bluuebunny/crossref_metadata_2025 huggingface dataset:
Lack of correlation between the levels of soluble cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and the CT-60 genotypes
Authors: Purohit Sharad , Podolsky Robert , Collins Christin , Zheng Weipeng , Schatz Desmond , Muir Andy , Hopkins Diane , Huang Yi-Hua , She Jin-Xiong
Published: November 2005

Background

Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) plays a critical role in downregulation of antigen-activated immune response and polymorphisms at the CTLA-4 gene have been shown to be associated with several autoimmune diseases including type-1 diabetes (T1D). The etiological mutation was mapped to the CT60-A/G single nucleotide polymorphism (SNP) that is believed to control the processing and production of soluble CTLA-4 (sCTLA-4).

Methods

We therefore determined sCTLA-4 protein levels in the sera from 82 T1D patients and 19 autoantibody positive (AbP) subjects and 117 autoantibody negative (AbN) controls using ELISA. The CT-60 SNP was genotyped for these samples by using PCR and restriction enzyme digestion of a 268 bp DNA segment containing the SNP. Genotyping of CT-60 SNP was confirmed by dye terminating sequencing reaction.

Results

Higher levels of sCTLA-4 were observed in T1D (2.24 ng/ml) and AbP (mean = 2.17 ng/ml) subjects compared to AbN controls (mean = 1.69 ng/ml) with the differences between these subjects becoming significant with age (p = 0.02). However, we found no correlation between sCTLA-4 levels and the CTLA-4 CT-60 SNP genotypes.

Conclusion

Consistent with the higher serum sCTLA-4 levels observed in other autoimmune diseases, our results suggest that sCTLA-4 may be a risk factor for T1D. However, our results do not support the conclusion that the CT-60 SNP controls the expression of sCTLA-4.
The microglial "activation" continuum: from innate to adaptive responses
Authors: Town Terrence , Nikolic Veljko , Tan Jun
Published: November 2005

Microglia are innate immune cells of myeloid origin that take up residence in the central nervous system (CNS) during embryogenesis. While classically regarded as macrophage-like cells, it is becoming increasingly clear that reactive microglia play more diverse roles in the CNS. Microglial "activation" is often used to refer to a single phenotype; however, in this review we consider that a continuum of microglial activation exists, with phagocytic response (innate activation) at one end and antigen presenting cell function (adaptive activation) at the other. Where activated microglia fall in this spectrum seems to be highly dependent on the type of stimulation provided. We begin by addressing the classical roles of peripheral innate immune cells including macrophages and dendritic cells, which seem to define the edges of this continuum. We then discuss various types of microglial stimulation, including Toll-like receptor engagement by pathogen-associated molecular patterns, microglial challenge with myelin epitopes or Alzheimer's β-amyloid in the presence or absence of CD40L co-stimulation, and Alzheimer disease "immunotherapy". Based on the wide spectrum of stimulus-specific microglial responses, we interpret these cells as immune cells that demonstrate remarkable plasticity following activation. This interpretation has relevance for neurodegenerative/neuroinflammatory diseases where reactive microglia play an etiological role; in particular viral/bacterial encephalitis, multiple sclerosis and Alzheimer disease.
Oocytes prevent cumulus cell apoptosis by maintaining a morphogenic paracrine gradient of bone morphogenetic proteins
Authors: Hussein Tamer S. , Froiland David A. , Amato Fred , Thompson Jeremy G. , Gilchrist Robert B.
Published: November 2005

Paracrine factors secreted by the oocyte regulate a broad range of cumulus cell functions. Characteristically, cumulus cells have a low incidence of apoptosis and we proposed that this is due to oocyte-secreted factors acting in an anti-apoptotic manner. Bovine cumulus-oocyte complexes (COC) were aspirated from abattoir-derived ovaries and oocytectomized (OOX) by microsurgical removal of the oocyte. OOX were treated with doses of either denuded oocytes (DO) or various growth factors for 24 hours (± rFSH; 0.1 IU/ml). Proportions of apoptotic cumulus cells were assessed using TUNEL and laser confocal scanning microscopy followed by image analysis. Quantification of Bcl-2 and Bax proteins in OOX was undertaken by western analysis. Oocyte removal led to a significant increase in cumulus cell apoptosis compared with COC controls (35% versus 9% TUNEL positive, respectively; P<0.001). Levels of OOX apoptosis were significantly reversed (P<0.001) in a dose-dependent manner when co-cultured with oocytes. Furthermore, the anti-apoptotic effect of oocyte-secreted factors followed a gradient from the site of the oocyte(s). Growth differentiation factor 9 (GDF9) had no significant effect on cumulus cell apoptosis. By contrast, cumulus cell apoptosis was significantly (P<0.001) reduced by bone morphogenetic proteins (BMP) 15, 6 or 7. Accordingly, levels of anti-apoptotic Bcl-2 were high in OOX+DO and OOX+BMP15 and low with OOX+GDF9 or OOX alone, whereas the reverse was observed for pro-apoptotic Bax. DO, BMP15 and BMP6 were also able to protect cumulus cells from undergoing apoptosis induced by staurosporine. FSH partially prevented apoptosis in all treatment groups (P<0.001). Follistatin and a BMP6 neutralizing antibody, which antagonized the anti-apoptotic effects of BMP15 and BMP6, respectively, whether alone or combined, blocked ∼50% of the anti-apoptotic actions of oocytes. These results are the first to demonstrate that oocyte-secreted factors, and particularly BMP15 and BMP6, maintain the low incidence of cumulus cell apoptosis by establishing a localized gradient of bone morphogenetic proteins.
MIDAS/GPP34, a nuclear gene product, regulates total mitochondrial mass in response to mitochondrial dysfunction
Authors: Nakashima-Kamimura Naomi , Asoh Sadamitsu , Ishibashi Yoshitomo , Mukai Yuri , Shidara Yujiro , Oda Hideaki , Munakata Kae , Goto Yu-ichi , Ohta Shigeo
Published: November 2005

