bluuebunny/crossref_metadata_2025 huggingface dataset:
A Comparison of Infants' Categorization in Paired and Successive Presentation Familiarization Tasks
Authors: Oakes Lisa M. , Ribar Rebecca J.
Published: February 2005

Three experiments directly compared infants' categorization in variations of the visual familiarization task. In each experiment, 4‐ or 6‐month‐old infants were familiarized with a collection of dogs or cats and then their response to novel dogs and cats was assessed. In Experiment 1, 4‐month‐old infants responded to the exclusive distinction of dogs or cats when tested in a paired‐comparison task. In Experiments 2 and 3, 6‐month‐old infants, but not 4‐month‐old infants, responded to this same distinction in a successive presentation task, even when the amount of familiarization was equated to that of the paired comparison task. Therefore, familiarization with a particular set of stimuli does not induce infants to respond to a single category but rather they respond to different categories depending on features of the task.
Homo- and heteromeric assembly of TRPV channel subunits
Authors: Hellwig Nicole , Albrecht Nadine , Harteneck Christian , Schultz Günter , Schaefer Michael
Published: February 2005

The vanilloid receptor-related TRP channels (TRPV1-6) mediate thermosensation, pain perception and epithelial Ca2+ entry. As the specificity of TRPV channel heteromerization and determinants governing the assembly of TRPV subunits were largely elusive, we investigated the TRPV homo- and heteromultimerization. To analyze the assembly of TRPV subunits in living cells, we generated fluorescent fusion proteins or FLAG-tagged TRPV channel subunits. The interaction between TRPV subunits was assessed by analysis of the subcellular colocalization, fluorescence resonance energy transfer and coimmunoprecipitation. Our results demonstrate that TRPV channel subunits do not combine arbitrarily. With the exception of TRPV5 and TRPV6, TRPV channel subunits preferentially assemble into homomeric complexes. Truncation of TRPV1, expression of cytosolic termini of TRPV1 or TRPV4 and construction of chimeric TRPV channel subunits revealed that the specificity and the affinity of the subunit interaction is synergistically provided by interaction modules located in the transmembrane domains and in the cytosolic termini. The relative contribution of intramolecularly linked interaction modules presumably controls the overall affinity and the specificity of TRPV channel assembly.
Loss of α10β1 integrin expression leads to moderate dysfunction of growth plate chondrocytes
Authors: Bengtsson Therese , Aszodi Attila , Nicolae Claudia , Hunziker Ernst B. , Lundgren-Åkerlund Evy , Fässler Reinhard
Published: February 2005

Integrin α10β1 is a collagen-binding integrin expressed on chondrocytes. In order to unravel the role of the α10 integrin during development, we generated mice carrying a constitutive deletion of the α10 integrin gene. The mutant mice had a normal lifespan and were fertile but developed a growth retardation of the long bones. Analysis of the skeleton revealed defects in the growth plate after birth characterized by a disturbed columnar arrangement of chondrocytes, abnormal chondrocyte shape and reduced chondrocyte proliferation. Electron microscopy of growth plates from newborn mice revealed an increased number of apoptotic chondrocytes and reduced density of the collagen fibrillar network compared to these structures in control mice. These results demonstrate that integrin α10β1 plays a specific role in growth plate morphogenesis and function.
Large-scale chromatin decondensation induced in a developmentally activated transgene locus
Authors: Wegel Eva , Vallejos Ruben H. , Christou Paul , Stöger Eva , Shaw Peter
Published: February 2005

The high molecular weight (HMW) glutenin-encoding genes in wheat are developmentally activated in the endosperm at about 8 days after anthesis. We have investigated the physical changes that occur in these genes in two transgenic lines containing about 20 and 50 copies each of the HMW glutenin genes together with their promoters. Using fluorescence in-situ hybridisation (FISH) and confocal imaging, we demonstrate that, in non-expressing tissue, each transgene locus consists of one or two highly condensed sites, which decondense into many foci upon activation of transcription in endosperm nuclei. Initiation of transcription can precede decondensation but not vice versa. We show that, in one of the lines, cytoplasmic transcript levels are high after onset of transcription but disappear by 14 days after anthesis, whereas small interfering RNAs, which indicate post-transcriptional gene silencing (PTGS), are detected at this stage. However, the transcript levels remain high at the transcription sites, most of the transgene copies are transcriptionally active and transcriptional activity in the nucleus ceases only with cell death at the end of endosperm development.
Pigment epithelium-derived factor inhibits fibroblast-growth-factor-2-induced capillary morphogenesis of endothelial cells through Fyn
Authors: Kanda Shigeru , Mochizuki Yasushi , Nakamura Takao , Miyata Yasuyoshi , Matsuyama Toshifumi , Kanetake Hiroshi
Published: February 2005

