999 resultados para OFF alpha


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The correlation between cholinergic sensitivity and the level of stratification for ganglion cells was examined in the rabbit retina. As examples, we have used ON or OFF alpha ganglion cells and ON/OFF directionally selective (DS) ganglion cells. Nicotine, a cholinergic agonist, depolarized ON/OFF DS ganglion cells and greatly enhanced their firing rates but it had modest excitatory effects on ON or OFF alpha ganglion cells. As previously reported, we conclude that DS ganglion cells are the most sensitive to cholinergic drugs. Confocal imaging showed that ON/OFF DS ganglion cells ramify precisely at the level of the cholinergic amacrine cell dendrites, and co-fasciculate with the cholinergic matrix of starburst amacrine cells. However, neither ON or OFF alpha ganglion cells have more than a chance association with the cholinergic matrix. Z -axis reconstruction showed that OFF alpha ganglion cells stratify just below the cholinergic band in sublamina a while ON alpha ganglion cells stratify just below cholinergic b . The latter is at the same level as the terminals of calbindin bipolar cells. Thus, the calbindin bipolar cell appears to be a prime candidate to provide the bipolar cell input to ON alpha ganglion cells in the rabbit retina. We conclude that the precise level of stratification is correlated with the strength of cholinergic input. Alpha ganglion cells receive a weak cholinergic input and they are narrowly stratified just below the cholinergic bands.

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In the mammalian retina, AII amacrine cells are essential in the rod pathway for dark-adapted vision. But they also have a “day job”, to provide inhibitory inputs to certain OFF ganglion cells in photopic conditions. This is known as crossover inhibition. Physiological evidence from several different labs implies that AII amacrine cells provide direct input to certain OFF ganglion cells. However, previous EM analysis of the rabbit retina suggests that the dominant output of the AII amacrine cell in sublamina a goes to OFF cone bipolar cells (Strettoi et al., 1992). Two OFF ganglion cell types in the rabbit retina, OFF α and G9, were identified by a combination of morphological criteria such as dendritic field size, dye coupling, mosaic properties and stratification depth. The AII amacrine cells (AIIs) were labeled with an antibody against calretinin and glycine receptors were marked with an antibody against the α1 subunit. This material was analyzed by triple-label confocal microscopy. We found the lobules of AIIs made close contacts at many points along the dendrites of individual OFF α and G9 ganglion cells. At these potential synaptic sites, we also found punctate labeling for the glycine receptor α1 subunit. The presence of a post-synaptic marker such as the α1 glycine receptor at contact points between AII lobules and OFF ganglion cells supports a direct inhibitory input from AIIs. This pathway provides for crossover inhibition in the rabbit retina whereby light onset provides an inhibitory signal to OFF α and G9 ganglion cells. Thus, these two OFF ganglion cell types receive a mixed excitatory and inhibitory drive in response to light stimulation.

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The BLM-OCS (Bureau of Land Management-Outer Continental Shelf) program was designed to establish chemical, biological, and geological baseline on the South Texas Continental Shelf. The focus for the geological program was to establish the nature and amount of the suspended sediment in the water column, of the Holocene sediments on the shelf, and to identify and locate regions of geology conditions which may be hazardous to OCS operations. To accomplish these goals three cruises were planned. The report constitutes results of the first cruise. The results of these cruises associated with the subsequent laboratory analysis, enabled to establish a detailed baseline in order to provide significant geologic and biologic data for environmental assessment. Dredges recovered are available at University of Texas (see: BLM/OCS South Texas Outer Continental Shelf (STOCS) Project Sediment Data http://www.ngdc.noaa.gov/docucomp/page?xml=NOAA/NESDIS/NGDC/MGG/Geology/iso/xml/G02888.xml&view=getDataView&header=none).

