on the pre-history of their origin and evolution. We employ interplanetary scintillation tomographic data for reconstructions of the solar wind speed, density and interplanetary magnetic field profiles to understand a 3-D picture of stream interactions responsible for pre-CIR AEPEs. This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 637324

Deletion of Brg1 causes abnormal hair cell planer polarity, hair cell anchorage, and scar formation in mouse cochlea.

PubMed

Jin, Yecheng; Ren, Naixia; Li, Shiwei; Fu, Xiaolong; Sun, Xiaoyang; Men, Yuqin; Xu, Zhigang; Zhang, Jian; Xie, Yue; Xia, Ming; Gao, Jiangang

2016-06-03

Hair cells (HCs) are mechanosensors that play crucial roles in perceiving sound, acceleration, and fluid motion. The precise architecture of the auditory epithelium and its repair after HC loss is indispensable to the function of organ of Corti (OC). In this study, we showed that Brg1 was highly expressed in auditory HCs. Specific deletion of Brg1 in postnatal HCs resulted in rapid HC degeneration and profound deafness in mice. Further experiments showed that cell-intrinsic polarity of HCs was abolished, docking of outer hair cells (OHCs) by Deiter's cells (DCs) failed, and scar formation in the reticular lamina was deficient. We demonstrated that Brg1 ablation disrupted the Gαi/Insc/LGN and aPKC asymmetric distributions, without overt effects on the core planer cell polarity (PCP) pathway. We also demonstrated that Brg1-deficient HCs underwent apoptosis, and that leakage in the reticular lamina caused by deficient scar formation shifted the mode of OHC death from apoptosis to necrosis. Together, these data demonstrated a requirement for Brg1 activity in HC development and suggested a role for Brg1 in the proper cellular structure formation of HCs.

Coronal and heliospheric magnetic flux circulation and its relation to open solar flux evolution

NASA Astrophysics Data System (ADS)

Lockwood, Mike; Owens, Mathew J.; Imber, Suzanne M.; James, Matthew K.; Bunce, Emma J.; Yeoman, Timothy K.

2017-06-01

Solar cycle 24 is notable for three features that can be found in previous cycles but which have been unusually prominent: (1) sunspot activity was considerably greater in the northern/southern hemisphere during the rising/declining phase; (2) accumulation of open solar flux (OSF) during the rising phase was modest, but rapid in the early declining phase; (3) the heliospheric current sheet (HCS) tilt showed large fluctuations. We show that these features had a major influence on the progression of the cycle. All flux emergence causes a rise then a fall in OSF, but only OSF with foot points in opposing hemispheres progresses the solar cycle via the evolution of the polar fields. Emergence in one hemisphere, or symmetric emergence without some form of foot point exchange across the heliographic equator, causes poleward migrating fields of both polarities in one or both (respectively) hemispheres which temporarily enhance OSF but do not advance the polar field cycle. The heliospheric field observed near Mercury and Earth reflects the asymmetries in emergence. Using magnetograms, we find evidence that the poleward magnetic flux transport (of both polarities) is modulated by the HCS tilt, revealing an effect on OSF loss rate. The declining phase rise in OSF was caused by strong emergence in the southern hemisphere with an anomalously low HCS tilt. This implies the recent fall in the southern polar field will be sustained and that the peak OSF has limited implications for the polar field at the next sunspot minimum and hence for the amplitude of cycle 25.