Pigment epithelium-derived factor (PEDF) exerts anti-angiogenic actions. However, the signal-transduction pathways regulated by PEDF remain to be elucidated. We show here that PEDF inhibited fibroblast growth factor 2 (FGF-2) induced capillary morphogenesis of a murine brain capillary endothelial cell line (IBE cells) and of human umbilical-vein endothelial cells (HUVECs) cultured on growth-factor-reduced Matrigel. We previously showed that FGF-2-mediated capillary morphogenesis was blocked by the Src-kinase inhibitor PP2 and that expression of dominant negative Fyn in IBE cells inhibited capillary morphogenesis. We examined the effect of PEDF on kinase activity of Fyn and found that PEDF downregulated FGF-2-promoted Fyn activity by tyrosine phosphorylation at the C-terminus in a Fes-dependent manner. In a stable IBE cell line expressing kinase-inactive Fes (KE5-15 Fes cells), PEDF failed to inhibit FGF-2-induced capillary morphogenesis or Fyn activity. PEDF induced the colocalization of Fyn and Fes in IBE cells expressing wild-type Fes, but not in KE5-15 Fes cells. In addition, wild-type Fes increased the tyrosine phosphorylation of Fyn in vitro, suggesting that Fes might directly phosphorylate Fyn. Expression of constitutively active Fyn (Y531F) in IBE cells exhibited capillary morphogenesis in the absence of FGF-2 and was resistant for PEDF treatment. Our results suggest that PEDF downregulates Fyn through Fes, resulting in inhibition of FGF-2-induced capillary morphogenesis of endothelial cells.
Norfloxacin-Induced Toxic Epidermal Necrolysis
Authors: Sahin Mustafa Turhan , Ozturkcan Serap , Inanir Isil , Filiz Elif E
Published: February 2005

OBJECTIVE:

To report a case of toxic epidermal necrolysis (TEN) in a man who was treated with oral norfloxacin for prostatitis.

CASE SUMMARY:

A 40-year-old man presented with a severe skin reaction, which was diagnosed as TEN. He had received norfloxacin 800 mg/day over a 14-day period for prostatitis and, 10 days after finishing the treatment regimen, he developed cutaneous and mucous lesions typical of TEN. After a prolonged hospitalization and treatment with oral prednisolone therapy, fluid resuscitation, and wound dressing, the man recovered.

DISCUSSION:

TEN is an infrequent, yet often fatal, severe systemic and cutaneous disease that is most often an adverse drug reaction. There are few case reports of TEN induced by fluoroquinolones. A MEDLINE search (1966–February 2005) revealed no reports of toxic epidermal necrolysis, but one incidence of Stevens—Johnson syndrome due to norfloxacin therapy. An objective causality assessment suggests that TEN was probably related to norfloxacin in this patient.

CONCLUSIONS:

To our knowledge, this is the first case of TEN associated with the use of oral norfloxacin. We hope that this case report creates awareness that norfloxacin-induced TEN is possible.
Low Trough Plasma Concentrations of Nevirapine Associated with Virologic Rebounds in HIV-Infected Patients Who Switched from Protease Inhibitors
Authors: Duong Michel , Buisson Marielle , Peytavin Gilles , Kohli Evelyne , Piroth Lionel , Martha Benoit , Grappin Michèle , Chavanet Pascal , Portier Henri
Published: February 2005

BACKGROUND:

The substitution of a nonnucleoside reverse-transcriptase inhibitor (NNRTI) for protease inhibitors (PIs) has demonstrated its suitability to maintain virologic response. However, the switch from PIs to an NNRTI could fail for a number of reasons, including NNRTI-associated toxicity and emergence of NNRTI-resistant variants.