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Aims. To detect line effects using spectropolarimetry in order to find evidence of rotating disks and their respective symmetry axes in T Tauri stars. Methods. We used the IAGPOL imaging polarimeter along with the Eucalyptus-IFU to obtain spectropolarimetric measurements of the T Tauri stars RY Tau (two epochs) and PX Vul (one epoch). Evidence of line effects showing a loop in the Q-U diagram favors a compact rather than an extended source for the line photons in a rotating disk. In addition, the polarization position angle (PA) obtained using the line effect can constrain the symmetry axis of the disk. Results. RY Tau shows a variable H alpha double peak in 2004-2005 data. A polarization line effect is evident in the Q-U diagram for both epochs confirming a clockwise rotating disk. A single loop is evident in 2004 changing to a linear excursion plus a loop in 2005. Interestingly, the intrinsic PA calculated using the line effect is consistent between our two epochs (similar to 167 degrees). An alternative intrinsic PA computed from the interstellar polarization-corrected continuum and averaged between 2001-2005 yielded a PA similar to 137 degrees. This last value is closer to perpendicular to the observed disk direction (similar to 25 degrees), as expected from single scattering in an optically thin disk. For PX Vul, we detected spectral variability in H alpha along with non-variable continuum polarization when compared with previous data. The Q-U diagram shows a well-defined loop in H alpha associated with a counter-clockwise rotating disk. The symmetry axis inferred from the line effect has a PA similar to 91 degrees (with an ambiguity of 90 degrees). Our results confirm previous evidence that the emission line in T Tauri stars has its origin in a compact source scattered off a rotating accretion disk.

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Abstract:INTRODUCTION:Despite the recommendations by interpretation of resistance ratios obtained in laboratory bioassays, little is known about the actual impact of these results in the effectiveness of vector control activities in the field. In this context, our objective was to determine the mean value of different resistance ratios obtained by laboratory bioassays performed as part of the chemical control strategies of Triatoma sordida in the field.METHODS:Field bioassays were developed in Monte Azul and Coração de Jesus (Southeast, Brazil). In each location, samples were formed with three domestic units treated with alpha-cypermethrin 20.0% (Alfatek (r) 200 SC). One day after spraying, 10 fifth-instar nymphs remained in contact with the surfaces treated (adobe with plaster, adobe without plaster, or wood) with insecticide in plastic cones for 72h. Three cones were exposed inside the intradomicile and the peridomicile. The insects in the control group were exposed to an insecticide-free piece of cardboard. Mortality was measured 72h after removal of the insects from the treated surfaces. The tests were realized in triplicate.RESULTS:Mortality was 100.0% in all locations, except for Monte Azul; Landinho (96.6%) and Coração de Jesus; Barriguda (96.6%).CONCLUSIONS:Although the resistant populations in laboratory tests proved to be susceptible in the field, this observation is not sufficient to suggest that the cut-off points used to justify the resistance ratio should be changed. In this sense, we recommend that laboratory and field bioassays are carried out with a greater number of Triatominae populations to allow more in-depth consideration of the subject.

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The changes in nutritional parameters and adipocytokines after structured intermittent interruption of highly active antiretroviral treatment of patients with chronic HIV infection are analyzed. Twenty-seven patients with chronic HIV infection (median CD4+ T cell count/microl: nadir, 394; at the beginning of structured interruptions, 1041; HIV viral load: nadir, 41,521 copies/ml; at the beginning of structured interruptions <50 copies/ml; median time of previous treatment: 60 months) were evaluated during three cycles of intermittent interruptions of therapy (8 weeks on/4 weeks off). CD4+ T cell count, HIV viral load, anthropometric measures, and serum concentrations of triglycerides, cholesterol, leptin, and tumor necrosis factor and its soluble receptors I and II were determined. After the three cycles of intermittent interruptions of therapy, no significant differences in CD4+ T cell count/microl, viral load, or serum concentrations of cholesterol or triglycerides with reference to baseline values were found. A near-significant higher fatty mass (skinfold thicknesses, at the end, 121 mm, at the beginning, 100 mm, p = 0.100), combined with a significant increase of concentration of leptin (1.5 vs. 4.7 ng/ml, p = 0,044), as well as a decrease in serum concentrations of soluble receptors of tumor necrosis factor (TNFRI, 104 vs. 73 pg/ml, p = 0.022; TNFRII 253 vs. 195 pg/ml, p = 0.098) were detected. Structured intermittent interruption of highly active antiretroviral treatment of patients with chronic HIV infection induces a valuable positive modification in markers of lipid turnover and adipose tissue mass.