To investigate the regulatory system in mitochondrial biogenesis involving crosstalk between the mitochondria and nucleus, we found a factor named MIDAS (mitochondrial DNA absence sensitive factor) whose expression was enhanced by the absence of mitochondrial DNA (mtDNA). In patients with mitochondrial diseases, MIDAS expression was increased only in dysfunctional muscle fibers. A majority of MIDAS localized to mitochondria with a small fraction in the Golgi apparatus in HeLa cells. To investigate the function of MIDAS, we stably transfected HeLa cells with an expression vector carrying MIDAS cDNA or siRNA. Cells expressing the MIDAS protein and the siRNA constitutively showed an increase and decrease in the total mass of mitochondria, respectively, accompanying the regulation of a mitochondria-specific phospholipid, cardiolipin. In contrast, amounts of the mitochondrial DNA, RNA and proteins did not depend upon MIDAS. Thus, MIDAS is involved in the regulation of mitochondrial lipids, leading to increases of total mitochondrial mass in response to mitochondrial dysfunction.
Endocytosis of megalin by visceral endoderm cells requires the Dab2 adaptor protein
Authors: Maurer Meghan E. , Cooper Jonathan A.
Published: November 2005

Rapid endocytosis of lipoprotein receptors involves NPxY signals contained in their cytoplasmic tails. Several proteins, including ARH and Dab2, can bind these sequences, but their importance for endocytosis may vary in different cell types. The lipoprotein receptor megalin is expressed in the visceral endoderm (VE), a polarized epithelium that supplies maternal nutrients to the early mammalian embryo. Dab2 is also expressed in the VE, and is required for embryo growth and gastrulation. Here, we show that ARH is absent from the VE, and Dab2 is required for uptake of megalin, its co-receptor cubilin, and a cubilin ligand, transferrin, from the brush border of the VE into intracellular vesicles. By making isoform-specific knock-in mice, we show that the p96 splice form of Dab2, which binds endocytic proteins, can fully rescue endocytosis. The more abundant p67 isoform, which lacks some endocytic protein binding sites, only partly rescues endocytosis. Endocytosis of cubilin is also impaired in VE and in mid-gestation visceral yolk sac when p96 is absent. These studies suggest that Dab2 p96 mediates endocytosis of megalin in the VE. In addition, rescue of embryonic viability correlates with endocytosis, suggesting that endocytosis mediated by Dab2 is important for normal development.
Determination of Cerium in Ferrous Alloys
Authors: Steinberg Ralph H.
Published: November 2005

The method is applicable to the determination of cerium in cast iron, carbon and stainless steel. The cerium is co-precipitated with barium as fluorides in an hydrochloric-perchloric acid solution. The ignited precipitate is analyzed spectrographically using the D.C. arc. The lowest detectable amount is of the order of .003% cerium for stainless and somewhat lower for iron and steel.

Synthetic standards for comparison are made by the addition of a standardized cerium solution to a cerium-free alloy similar to the unknown and then carried through the procedure simultaneously.
Spectrographic Analysis of Potassium in Urine and Feces Using the Copper Electrodes
Authors: Honma M. , O'Connor J. D.
Published: November 2005

A spectrographic method for the determination of various elements in urine and feces has been developed using the copper spark method. This study is concerned with the rapid determination of potassium whose analysis is carried out simultaneously with several elements. Since most of the sensitive lines of the various elements occur in the ultra violet region, the analysis of potassium had to be done in this region. The copper spark method eliminates the troublesome cyanogen spectra in the ultra violet thus enabling the use of the 4047.2 Å line of potassium for analysis.

Reproducibility data are presented and the spectrographic method is compared to the conventional gravimetric perchlorate method. The results indicate fairly close correlation.

The solution method has been used throughout this work and modified techniques in the handling of standard and analysis solution are described.

This procedure is well adapted for the use in routine analysis of potassium in ashed urine and feces samples.
Infrared Method for the Determination of Alpha (2-4-6), Beta (2-3-4), Gamma (2-4-5) Trinitrotoluene and 2–4 Dinitrotoluene in Admixtures Such as Found in TNT Exudates
Authors: Pristera Frank
Published: November 2005

An infrared method has been developed for the determination of alpha, beta, gamma Trinitrotoluene (TNT) and 2–4 Dinitrotoluene (DNT) in admixture. The method has been applied to synthetic mixtures where the alpha TNT ranged from 70 to 94% and the beta TNT, gamma TNT and 2–4 DNT each ranged from 2 to 10%. The average differences between the values found and the true values were as follows:

Alpha TNT — 1.24% Beta TNT — 0.23% Gama TNT — 0.19%; 2–4 DNT — 0.08%. The method involves making absorbance measurements of a 25% solution of the sample in benzene at the peaks of the 9.23, 9.36, 11.57 and 12.44 micron bands which are respectively those of alpha TNT, 2–4 DNT, gamma TNT and beta TNT. The measured absorbances, after being corrected for solvent and cell absorbance, were calculated to percent of alpha, beta, gamma TNT and 2–4 DNT by the method of successive approximations.
Applicability of Controlled Atmosphere Excitation to Spectrographic Methods of Analysis of Aluminum Alloys from Compacted Chips
Authors: Goldspiel S. , Bernstein F.
Published: November 2005

For further improvement of reproducibility of intensity ratios of constituent vs. aluminum lines, noted when argon atmospheres were used in the spark excitation of aluminum alloy (Alcoa 24S) chip compacts,1 a study was made of the effects of the following factors: chip size, carbon bonding, shape of pellet, sample pellet to sample pellet and to carbon electrode forms. The results show that unbonded, flat tipped pellets to carbon counter-electrodes produce the most desirable combination. Chip size does not have a significant influence on the results.

Analytical working curves for Mn, Mg, and Si covering the percentage ranges found in Alcoa types 14S, 17S, A17S and 24S were obtained for flat pellet versus pellet and versus carbon electrode forms. The slopes of all curves for the latter combinations are essentially the same as those for working curves obtained by the use of the conventional solid aluminum disc vs. carbon counter-electrode in air. Lateral shifts of curves for pellets in argon are in a direction indicating a decrease in energies available to neutral atom transitions. Standard errors of estimate, except for Mn, are nearly twice those for the conventional technique indicating need of additional improvement in the pellet form and size for more reproducible sample material.
The Application of Infrared Spectrophotometry to Quantitative Measurements: Statistical Studies of Absorption Intensity Reproducibility
Authors: Bowman Harry M. , Tarpley William B.
Published: November 2005

Because of its imporatnce in quantitative measurements, the degree of reproducibility of infrared absorption intensity measurements during one day, from day to day, and over an extended time interval of several months, has been studied.

Polystyrene films and wire screens were proved to have satisfactory stability for use as standard samples in this study.

Absorbance values used in this study were collected on a custom built double beam instrument as well as on two Perkin-Elmer double beam instruments. The data have been treated statistically. Comparable absorbance reproducibility was obtained with all three instruments but absorbance level shifts were observed.

Instrumental, operational and sample variables which contribute to lack of absorbance reproducibility have been considered. Recommendations are included which should interest instrument users as well as instrument producers.
The Equation of the Characteristic Curve of Photographic Emulsions
Authors: Green Milton
Published: November 2005

A general equation has been derived for the characteristic curve for the spectrographic level of illumination. This equation is relatively simple, fits the experimental curve very well, and although applied to only three types of emulsions so far, is believed to be applicable to most emulsions. This equation is log10D8/D= (I10/I)n (t10/t)q where D and D8 are density and saturation density, respectively; I and t are intensity and time, respectively; I10, t10, n and q are constants. D8, I10, n and q are all parameters of emulsion, wavelength and development.
The Design and Construction of a 22 Foot Direct-Reading Optical Spectrometer
Authors: Lee Ted
Published: November 2005

To meet a number of spectrochemical problems involving relatively complex spectra, a versatile grating spectrometer having high resolution and dispersion and using photomultiplier tubes to measure the intensities of the spectral lines was constructed. A concave diffraction grating having a radius of curvature of 21 feet 10 inches and ruled with 15,000 lines per inch over a 5 inch surface was used in an Eagle mounting designed to cover continuously the range from 2000 Ångstrom Units in the first order to 5800 Ångstrom Units in the fourth order. Five feet of spectrum are available at any setting of the instrument. To minimize backlash and spurious motion, kinematic principles were used in the design of the adjustments. Vibration absorbers and dampeners were used to minimize the effects of vibration, and constructing the instrument in a completely enclosed room located within an air-conditioned area minimized the effects of temperature changes. Either visual or photographic means may be used to position the exit slits and to adjust the optics. Both scanning and integration techniques are available.
Some Experimental Evidence of Collision Processes in Spectrochemical Analysis
Authors: Strock Lester W.
Published: November 2005

Synthetic silicate melts of CaSiOa and CaMg(SiO3)2 and 20 intermediate mixtures were used as standards for Calibrating a spectrochemical analysis method for CaO and MgO by the Ge metal dilution method previously described. The slope of log RET: log C curves showed large departures from unity, as follows: 0.82, 0.73, 0.62, and 0.24 respectively for Mg I 2779, Mg I 2776, Mg II 2795 and Mg II 2798. Curves for all Si lines showed slopes greater than unity: 1.27, 1.8, 4.22, and 6.39 respectively for Si I 2528, Si I 2987, Si I 2881, and Si I 2631. These results had earlier been interpreted as evidence for the effect of “collisions of the second kind” on intensity of light radiated by a DC arc source, whereby Mg and Si atoms collide and excitation energy is transferred from Mg to Si. Si intensity is enhanced and Mg weakened as the population of Mg atoms increases in the arc. The experimental log RET: log C curves are presented for the series of diopside: psuedo-wollastonite standards. The only variable in the standards is the MgO/CaO ratio. The amounts of these two substances vary such that their sum remains approximately constant. The Ge matrix and atmosphere are constant, and the SiO2 content is nearly so. Since the slopes of the Ca line curves are nearly unity, Mg and Si atoms are concluded to be involved in the energy exchanging collisions.
Mass Spectrometer Analyses Using a Viscous Leak
Authors: Mattraw H. C. , Patterson R. E. , Pachucki C. F.
Published: November 2005