OBJECTIVE:

To describe the virologic failures among 74 HIV-infected patients who switched from PIs to nevirapine.

METHODS:

Virologic failure was defined as any rebound of the plasma HIV-RNA (pVL) levels >1000 copies/mL on one occasion or 2 consecutive intermittent viremia episodes defined as increases of the pVL >20 copies/mL but <1000 copies/mL. Virologic failures were investigated retrospectively by determining nevirapine trough concentrations and performing genotypic resistance analysis.

RESULTS:

The mean nevirapine concentration was significantly lower in patients with virologic failure in comparison with patients with virologic response (2572 ± 1642 vs 4550 ± 2084 ng/mL, respectively; p = 0.003). In multivariate analysis, the mean duration of undetectable pVL before the switch and the mean plasma concentration of nevirapine were significantly associated with virologic success with relative rates of 1.39 (95% CI 1.10 to 1.76, p = 0.006) and 2.7 (95% CI 1.37 to 5.41, p = 0.01), respectively. In patients with pVL >1000 copies/mL, nevirapine mutations and nucleoside reverse-transcriptase inhibitor mutations were found in 80% of the cases.

CONCLUSIONS:

The risk of virologic failure after the switch from PI to nevirapine is higher in cases of inadequate nevirapine plasma concentrations. Our data support prospective monitoring of nevirapine plasma concentrations to detect low concentrations prior to the emergence of resistance mutations.
New Developments in Planar Array Infrared Spectroscopy
Authors: Pelletier Isabelle , Pellerin Christian , Chase D. Bruce , Rabolt John F.
Published: February 2005

A planar array infrared (PA-IR) spectrograph offers several advantages over other infrared approaches, including high acquisition rate and sensitivity. However, it suffers from some important drawbacks, such as a limited spectral range and a significant curvature of the recorded spectral images, which still need to be addressed. In this article, we present new developments in PA-IR spectroscopy that overcome these drawbacks. First, a data processing method for the correction of the curvature observed in the spectral images has been developed and refined. In addition, a dual-beam instrument that allows the simultaneous recording of two independent spectral images has been developed. These two improvements have been combined to demonstrate the real-time background correction capability of PA-IR instruments. Finally, the accessible spectral range of the PA-IR spectrograph has been extended to cover simultaneously the methylene stretching (3200–2800 cm−1) and the fingerprint (2000–1000 cm−1) spectral regions.
Noninvasive Alcohol Testing Using Diffuse Reflectance Near-Infrared Spectroscopy
Authors: Ridder T. D. , Hendee S. P. , Brown C. D.
Published: February 2005

A diffuse reflectance near-infrared (NIR) spectrometer was evaluated as a noninvasive alternative to breath and blood measurements for in vivo alcohol testing. A hybrid partial least squares (PLS) calibration was constructed using a combination of in vivo and in vitro spectral data. This model was subsequently evaluated for its performance in quantifying alcohol concentrations in vivo using a prospective validation study involving subjects who did not participate in the calibration. The validation study entailed induction of alcohol excursions in ten human subjects and comparison of the noninvasive NIR alcohol measurements to blood and breath alcohol measurements. Blood and breath alcohol measurements were performed at the time of each noninvasive NIR measurement ( N = 372), establishing the noninvasive NIR measurement standard error relative to blood alcohol at 4.9 mg/dL (0.0049%). Assessment of the hybrid calibration model's sensitivity and selectivity provided strong evidence that the hybrid calibration yielded measurements that were both sensitive to alcohol and independent of other absorbing analytes in human tissue.
Relative Contributions of Hemoglobin and Myoglobin to Near-Infrared Spectroscopic Images of Cardiac Tissue
Authors: Nighswander-Rempel Stephen P. , Kupriyanov Valery V. , Shaw R. Anthony
Published: February 2005