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The Alpha-Tocopherol Beta-Carotene Cancer Prevention Study has provided the first evidence implicating vitamin E in hormone synthesis. The effect of vitamin E on stereoidogenesis in testes and adrenal glands was assessed in growing rats using Affymetrix gene-chip technology. Dietary supplementation of rats with vitamin E (60 mg/kg feed) for a period of 429 days caused a significant repression of genes encoding for proteins centrally involved in the uptake (low-density lipoprotein receptor) and de novo synthesis (for example, 7-dehydrocholesterol reductase, 3-hydroxy-3-methylglutaryl coenzyme A synthase, 3-hydroxy-3-methylglutaryl-coenzyme A reductase, isopentenyl-diphosphate delta-isomerase, and farnesyl pyrophosphate synthetase) of cholesterol, the precursor of all steroid hormones. The present investigation indicates that dietary vitamin E may induce changes in stereoidogenesis by affecting cholesterol homeostasis.

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We study the two-alpha-particle (alpha alpha) system in an Effective Field Theory (EFT) for halo-like systems. We propose a power Counting that incorporates the subtle interplay of strong and electromagnetic forces leading to a narrow resonance at an energy of about 0.1 MeV. We investigate the EFT expansion in detail, and compare its results with existing low-energy aa phase shifts and previously determined effective-range parameters. Good description of the data is obtained with a surprising amount of fine-tuning. This scenario can be viewed as an expansion around the limit where, when electromagnetic interactions are turned off, the (8)Be ground state is at threshold and exhibits conformal invariance. We also discuss possible extensions to systems with more than two alpha particles. (c) 2008 Elsevier B.V. All rights reserved.

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Supercritical fluid extraction with CO2, Performed in a home-made system, of rhizomes of Dorstenia bryoniifolia Mart. ex Miq. (Moraceae) and of bark roots of Brosimum gaudichaudii Trecul (Moraceae) afforded crude extracts that were analysed by high resolution gas chromatography (HRGC). The D. bryoniifolia extract contained, besides the previously reported pimpinelin and isobergapten, the furocoumarins psoralen, bergapten, isopimpinelin and the triterpenes alpha- and beta-amyrin and the acetate of the latter. The B. gaudichaudii extract contained a number of terpenoids as well as the previously reported psoralen and bergapten. Supercritical fluid extraction gave extracts qualitatively similar to those obtained by Soxhlet extraction with hexane and, together with off-line HRGC, was shown to be a fast and accurate technique to be used in rapid phytochemical examination.