Suitable dimensions of capillaries have been given which will provide continuous sampling of gas streams at 100–1000 mm(Hg). Methods of calibration of these capillaries (viscous leaks) for mass spectrometer analyses are presented.
Logarithmic Sector vs. Photoelectric Densitometer in Measuring Intensity Ratios
Authors: Green Milton , Polk Murray L.
Published: November 2005

The relative intensities of a group of ten lines of the spectrum of a hydrogen discharge tube have been measured both by conventional photoelectric densitometry and with a logarithmic sector. A statistical analysis of the results showed that, for our instruments, photoelectric densitometry is slightly more accurate than logarithmic sector intensitometry; the former method gave an average coefficient of variation, in the measurement of an intensity ratio, of 2% whereas the latter method gave an average coefficient of variation of approximately 4%. However, for a great many applications in spectrochemical analysis the latter method appears to be sufficiently accurate, at the same time having many advantages. It is faster, simpler; intensity ratios are obtained directly without the need of a calibration curve; the method is self calibrating; it does not involve a considerable amount of complicated equipment that requires frequent attention; intensity ratios can be made over a much greater range for a single exposure of the spectrum.
A Rapid Spectrographic Method for the Determination of Beryllium in Air Dust
Authors: Landis Frank P. , Coons Mary C.
Published: November 2005

A method has been developed for the determination of beryllium in air dust samples at the rate of 11 man-minutes per sample. The method involves the use of a small filter paper sample which is inserted into a -cupped graphite electrode and arced in a conventional direct current arc. Certain treatments are necessary to ensure optimum excitation of the sample, including the addition of a barium chloride carrier and internal standard. The method is sensitive to .002 microgram of beryllium on the filter paper, and the range of analysis extends to .1 microgram. The accuracy of the method is about ±30% of the amount of beryllium present.
Ultraviolet and Infrared Spectrophotometric Analysis of an Insect Repellent Mixture
Authors: Sassaman Warren A. , Cohen S. P.
Published: November 2005

A spectrophotometric procedure employing measurements in both the ultraviolet and infrared regions was developed to determine the concentrations of N-butyl acetanilide, benzyl benzoate, 2-ethyl, 2-butyl propanediol-1,3 and Tween 80, in a mixture containing only these four components.

The first two components have relatively strong absorptivities in the ultraviolet at 227.5 and 280.3 millimicrons, while the latter two have absorption bands at the infrared wavelengths, 8.99 and 9.60 microns. By substituting the absorptivities at these wavelengths in a set of four simultaneous equations, the percentage of each component in an insect repellent mixture is calculated.
The Carbon Effect in the Spectrographic Analysis of Refractory Materials
Authors: Ricard Raymond
Published: November 2005

The effect of adding graphite to mixtures of refractory powders volatilized in the crater of a carbon arc has been studied for various proportions of graphite. In general the lines of the less volatile elements, Al, Mg, Si, and Ti, are amplified. This may be due to the reduction of the refractory oxides by the graphite, and also to the inhibition by the graphite of globule formation in the crater, resulting in more rapid volatilization of the powder.
X-Ray Spectroscopic Determination of Columbium and Tantalum in Rare-Earth Ores
Authors: Mortimore D. M. , Romans P. A. , Tews J. L.
Published: November 2005

A method is presented in this paper for the analysis of columbium and tantalum in monazite or similar ores. This method involves the use of x-ray spectroscopic techniques employing the latest instrumentation.

The intensity of the columbium and tantalum spectra is calculated and related to corresponding zirconium and hafnium spectra as internal standards. These intensity ratios are then converted to concentrations by the use of typical working curves. The lower concentration limit is 0.05 percent for columbium and 0.2 percent for tantalum, and the standard deviation is approximately 5 percent at concentrations of 2 percent of either element. Single determinations can be made in 40 minutes.
The Spectrochemical Analysis of Beryllium in Ore, Air and Solutions
Authors: Kehres Paul W. , Poehlman Wm. J.
Published: November 2005

A spectrographic method is described for the determination of beryllium oxide in. beryl ore in the range of 6–12%. The sample is mixed with iron oxide, lithium carbonate and graphite, briquetted, and excited in the A.C. spark. The amount of beryllium is determined by comparing the density of Be 3321.343 to Fe 3021.073.

In addition, the method of Cholak and Hubbard for the determination of beryllium has been extended to a wide variety of industrial solutions and its sensitivity increased quantitatively to 0.00025-micrograms of Be per milliliter of solution.
The memory of immigration in Catalan nationalism
Authors: Cardús i Ros Salvador
Published: November 2005

The role of immigration on the crafting of Catalan national identity has, in general terms, been underestimated. Despite the arrival of as many as three million immigrants into Catalan society during the course of the twentieth century, this phenomenon and its contribution to the reinforcement
and survival of Catalan cultural uniqueness has not been recognized. This article argues that without immigration, Catalonia would potentially have suffered economic decadence, cultural irrelevance and political non-existence. The author seeks to construct a theoretical model of analysis of
the immigrant’s status dilution and the benefits of transforming immigration in a ‘place of memory’ for the Catalan national identity.
Stranger in a strange land: twenty years of living and writing in Catalonia
Authors: Tree Matthew
Published: November 2005