Near-infrared (NIR) spectroscopic imaging is emerging as a unique tool for intra-operative assessment of myocardial oxygenation, but quantitative interpretation of the images is not straightforward. One confounding factor specific to muscle tissue (both skeletal and cardiac) is that the visible/NIR absorbance spectrum of myoglobin (Mb), an intracellular O2 storage protein, is virtually identical to that of hemoglobin (Hb). As a consequence, the relative contributions of Mb and Hb to the NIR spectra measured in vivo for blood perfused muscle tissue cannot be determined from the measured spectra alone. To estimate the relative contributions of Mb and Hb to NIR spectra and spectroscopic images, isolated pig hearts were perfused first with a Hb-free blood substitute (Krebs-Henseleit buffer; KHB) and then with a 50/50 KHB/blood mixture, with spectroscopic images acquired at each step. Tissue Mb levels were estimated directly from the measurements during KHB perfusion, and total (Mb+Hb) levels were estimated from the images acquired during 50/50 blood/KHB perfusion. Myoglobin accounted for 63 ± 11% of the total heme content during perfusion with the 50/50 mixture (implying that Mb would contribute 46% of the combined (Mb+Hb) NIR profile during whole blood perfusion), confirming that Mb contributes substantially to near-infrared absorbance spectra of blood perfused cardiac tissue.
High-Throughput Single-Cell Fluorescence Spectroscopy
Authors: Isailovic Dragan , Li Hung-Wing , Phillips Gregory J. , Yeung Edward S.
Published: February 2005

A high-throughput method for measuring single-cell fluorescence spectra is presented. Upon excitation with a 488 nm argon-ion laser many bacterial cells were imaged by a 20× microscope objective while they moved through a capillary tube. Fluorescence was dispersed by a transmission diffraction grating, and an intensified charge-coupled device (ICCD) camera simultaneously recorded the zero and the first orders of the fluorescence from each cell. Single-cell fluorescence spectra were reconstructed from the distance between zero-order and first-order maxima as well as the length and the pixel intensity distribution of the first-order images. By using this approach, the emission spectrum of E. coli cells expressing green fluorescent protein (GFP) was reconstructed. Also, fluorescence spectra of E. coli cells expressing non-fluorescent apo-subunits of R-phycoerythrin (R-PE) were recorded after incubation of the cells with phycoerythrobilin (PEB) chromophore. The fluorescence spectra are in good agreement with results obtained on the same cells using a fluorescence spectrometer or a fluorescence microscope. When spectra are to be acquired, this approach has a higher throughput, better sensitivity, and better spectral resolution compared to flow cytometry.
Trace Element Analysis of Scales from Four Populations of Norwegian Atlantic Salmon (Salmo Salar L.) for Stock Identification Using Laser Ablation Inductively Coupled Plasma Mass Spectrometry
Authors: Flem Belinda , Moen Vidar , Grimstvedt Andreas
Published: February 2005

The pre-smolt stage of the scale of adult Norwegian Atlantic salmon from four populations, encompassing both farmed and wild hatchery stocks, has been analyzed by laser ablation inductively coupled plasma mass spectrometry (LA-HR-ICP-MS). The purpose of this study was to test for differences in elemental composition between stocks of Atlantic salmon that have lived in separate fresh water locations until the smoltification and natural run out or transportation to the sea-cages. The populations studied were from fish farms located at Bremanger and Sørfold, a cultivated stock from Mossa, and one wild local stock from the river Gaula. The following elements were included in the analytical protocol: Li, Mg, Ca, Cr, Mn, Fe, Zn, Sr, Ba, Pb, and U. Calcium was used as a natural internal standard. Classification of the analytical data is studied by multivariate statistical techniques such as principal component analysis (PCA). We have been able to delineate the population of Atlantic salmon ( Salmo salar L.) from Gaula and Mossa from the Bremanger and the Sørfold stock based on the ten elements analyzed. The Bremanger and Sørfold stocks were partially delineated. The differences in elemental composition in the scales, which makes the delineating of the four stocks possible, probably reflects geological differences in the bedrock at the four fresh water locations experienced by the salmon during the pre-smolt stage.
Textual and visual interfaces in art and design education
Authors: Orr Susan , Blythman Margo , Mullin Joan
Published: February 2005

This guest-edited edition continues to explore the themes that were addressed in Volume 3 Number 2 by focusing on textual and visual interfaces in art and design education. Students studying in an art and design curriculum create, design and write. They are assessed via the textual
and the visual. Because of the scale and quality of the response to the call for papers we have brought to you two editions that address this theme. The authors in this edition – Volume 3 Number 3 – are introduced to readers in the editorial in Volume 3 Number 2.
The tetrahedron can encourage designers to formalize more responsible strategies
Authors: Wood John
Published: February 2005