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Aus dem tumorreaktiven T-Zellrepertoire der Melanompatientin Ma-Mel-86/INTH, bei der im Verlauf Lymphknotenmetastasen HLA-Klasse I-negativer Tumorzellen auftraten, wurden durch Stimulation mit autologen Tumorzellen CD8+ T-Zellklone isoliert und expandiert, die auf Melanomzellen der Patientin CSF2RA (engl. GM-CSF receptor alpha chain) in HLA-unabhängiger Weise erkannten. Aus einem der T-Zellklone wurde ein CSF2RA-reaktiver α:β-T-Zellrezeptor (TCR, engl. T-cell receptor) kloniert (Bezeichnung: TCR-1A.3/46). Die α-Kette des TCR enthielt die Domänen TRAV14/DV4*01, TRAJ48*01 und TRAC*01, die β-Kette die Domänen TRBV10-3*01, TRBD2*01, TRBJ2-7*01 und TRBC2*01. Durch Austausch der humanen konstanten gegen die homologen murinen Domänen wurde der TCR optimiert (Bezeichnung: cTCR-1A.3/46) und hinsichtlich seiner Expression und Funktionalität nach retroviralem Transfer in humane PBMC (engl. peripheral blood mononuclear cells) im 51Chromfreisetzungstest, im IFN-γ-ELISpot-Assay und in einem Degranulations-Assay validiert. TCR-transgene T-Zellen lysierten nicht nur spezifisch die HLA-defizienten, CSF2RA+ Melanomlinien des Modells Ma-Mel-86, sondern erkannten auch Zelllinien verschiedener Spezies nach Transfektion von CSF2RA sowie Monozyten, Granulozyten, dendritische Zellen und ein breites Spektrum hämatologischer Malignome myeloiden Ursprungs ungeachtet deren HLA-Phänotypen. Lymphatische Zellen sowie CD34+ Blutstammzellen wurden in In vitro-Untersuchungen nicht erkannt. Der Zusatz von GM-CSF zu Zellen, die CSF2RA und CSF2RB exprimierten, inhibierte die Erkennung durch TCR-transgene PBMC, während die Koexpression der α- und der ß-Kette des GM-CSF-Rezeptors alleine keinen negativen Effekt auf die Erkennung hatte. Daraus war zu schließen, dass CSF2RA präferentiell freistehend und weniger nach Integration in den heteromultimerischen GM-CSF-Rezeptor-Komplex erkannt wurde. In der zweidimensionalen Collier-de-Perles-Visualisierung der IMGT-Datenbank (engl. International immunogenetics information system) wies der CSF2RA-reaktive TCR-1A.3/46 im Vergleich zu TCR von konventionellen, HLA-restringierten T-Zellen keine Besonderheiten auf. Darüber hinaus waren auch die von den HLA-unabhängigen T-Zellen exprimierten CD8-Moleküle identisch zu den CD8-Molekülen HLA-abhängiger CTL (engl. cytotoxic T lymphocytes). Die Präsenz von CD8-Molekülen förderte die HLA-unabhängige Erkennung von CSF2RA, schien aber dafür nicht zwingend erforderlich zu sein, da Antikörper gegen CD8 die Erkennung zu ca. 65 % blockierten und TCR-transgene CD4+ T-Zellen im Vergleich zu TCR-transduzierten CD8+ T-Zellen eine deutlich verringerte, aber noch erhaltene Funktionalität aufwiesen. Es ist derzeit nicht klar, ob HLA-unabhängige T-Zellen gegen CSF2RA im peripheren Blut der Patientin vorkamen, weil sie der im Tiermodell postulierten Thymusselektion MHC-unabhängiger TCR (Tikhonova et al., Immunity 36:79, 2012) entkommen waren, oder weil ein ursprünglich gegen einen HLA-Peptid-Komplex gerichteter TCR eine HLA-unabhängige Kreuzreaktivität aufwies. CSF2RA verbessert die Glucoseutilisation in malignen Zellen, und es wurden ihm embryotrophe Eigenschaften zugeschrieben (Spielholz et al., Blood 85:973, 1995; Sjöblom et al., Biol. Reprod. 67:1817, 2002). Damit kann CSF2RA malignes Wachstum fördern und ist somit ein potentielles Zielmolekül für die Immuntherapie. Seine HLA-unabhängige Erkennung würde sowohl die HLA-Vielfalt als auch den HLA-Verlust als typische Limitationen der T-Zellimmuntherapie umgehen. Zur Überprüfung der In vivo-Spezifität des HLA-unabhängigen TCR gegen CSF2RA und damit zum Ausschluss relevanter off-tumor-/on-target- bzw. off-tumor-/off-target-Effekte ist jedoch eine Testung in einem präklinischen Tiermodell erforderlich.