This article is a subjective account of the various problems involved in moving to a nationally ambiguous area such as Catalonia; and a discussion of the function of autobiographical writing for authors living abroad.
Neuronal L-Type Calcium Channels Open Quickly and Are Inhibited Slowly
Authors: Helton Thomas D. , Xu Weifeng , Lipscombe Diane
Published: November 2005

Neuronal L-type calcium channels are essential for regulating activity-dependent gene expression, but they are thought to open too slowly to contribute to action potential-dependent calcium entry. A complication of studying native L-type channels is that they represent a minor fraction of the whole-cell calcium current in most neurons. Dihydropyridine antagonists are therefore widely used to establish the contribution of L-type channels to various neuronal processes and to study their underlying biophysical properties. The effectiveness of these antagonists on L-type channels, however, varies with stimulus and channel subtype. Here, we study recombinant neuronal L-type calcium channels, CaV1.2 and CaV1.3. We show that these channels open with fast kinetics and carry substantial calcium entry in response to individual action potential waveforms, contrary to most studies of native L-type currents. Neuronal CaV1.3 L-type channels were as efficient as CaV2.2 N-type channels at supporting calcium entry during action potential-like stimuli. We conclude that the apparent slow activation of native L-type currents and their lack of contribution to single action potentials reflect the state-dependent nature of the dihydropyridine antagonists used to study them, not the underlying properties of L-type channels.
Neuronal Computation of Disparity in V1 Limits Temporal Resolution for Detecting Disparity Modulation
Authors: Nienborg Hendrikje , Bridge Holly , Parker Andrew J. , Cumming Bruce G.
Published: November 2005

The human ability to detect modulation of binocular disparity over time is poor compared with detection of luminance modulation. We examined the physiological origin of this limitation by analyzing neuronal responses to temporal modulation of binocular disparity in striate cortex of awake monkeys.

When neurons were presented with random-dot stereograms in which disparity varied sinusoidally over time, their responses modulated at the stimulus temporal frequency, with little change in mean firing rate. We calculated modulation amplitude as a function of temporal frequency and compared this with the psychophysical performance of four human observers. Neuronal and psychophysical functions showed similar peak frequencies (2 Hz) and comparable high-cut frequencies (10 and 5.5 Hz, respectively). Thus, V1 (primary visual cortex) neurons appear to limit psychophysical performance.

The temporal resolution of the same neurons for contrast modulation was ∼2.5 times greater, which parallels the superior psychophysical performance for contrast. There is a simple mathematical explanation for this difference: it results from calculating cross-correlation between temporally broadband monocular images that are bandpass filtered before measuring correlation.

The limit on temporal resolution is a direct consequence of the binocular energy model that adds to the list of properties of human stereoscopic performance that are explained by this simple model of disparity encoding in V1: the same neurons can account for the performance of psychophysical tasks that result in either high (contrast) or low (disparity) temporal resolution. Because this principle holds whenever a broadband input is bandpass filtered before computing correlation, it may limit the resolution of other neuronal systems.
Antidepressants and Antipsychotic Drugs Colocalize with 5-HT3Receptors in Raft-Like Domains
Authors: Eisensamer Brigitte , Uhr Manfred , Meyr Sabrina , Gimpl Gerald , Deiml Tobias , Rammes Gerhard , Lambert Jeremy J. , Zieglgänsberger Walter , Holsboer Florian , Rupprecht Rainer
Published: November 2005

Despite different chemical structure and pharmacodynamic signaling pathways, a variety of antidepressants and antipsychotics inhibit ion fluxes through 5-HT3receptors in a noncompetitive manner with the exception of the known competitive antagonists mirtazapine and clozapine. To further investigate the mechanisms underlying the noncompetitive inhibition of the serotonin-evoked cation current, we quantified the concentrations of different types of antidepressants and antipsychotics in fractions of sucrose flotation gradients isolated from HEK293 (human embryonic kidney 293) cells stably transfected with the 5-HT3Areceptor and of N1E-115 neuroblastoma cells in relation to the localization of the 5-HT3receptor protein within the cell membrane. Western blots revealed a localization of the 5-HT3receptor protein exclusively in the low buoyant density (LBD) fractions compatible with a localization within raft-like domains. Also, the antidepressants desipramine, fluoxetine, and reboxetine and the antipsychotics fluphenazine, haloperidol, and clozapine were markedly enriched in LBD fractions, whereas no accumulation occurs for mirtazapine, carbamazepine, moclobemide, and risperidone. The concentrations of psychopharmacological drugs within LBD fractions was strongly associated with their inhibitory potency against serotonin-induced cation currents. The noncompetitive antagonism of antidepressants at the 5-HT3receptor was not conferred by an enhancement of receptor internalization as shown by immunofluorescence studies, assessment of receptor density in clathrin-coated vesicles, and electrophysiological recordings after coexpression of a dominant-negative mutant of dynamin I, which inhibits receptor internalization. In conclusion, enrichment of antidepressants and antipsychotics in raft-like domains within the cell membrane appears to be crucial for their antagonistic effects at ligand-gated ion channels such as 5-HT3receptors.
Declarative Memory, Awareness, and Transitive Inference
Authors: Smith Christine , Squire Larry R.
Published: November 2005