This article will outline a non-linear method of writing that I have been developing since 1990. It assumes that academic writing is a productive way to explore and guide the practice of design, and that this is important for environmental and other reasons. Today’s designers
play a key role in helping us to attain the kind of lifestyle to which all societies are now encouraged to aspire. Enabling them to deepen the way they think would have positive long-term benefits. The auto-didactic potential of writing is well known, but I believe it can also be applied to
help designers to become more self-reflexively in touch with their entrepreneurial and professional roles in the world.
Laboratory Tests on the Rate of Piping Erosion of Soils in Embankment Dams
Authors: Wan CF , Fell R
Published: February 2005

The Slot Erosion Test and the Hole Erosion Test have been developed as fast and simple tests for studying the erosion characteristics of soil in cracks in embankment dams. The erosion characteristics are described by the Erosion Rate Index, which measures the increase of erosion rate with respect to an increase in the hydraulic shear stress; and the Initial Shear Stress, which represents the minimum hydraulic shear stress when erosion starts. Knowledge of these erosion characteristics aids in the prediction of the likelihood of embankment dam failure due to piping erosion in a risk assessment process.

Values of the Erosion Rate Index span from 0 to 6, indicating that the changes in erosion rates in response to changes in hydraulic shear stress can differ by up to 106 times across different soils. The Erosion Rate Index is apparently influenced by the soil fines and clay-sized content, plasticity, dispersivity, water content, dry density, degree of saturation, clay mineralogy, and possibly the presence of cementing materials such as iron oxides. Coarse-grained, noncohesive soils, in general, erode more rapidly and have lower Initial Shear Stresses than fine-grained soils.
Estimation of Stress Field Near a Notch Root of 3-D Structures with a Few Strain Data and the Body Force Method
Authors: Yoshimura T , Harada T , Noguchi H , Yoshimura T
Published: February 2005

A method is proposed for estimating stress fields using a few surface strain data, obtained either from strain gages or from finite-element analysis (FEA), and the body force method (BFM). A notch in a three-dimensional structural surface is considered to be an observed domain. The observed domain is treated as a pseudo-3-D plate, not a part of a 3-D body. In other words, the body force is distributed in the observed domain to add a 3-D influence to a plane stress problem. In this paper, the results by elastic finite-element method (FEM) analysis are used instead of the strain gage outputs on actual structures to investigate the application limit of the present method. It is possible to obtain the maximum stress value within 10% error by self-assessment of the result with the present method.
Stress Concentration Factor Formulas Useful for Any Dimensions of Shoulder Fillet in a Flat Test Specimen Under Tension and Bending
Authors: Noda NA , Takase Y
Published: February 2005

In this work stress concentration factors Kt for a flat bar with fillets are considered on the basis of exact solutions now available for special cases and accurate numerical results. Then, a convenient Ktformula useful for any dimensions of the fillet is proposed. The conclusions can be summarized as follows.

1. For the limiting cases of deep (d) and shallow (s) fillets, the body force method is used to calculate the Ktvalues. Then, the formulas are obtained as Ktd and Kts.

2. On the one hand, upon comparison of Kt and Ktd, it is found that Kt is nearly equal to Ktd if the fillet is deep or blunt.

3. On the other hand, if the fillet is sharp or shallow, Kt is controlled mainly by Kts and the fillet depth.

4. The fillet shape is classified into several groups according to the fillet radius and fillet depth. Then, the least-squares method is applied for calculation of Kt/Ktd and Kt/Kts.

5. Finally, convenient formulas are proposed that are useful for any dimensions of fillet in a flat bar. The formulas give SCFs with less than about 1 % error in most cases for any dimensions of fillet under tension and bending.
Residual Stress Measurement in Ion-Exchanged Glass by Iterated Birefringence and Etching
Authors: Abrams M , Shen J , Green D
Published: February 2005