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Cathepsin D (Cath-D) expression in human primary breast cancer has been associated with a poor prognosis. In search of a better understanding of the Cath-D substrates possibly involved in cancer invasiveness and metastasis, we investigated the potential interactions between this protease and chemokines. Here we report that purified Cath-D, as well as culture supernatants from the human breast carcinoma cell lines MCF-7 and T47D, selectively degrade macrophage inflammatory protein (MIP)-1 alpha (CCL3), MIP-1 beta (CCL4), and SLC (CCL21). Proteolysis was totally blocked by the protease inhibitor pepstatin A, and specificity of Cath-D cleavage was demonstrated using a large chemokine panel. Whereas MIP-1 alpha and MIP-1 beta degradation was rapid and complete, cleavage of SLC was slow and not complete. Mass spectrometry analysis showed that Cath-D cleaves the Leu(58) to Trp(59) bond of SLC producing two functionally inactive fragments. Analysis of Cath-D proteolysis of a series of monocyte chemoattractant protein-3/MIP-1 beta hybrids indicated that processing of MIP-1 beta might start by cleaving off amino acids located in the C-terminal domain. In situ hybridization studies revealed MIP-1 alpha, MIP-1 beta, and Cath-D gene expression mainly in the stromal compartment of breast cancers whereas SLC transcripts were found in endothelial cells of capillaries and venules within the neoplastic tissues. Cath-D production in the breast carcinoma cell lines MCF-7 and T47D, as assessed by enzyme-linked immunosorbent assay of culture supernatants and cell lysates, was not affected by stimulation with chemokines such as interleukin-8 (CXCL8), SDF-1 (CXCL12), and SLC. These data suggest that inactivation of chemokines by Cath-D possibly influences regulatory mechanisms in the tumoral extracellular microenvironment that in turn may affect the generation of the antitumoral immune response, the migration of cancer cells, or both processes.

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Uranium (U) concentrations and activity ratios (d234U) of authigenic carbonates are sensitive recorders of different fluid compositions at submarine seeps of hydrocarbon-rich fluids ("cold seeps") at Hydrate Ridge, off the coast of Oregon, USA. The low U concentrations (mean: 1.3 ± 0.4 µg/g) and high 234U values (165-317 per mil) of gas hydrate carbonates reflect the influence of sedimentary pore water indicating that these carbonates were formed under reducing conditions below or at the seafloor. Their 230Th/234U ages span a time interval from 0.8 to 6.4 ka and cluster around 1.2 and 4.7 ka. In contrast, chemoherm carbonates precipitate from marine bottom water marked by relatively high U concentrations (mean: 5.2 ± 0.8 µg/g) and a mean d234U ratio of 166 ± 3 per mil. Their U isotopes reflect the d234U ratios of the bottom water being enriched in 234U relative to normal seawater. Simple mass balance calculations based on U concentrations and their corresponding d234U ratios reveal a contribution of about 11% of sedimentary pore water to the bottom water. From the U pore water flux and the reconstructed U pore water concentration a mean flow rate of about 147 ± 68 cm/a can be estimated. 230Th/234U ages of chemoherm carbonates range from 7.3 to 267.6 ka. 230Th/234U ages of two chemoherms (Alvin and SE-Knoll chemoherm) correspond to time intervals of low sealevel stands in marine isotope stages (MIS) 2, 4, 5, 6, 7 and 8. This observation indicates that fluid flow at cold seep sites sensitively reflects pressure changes of the hydraulic head in the sediments. The d18OPDB ratios of the chemoherm carbonates support the hypothesis of precipitation during glacial times. Deviations of the chemoherm d18O values from the marine d18O record can be interpreted as to reflect temporally and spatially varying bottom water and/or vent fluid temperatures during carbonate precipitation between 2.6 and 8.6°C.

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Biogenic opal and organic carbon vertical rain rates in sediment cores reveal a strong cyclicity in the productivity of the upwelling system off presently arid northern Chile during the last 100,000 years. Changes in productivity are found to be in phase with the precessional cycle (~20,000 years) and with inputs of iron from the continent. During austral summer insolation maxima, increased precipitation and river runoff in the region appear to have brought high inputs of iron, mainly from the Andes, to the coastal ocean enhancing primary productivity there. We interpret our results as providing evidence for iron control of past productivity in this upwelling system and for a tight link between productivity and orbital forcing at midlatitudes.