A characteristic usually attributed to declarative memory is that what is learned is accessible to awareness. Recently, the relationship between awareness and declarative (hippocampus-dependent) memory has been questioned on the basis of findings from transitive inference tasks. In transitive inference, participants are first trained on overlapping pairs of items (e.g., A+B-, B+C-, C+D-, and D+E-, where + and - indicate correct and incorrect choices). Later, participants who choose B over D when presented with the novel pair BD are said to demonstrate transitive inference. The ability to exhibit transitive inference is thought to depend on the fact that participants have represented the stimulus elements hierarchically (i.e., A>B>C>D>E). We found that performance on five-item and six-item transitive inference tasks was closely related to awareness of the hierarchical relationship among the elements of the training pairs. Participants who were aware of the hierarchy performed near 100% correct on all tests of transitivity, but participants who were unaware of the hierarchy performed poorly (e.g., on transitive pair BD in the five-item problem; on transitive pairs BD, BE, and CE in the six-item problem). When the five-item task was administered to memory-impaired patients with damage thought to be limited to the hippocampal region, the patients were impaired at learning the training pairs. All patients were unaware of the hierarchy and, like unaware controls, performed poorly on the BD pair. The findings indicate that awareness is critical for robust performance on tests of transitive inference and support the view that awareness of what is learned is a fundamental characteristic of declarative memory.
Apoptosis-Inducing Factor Triggered by Poly(ADP-Ribose) Polymerase and Bid Mediates Neuronal Cell Death after Oxygen-Glucose Deprivation and Focal Cerebral Ischemia
Authors: Culmsee Carsten , Zhu Changlian , Landshamer Stefan , Becattini Barbara , Wagner Ernst , Pellecchia Maurizio , Blomgren Klas , Plesnila Nikolaus
Published: November 2005

Delayed neuronal cell death occurring hours after reperfusion is a hallmark of ischemic stroke and a primary target for neuroprotective strategies. In the present study, we investigated whether apoptosis-inducing factor (AIF), a caspase-independent proapoptotic protein, is responsible for neuronal cell death after glutamate toxicity and oxygen-glucose deprivation (OGD)in vitroand after experimental strokein vivo. AIF translocated to the nucleus in which it colocalized with DNA fragmentation and nuclear apoptotic morphology after exposure to glutamate or OGD in cultured neurons or after transient middle cerebral artery occlusion (MCAo) in mice. Small inhibitory RNA-mediated downregulation of AIF reduced glutamate- and OGD-induced neuronal apoptosis by 37 and 60%, respectively (p< 0.01). Moreover, Harlequin mutant mice, which express AIF at low levels (∼20% of wild-type mice), displayed smaller infarct volumes (-43%;p< 0.03) and showed dramatically reduced cell death in the ischemic penumbra after 45 min of MCAo compared with wild-type littermates. Inhibition of poly(ADP-ribose) polymerase and Bid reduced nuclear AIF translocation. These results provide the first evidence for a causal role of AIF in ischemic neuronal cell death. Therefore, caspase-independent cell death signaling may provide a promising novel target for therapeutic interventions in cerebrovascular diseases.
Neural Coupling Binds Visual Tokens to Moving Stimuli
Authors: Rose Michael , Büchel Christian
Published: November 2005

Spatially separated visual objects that appear in alternating sequence can be perceived as a single moving object. This phenomenon of apparent motion enables us to perceive sequentially presented images as a motion picture. How does the visual system bind together single visual tokens to one moving object? Here we report a series of experiments investigating apparent motion with electroencephalographic recordings showing that gamma-band oscillatory coupling in the visual cortex is crucial for this phenomenon. We used an ambiguous stimulus that could be perceived as moving either vertically or horizontally. Because visual information from the right and left visual hemifields is routed to the contralateral early visual cortex, in the case of perceived horizontal movement, information from both hemispheres has to be integrated. In accord with this assumption, our data show stronger oscillatory coupling between right and left visual cortices during perception of horizontal motion compared with vertical motion.
Dynamically Modulated Spike Correlation in Monkey Inferior Temporal Cortex Depending on the Feature Configuration within a Whole Object
Authors: Hirabayashi Toshiyuki , Miyashita Yasushi
Published: November 2005

The mechanism underlying the processing of spatially separated multiple local features to form a unique whole object is an important issue in visual object recognition. We tested whether, in behaving monkeys, the spike correlation between pairs of inferior temporal (IT) neurons dynamically changes depending on the spatial configuration of the local features within a whole object. We prepared more than 60,000 face-like objects (FOs) and their corresponding non-face-like objects (NFOs) that consisted of random arrangements of the same set of local features as those in FOs. The spike correlation between a pair of neurons was quantified by the peak height of the shift predictor-subtracted cross-correlogram. For both neurons of the pair, the local features in a whole object were determined so that they elicited as high a response as possible to enable a reliable cross-correlation analysis. We found that the FOs thus constructed elicited neuronal activities that were more strongly correlated than the corresponding NFOs. Firing rates of the same neurons did not show such a consistent bias depending on the feature configuration. Furthermore, receiver operating characteristic analysis revealed that this FO dominance of spike correlation was robust enough to discriminate between different feature configurations at the population level. Spike correlation of the cell pairs exhibited significant FO dominance within 300 ms after stimulus onset. The present results suggest that feature configuration within a unique whole object can be reflected in the rapid modulation of spike correlation among a population of neurons in the IT cortex.
Neuronal Differentiation in the Adult Hippocampus Recapitulates Embryonic Development
Authors: Espósito M. Soledad , Piatti Verónica C. , Laplagne Diego A. , Morgenstern Nicolás A. , Ferrari Carina C. , Pitossi Fernando J. , Schinder Alejandro F.
Published: November 2005