Residual stresses play an important role in controlling fracture behavior in ion-exchanged glass. In this work, the internal tensile stress resulting from ion exchange is measured using conventional birefringence methods. By progressively etching thin layers from the glass surface, the compressive stress in the removed layer can then be determined from the change in the compensating internal tensile stress, producing a stress profile as a function of depth. Specimen geometry, surface roughness, and configuration of the optical system are examined in order to improve the accuracy of the method.
Characteristics of Macrodeformation Behavior of the Cycling Failure Specimens of a Fe-Cr-Ni Alloy Under In-phase and Out-of-phase Thermomechanical Fatigue
Authors: He Q , Qian Y
Published: February 2005

Characteristics of macrodeformation behavior of the cycling failure specimens of a Fe-Ni-Cr alloy were studied under in-phase and out-of-phase synchronization of thermal cycling with mechanical cycling. Varied hysteresis loops characterize different cycling hardening behavior under in-phase and out-of-phase thermomechanical fatigue (TMF). Out-of-phase caused stronger hardening and severe asymmetry of cycling stress leading to a shorter failure life. Meanwhile thermomechanical cycling weakening hardening behavior occurred in the higher temperature region in each cycling. Asymmetry of the configuration change of the specimen is evident under Out-of-phase.
UV Absorber Permanence and Coating Lifetimes
Authors: Pickett JE
Published: February 2005

Delamination is the ultimate failure mechanism of a coating. Delamination times often are closely related to the dose of ultraviolet (UV) radiation reaching the substrate or primer, and this dose is related to the UV absorbing capability of the overlying coating. Organic UV absorbers are not permanent, and their photodegradation is an important factor in determining coating lifetime. The kinetics and some of the chemistry of UV absorber photodegradation have been studied extensively over the past decade and applied to coating lifetime prediction. Rates of UV absorber loss vary widely and are highly dependent on the coating matrix, so must be determined on a case-by-case basis. Simple zero- or first-order kinetic schemes give rates that are dependent on the initial absorbance of the sample. This paper discusses a more reliable kinetic equation and applies the rate constant to prediction of delamination times.
Gq/11-Induced and Spontaneous Waves of Coordinated Network Activation in Developing Frontal Cortex
Authors: Calderon D. Paola , Leverkova Natalya , Peinado Alejandro
Published: February 2005

Repeated episodes of spontaneous large-scale neuronal bursting and calcium influx in the developing brain can potentially affect such fundamental processes as circuit formation and gene expression. Between postnatal day 3 (P3) and P7, the immature cortex can express one such form of activation whereby a wave of neuronal activity propagates through cortical networks, generating massive calcium influx. We previously showed that this activity could be triggered by brief stimulation of muscarinic receptors. Here, we show, by monitoring large cortical areas at low magnification, that although all areas respond to muscarinic agonists to some extent, only some areas are likely to generate the coordinated wave-like activation. The waves can be triggered repeatedly in frontal areas where, as we also show, waves occur spontaneously at a low frequency. In parietal and occipital areas, no such waves are seen. This selectivity may be related in part to differences in the cortical distribution of dopaminergic signaling, because we find that activation of dopamine receptors enables the response. Because M1 muscarinic receptors are typically coupled with G-αq/11, we investigated whether other receptors known to couple with this G-protein (group I glutamate metabotropic receptors, neurotensin type 1) could similarly elicit wave-like activation in responsive cortical areas. Our results suggest that multiple neurotransmitter systems can enable this form of activation in the frontal cortex. The findings suggest that a poorly recognized, developmentally regulated form of strong network activation found predominantly in the frontal cortex could potentially exert a profound influence on brain development.
Neurotensin Activates GABAergic Interneurons in the Prefrontal Cortex
Authors: Petrie Kimberly A. , Schmidt Dennis , Bubser Michael , Fadel Jim , Carraway Robert E. , Deutch Ariel Y.
Published: February 2005