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This report contains the occurrence data for dinoflagellate cysts recorded from 163 samples taken from Sites 902 through 906, during Ocean Drilling Program (ODP) Leg 150. The dinoflagellate cyst (dinocyst) stratigraphy has been presented in Mountain, Miller, Blum, et al. (1994, doi:10.2973/odp.proc.ir.150.1994), and was based on these data. This report provides the full dinocyst data set supporting the dinocyst stratigraphic interpretations made in Mountain, Miller, Blum, et al. (1994). For Miocene shipboard dinocyst stratigraphy, I delineated 10 informal zones: pre-A, and A through I, in ascending stratigraphic order. These zones are defined in Shipboard Scientific Party (1994a, doi:10.2973/odp.proc.ir.150.103.1994), and are based on my studies of Miocene dinocyst stratigraphy in the Maryland and Virginia coastal plain (de Verteuil and Norris, 1991, 1992; de Verteuil, 1995). This zonation has been slightly revised (de Verteuil and Norris, 1996), and the new formal zone definitions are repeated below. Each new zone has an alpha-numeric abbreviation starting with "DN" (for Dinoflagellate Neogene). The equivalence between the informal zones reported in Mountain, Miller, Blum, et al. (1994), and the new DN zones is illustrated in Figure 1. For clarity, I delineated both zonations in the range charts that accompany this report (Tables 1-6). De Verteuil and Norris (1996a), using these and other data, correlated the DN zonation with the geological time scale of Berggren et al. (1995). Figure 2 summarizes these correlations and can be used to check the chronostratigraphic position of samples in this report, as determined by dinocyst stratigraphy. A thorough discussion of the basis for, and levels of uncertainty associated with, these correlations to the Cenozoic time scale can be found in de Verteuil and Norris (1996a). The Appendix lists all the dinocyst taxa recorded during shipboard analyses of Leg 150 samples. Open nomenclature is used for undescribed taxa. The range charts and Appendix also include reference to several new taxa that de Verteuil and Norris (1996b) described from Miocene coastal plain strata in Maryland and Virginia. Names of these taxa in Tables 1 through 6 and in the Appendix of this report are not intended for effective publication as defined in the International Code of Botanical Nomenclature (ICBN, Greuter et al., 1994). Therefore, taxonomic nomenclature contained in this report is not to be treated as meeting the conditions of effective and valid publication (ICBN; Article 29).

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Pore water and solid phase from surface sediments of the continental slope off Uruguay and from the Argentine Basin (southwestern Atlantic) were investigated geochemically to ascribe characteristic early diagenetic reactions of iron and manganese. Solid-phase iron speciation was determined by extractions as well as by Mössbauer spectroscopy. Both methods showed good agreement (<6% deviation) for total-Fe speciation. The proportion of easy reducible iron oxyhydroxide relative to total-Fe oxides decreased from the continental slope to the deep sea which is attributed to an increase in crystallinity during transport as well as to a general decrease of iron mobilization. The product of iron reoxidation is Fe oxyhydroxide which made up less than 5% of total Fe. In addition to this fraction, a proportion of smectite bound iron was found to be redox reactive. This fraction made up to 10% of total Fe in sediments of the Argentine Basin and was quantitatively extracted by 1 N HCl. The redox reactive Fe(+II) fraction of smectite was almost completely reoxidized within 24 h under air atmosphere and may therefore considerably contribute to iron redox cycling if bioturbation occurs. In the case of the slope sediments we found concurrent iron and manganese release to pore water. It is not clear whether this is caused by dissimilatory iron and manganese reduction at the same depth or dissimilatory iron reduction alone inducing Mn(+IV) reduction by (abiotic) reaction with released Fe2+. The Argentine Basin sediment showed a significant manganese solid-phase enrichment above the denitrification depth despite the absence of a distinct pore-water gradient of Mn. This implies a recent termination of manganese mobilization and thus a non-steady-state situation with respect to sedimentation or to organic carbon burial rate.