In the adult hippocampus and olfactory bulb, neural progenitor cells generate neurons that functionally integrate into the existing circuits. To understand how neuronal differentiation occurs in the adult hippocampus, we labeled dividing progenitor cells with a retrovirus expressing green fluorescent protein and studied the morphological and functional properties of their neuronal progeny over the following weeks. During the first week neurons had an irregular shape and immature spikes and were synaptically silent. Slow GABAergic synaptic inputs first appeared during the second week, when neurons exhibited spineless dendrites and migrated into the granule cell layer. In contrast, glutamatergic afferents were detected by the fourth week in neurons displaying mature excitability and morphology. Interestingly, fast GABAergic responses were the latest to appear. It is striking that neuronal maturation in the adult hippocampus follows a precise sequence of connectivity (silent → slow GABA → glutamate → fast GABA) that resembles hippocampal development. We conclude that, unlike what is observed in the olfactory bulb, the hippocampus maintains the same developmental rules for neuronal integration through adulthood.
Development of a Femtomolar-Acting Humanin Derivative Named Colivelin by Attaching Activity-Dependent Neurotrophic Factor to Its N Terminus: Characterization of Colivelin-Mediated Neuroprotection against Alzheimer's Disease-Relevant InsultsIn VitroandIn Vivo
Authors: Chiba Tomohiro , Yamada Marina , Hashimoto Yuichi , Sato Maiko , Sasabe Jumpei , Kita Yoshiko , Terashita Kenzo , Aiso Sadakazu , Nishimoto Ikuo , Matsuoka Masaaki
Published: November 2005

Alzheimer's disease (AD) is the most common cause of dementia. Humanin (HN) is a short bioactive peptide abolishing neuronal cell death induced by various familial AD (FAD)-causative genes and amyloid-β (Aβ)in vitro. It has been shown that HN suppresses memory impairment of mice induced by intracerebroventricular administration of Aβ. To potentiate the neuroprotective effect of HN, we synthesized a hybrid peptide named Colivelin composed of activity-dependent neurotrophic factor (ADNF) C-terminally fused to AGA-(C8R)HNG17, a potent HN derivative. Colivelin completely suppresses death induced by overexpressed FAD-causative genes and Aβ1-43 at a concentration of 100 fm, whereas AGA-(C8R)HNG17 does so at a concentration of 10 pm. Colivelin-induced neuroprotection has been confirmed to occur via two neuroprotective pathways: one mediated by Ca2+/calmodulin-dependent protein kinase IV, triggered by ADNF, and one mediated by signal transducer and activator of transcription 3, triggered by HN.In vivoanimal studies have further indicated that intracerebroventricular administration of Colivelin not only completely suppresses impairment in spatial working memory induced by repetitive intracerebroventricular injection of Aβ25-35 or Aβ1-42, but also it antagonizes neuronal loss in the CA1 region of hippocampus induced by hippocampal injection of Aβ1-42. In addition, intraperitoneally administered Colivelin suppresses memory impairment caused by a muscarinic acetylcholine receptor antagonist, 3-quinuclidinyl benzilate, indicating that a substantial portion of intraperitoneally administered Colivelin passes through the blood-brain barrier and suppresses functional memory deficit. Thus, Colivelin might serve as a novel drug candidate for treatment of AD.
A Population-Based Study to Determine the Performance of the Cognitive Adaptive Test/Clinical Linguistic and Auditory Milestone Scale to Predict the Mental Developmental Index at 18 Months on the Bayley Scales of Infant Development-II in Very Preterm Infants
Authors: Vincer Michael J. , Cake Heather , Graven Michael , Dodds Linda , McHugh Shelly , Fraboni Theresa
Published: November 2005

Objectives. To determine optimal ages to perform the Cognitive Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) and optimal “cutoff” score of the CAT/CLAMS to screen very preterm infants (<31 weeks) for severe cognitive-adaptive delay and to ascertain the sensitivity, specificity and likelihood ratios using optimal cutoff scores compared with the Mental Developmental Index (MDI) of the Bayley Scales of Infant Development II.

Methods. A population-based cohort of very preterm infants who were born to mothers who resided in Nova Scotia or Prince Edward Island were evaluated at 4, 8, 12, and 18 months’ corrected gestational age, which included a CAT/CLAMS by a physician. At 18 months’ corrected gestational age, each child was assessed using the Bayley Scales of Infant Development II, the “gold standard” for developmental delay in young infants. The results of each CAT/CLAMS was compared with the 18-month MDI to identify significant developmental delay (MDI <70).

Results. Optimal scores on the CAT/CLAMS to identify correctly MDI <70 were determined by using the κ statistic for chance independent agreement. Sensitivities and specificities for optimal cutoff scores were as follows: 4-month score <109 (88% and 37%), 8-month score <98 (75% and 82%), 12-month score <81 (63% and 99%), and 18-month score <83 (88% and 98%).