Converging data suggest a dysfunction of prefrontal cortical GABAergic interneurons in schizophrenia. Morphological and physiological studies indicate that cortical GABA cells are modulated by a variety of afferents. The peptide transmitter neurotensin may be one such modulator of interneurons. In the rat prefrontal cortex (PFC), neurotensin is exclusively localized to dopamine axons and has been suggested to be decreased in schizophrenia. However, the effects of neurotensin on cortical interneurons are poorly understood. We usedin vivomicrodialysis in freely moving rats to assess whether neurotensin regulates PFC GABAergic interneurons. Intra-PFC administration of neurotensin concentration-dependently increased extracellular GABA levels; this effect was impulse dependent, being blocked by treatment with tetrodotoxin. The ability of neurotensin to increase GABA levels in the PFC was also blocked by pretreatment with 2-[1-(7-chloro-4-quinolinyl)-5-(2,6-dimethoxyphenyl)pyrazole-3-yl)carbonylamino]tricyclo(3.3.1.1.3.7)decan-2-carboxylic acid (SR48692), a high-affinity neurotensin receptor 1 (NTR1) antagonist. This finding is consistent with our observation that NTR1 was localized to GABAergic interneurons in the PFC, particularly parvalbumin-containing interneurons. Because neurotensin is exclusively localized to dopamine axons in the PFC, we also determined whether neurotensin plays a role in the ability of dopamine agonists to increase extracellular GABA levels. We found that D2agonist-elicited increases in PFC GABA levels were blocked by pretreatment with SR48692, consistent with data indicating that D2autoreceptor agonists increase neurotensin release from dopamine-neurotensin axons in the PFC. These findings suggest that neurotensin plays an important role in regulating prefrontal cortical interneurons and that it may be useful to consider neurotensin agonists as an adjunct in the treatment of schizophrenia.
Role of Synaptic and Intrinsic Membrane Properties in Short-Term Receptive Field Dynamics in Cat Area 17
Authors: Nowak Lionel G. , Sanchez-Vives Maria V. , McCormick David A.
Published: February 2005

We examined the mechanisms through which the prolonged presentation of either a high-contrast stimulus or an artificial scotoma [equivalent to the stimulation of the receptive field (RF) surround] induces changes in the RF properties of neurons intracellularly recorded in cat primary visual cortex. Discharge and synaptic RFs were quantitatively characterized using bright and dark bars randomly flashed in various positions. Compared with the lack of stimulation (0% contrast for 15-30 s), stimulation with high-contrast sine-wave gratings (15-30 s) was followed by a strong reduction in gain and a weak but significant reduction in width of spike discharge RFs. These reductions were accompanied by a membrane potential hyperpolarization, a decrease of synaptic RF width, and varying changes of synaptic RF gain. Passive hyperpolarization by DC injection also produced significant reduction in the width and gain of discharge RF. Mimicking, in single neurons, high-contrast stimulation with high-intensity current injection also induced a membrane potential hyperpolarization, whose amplitude was correlated with discharge RF gain and width changes. Recovery from adaptation to high-contrast stimulation during the period of gray screen or scotoma presentation was associated with an increase in gain and discharge RF size. Stimulation of the RF surround with an artificial scotoma did not have any additional aftereffects over those of adaptation to a gray screen, indicating that the contraction and expansion of RF gain and size are attributable to intrinsic and synaptic mechanisms underlying adaptation and de-adaptation to strong visual stimuli.
Toll-Like Receptor 4 on Nonhematopoietic Cells Sustains CNS Inflammation during Endotoxemia, Independent of Systemic Cytokines
Authors: Chakravarty Sumana , Herkenham Miles
Published: February 2005

Inflammatory agonists such as lipopolysaccharide (LPS) induce robust systemic as well as CNS responses after peripheral administration. Responses in the innate immune system require triggering of toll-like receptor 4 (TLR4), but the origin of CNS sequelas has been controversial. We demonstrate expression of TLR4 transcripts in mouse brain in the meninges, ventricular ependyma, circumventricular organs, along the vasculature, and in parenchymal microglia. The contribution of TLR4 expressed in CNS resident versus hematopoietic cells to the development of CNS inflammation was examined using chimeric mice. Reciprocal bone marrow chimeras between wild-type and TLR4 mutant mice show that TLR4 on CNS resident cells is critically required for sustained inflammation in the brain after systemic LPS administration. Hematopoietic TLR4 alone supported the systemic release of acute phase cytokines, but transcription of proinflammatory genes in the CNS was reduced in duration. In contrast, TLR4 function in radiation-resistant cells was sufficient for inflammatory progression in the brains of chimeric mice, despite the striking absence of cytokine elevations in serum. Surprisingly, a temporal rise in serum corticosterone was also dependent on TLR4 signaling in nonhematopoietic cells. Our findings demonstrate a requirement for TLR4 function in CNS-resident cells, independent of systemic cytokine effects, for sustained CNS-specific inflammation and corticosterone rise during endotoxemia.
Overexpression of GD1a Ganglioside Sensitizes Motor Nerve Terminals to Anti-GD1a Antibody-Mediated Injury in a Model of Acute Motor Axonal Neuropathy
Authors: Goodfellow John A. , Bowes Tyrone , Sheikh Kazim , Odaka Masaaki , Halstead Susan K. , Humphreys Peter D. , Wagner Eric R. , Yuki Nobuhiro , Furukawa Koichi , Furukawa Keiko , Plomp Jaap J. , Willison Hugh J.
Published: February 2005