Conclusion. Sensitivity and specificity of the CAT/CLAMS are high in very preterm infants at identifying major developmental delay at 12 and 18 months. For follow-up programs without psychology services, the CAT/CLAMS at 12 and 18 months is a reasonable screening tool to determine which children need expedited psychology referral for cognitive delay.
I Could Live other Places, but This is Where I Want to Be: Support for Natural Helper Initiatives
Authors: DeBate Rita D. , Plescia Marcus
Published: November 2005

Charlotte REACH 2010 is an example of a multi-level intervention with the goal of reducing cardiovascular disease (CVD) and diabetes. Structured within a socio-ecological framework, lay health advisors are the link between the multi-level programs. An exploratory assessment was conducted using focus group methodology. Nine focus groups were conducted with the Charlotte REACH LHAs, residents who had participated in REACH program activities, and residents who had not participated in REACH activities. Results reveal two prominent themes: improvements in health practices and community competence. Both LHAs and community participants improved their knowledge of health enhancement behaviors, developed health enhancement skills and behaviors, and noted personal, familial, and community wide health improvements. Community competence was also observed with regard to community commitment, communication of health issues, and expanded social support networks. The results of this qualitative evaluation suggest the effectiveness of incorporating natural helper models as part of larger multi-level initiatives.
Factors Associated with Increased Risk for Acute Unintentional Childhood Poisoning among Children Living on the U.S.-Mexico Border
Authors: Roddy Mary E. , O'Rourke Kathleen M. , Mena Kristina
Published: November 2005

This study evaluated prevalence of unsafe storage of toxic products and evaluated the association of demographic-socio-cultural variables with risk of young-child exposure to household poisons. Interviews were conducted with 698 low-income caregivers living on the U.S./Mexico border. Multiple-ordinal regression was used to analyze associations between very unsafe storage of toxic products and household factors. At least one toxic product was accessible to children in 49.4% of households and 18.5% of these households' stored substances very unsafely in that products were accessible and stored either in non-original containers or without childproof caps. At-risk households were associated with U.S.-born caregivers who were single, employed, and live in more U.S. acculturated communities. These homes stored an increased number of toxins and were more likely to house a smoker. U.S./Mexico border childhood poisoning prevention programs should focus on potentially acculturated families with personal and household characteristics akin to the U.S. mores and customs.
A Qualitative Evaluation of Rural Community Coalitions
Authors: McFall Stephanie L. , Norton Barbara L. , McLeroy Kenneth R.
Published: November 2005

A multiple case study design was used to evaluate coalitions for community health improvement and promotion in Oklahoma. Data collection in three communities took place in two-day site visits; interviews were conducted with 42 persons. A coalition development model was used to analyze structure, activities and outcomes: mobilization, development of organizational structure, activities, member satisfaction, accomplishments, and maintenance. Each community mobilized a multi-sectoral Steering Committee with a simple organizational structure but had limited success in implementing its plans. The process was truncated in the third community. Member satisfaction was mixed. In particular, they expressed desire for more assistance in leveraging resources to enact their priorities. Because organizational structure and activities were consistent with project design, we attributed the limited success to program design choices. In particular, the organizational structure did not promote community leadership or member engagement.
A Scale to Assess Attitudes toward Euthanasia
Authors: Wasserman Jason , Clair Jeffrey Michael , Ritchey Ferris J.
Published: November 2005

The topic of euthanasia has been a matter of public debate for several decades. Although empirical research should inform policy, scale measurement is lacking. After analyzing shortcomings of previous work, we offer a systematically designed scale to measure attitudes toward euthanasia. We attempt to encompass previously unspecified dimensions of the phenomenon that are central to the euthanasia debate. The results of our pretest show that our attitude towards euthanasia (ATE) scale is both reliable and valid. We delineate active and passive euthanasia, no chance for recovery and severe pain, and patient's autonomy and doctor's authority. We argue that isolating these factors provides a more robust scale capable of better analyzing sample variance. Internal consistency is established with Cronbach's alpha = .871. Construct external consistency is established by correlating the scale with other predictors such as race and spirituality.
Molecular Dynamics Simulations of Gas Phase Condensation of Silicon Carbide Nanoparticles
Authors: Erhart P. , Albe K.
Published: November 2005

Gas phase condensation of silicon and silicon carbide nanoparticles is studied by molecular‐dynamics simulations. By using a recently developed bond‐order potential for Si, C and SiC we investigate the fundamental processes governing nucleation and growth of SiC nanoparticles. For the case of elemental silicon particles we show that variations in the binding energy of dimers, which represent stable nuclei for the condensation process, significantly affect the long time evolution of the cluster formation process. A detailed analysis of the molecular reactions during the early stages of SiC particle growth is presented. Reactions, in which silicon monomers are formed, are dominant in case of stoichiometric composition of the precursor gas. Moreover, we find the formation of carbon‐dominated species to be preferred and a sensitive dependence of the particle composition and morphology on the processing conditions, especially the cooling and precursor gas composition.
Relevance for browsing, relevance for searching
Authors: Bodoff David
Published: November 2005

The concept of relevance has received a great deal of theoretical attention. Separately, the relationship between focused search and browsing has also received extensive theoretical attention. This article aims to integrate these two literatures with a model and an empirical study that relate relevance in focused searching to relevance in browsing. Some factors affect both kinds of relevance in the same direction; others affect them in different ways. In our empirical study, we find that the latter factors dominate, so that there is actually a negative correlation between the probability of a document's relevance to a browsing user and its probability of relevance to a focused searcher.