Anti-GD1a ganglioside antibodies (Abs) are the serological hallmark of the acute motor axonal form of the post-infectious paralysis, Guillain-Barré syndrome. Development of a disease model in mice has been impeded by the weak immunogenicity of gangliosides and the apparent resistance of GD1a-containing neural membranes to anti-GD1a antibody-mediated injury. Here we used mice with altered ganglioside biosynthesis to generate such a model at motor nerve terminals. First, we bypassed immunological tolerance by immunizing GD1a-deficient, β-1,4-N-acetylgalactosaminyl transferase knock-out mice with GD1a ganglioside-mimicking antigens fromCampylobacter jejuniand generated high-titer anti-GD1a antisera and complement fixing monoclonal Abs (mAbs). Next, we exposedex vivonerve-muscle preparations from GD1a-overexpressing, GD3 synthase knock-out mice to the anti-GD1a mAbs in the presence of a source of complement and investigated morphological and electrophysiological damage. Dense antibody and complement deposits were observed only over presynaptic motor axons, accompanied by severe ultrastructural damage and electrophysiological blockade of motor nerve terminal function. Perisynaptic Schwann cells and postsynaptic membranes were unaffected. In contrast, normal mice were not only unresponsive to immunization with GD1a but also resistant to neural injury during anti-GD1a Ab exposure, demonstrating the central role of membrane antigen density in modulating both immune tolerance to GD1a and axonal susceptibility to anti-GD1a Abmediated injury. Identical paralyzing effects were observed when testing mouse and human anti-GD1a-positive sera. These data indicate that anti-GD1a Abs arise via molecular mimicry and are likely to be clinically relevant in injuring peripheral nerve axonal membranes containing sufficiently high levels of GD1a.
Ectopic Norrin Induces Growth of Ocular Capillaries and Restores Normal Retinal Angiogenesis in Norrie Disease Mutant Mice
Authors: Ohlmann Andreas , Scholz Michael , Goldwich Andreas , Chauhan Bharesh K. , Hudl Kristiane , Ohlmann Anne V. , Zrenner Eberhart , Berger Wolfgang , Cvekl Aleš , Seeliger Mathias W. , Tamm Ernst R.
Published: February 2005

Norrie disease is an X-linked retinal dysplasia that presents with congenital blindness, sensorineural deafness, and mental retardation. Norrin, the protein product of the Norrie disease gene (NDP), is a secreted protein of unknown biochemical function. Norrie disease (Ndpy/-) mutant mice that are deficient in norrin develop blindness, show a distinct failure in retinal angiogenesis, and completely lack the deep capillary layers of the retina. We show here that the transgenic expression of ectopic norrin under control of a lens-specific promoter restores the formation of a normal retinal vascular network inNdpy/-mutant mice. The improvement in structure correlates with restoration of neuronal function in the retina. In addition, lenses of transgenic mice with ectopic expression of norrin show significantly more capillaries in the hyaloid vasculature that surrounds the lens during development.In vitro, lenses of transgenic mice in coculture with microvascular endothelial cells induce proliferation of the cells. Transgenic mice with ectopic expression of norrin show more bromodeoxyuridine-labeled retinal progenitor cells at embryonic day 14.5 and thicker retinas at postnatal life than wild-type littermates, indicating a putative direct neurotrophic effect of norrin. These data provide direct evidence that norrin induces growth of ocular capillaries and that pharmacologic modulation of norrin might be used for treatment of the vascular abnormalities associated with Norrie disease or other vascular disorders of the retina.
Spontaneous Release of Neuropeptide Y Tonically Inhibits Recurrent Mossy Fiber Synaptic Transmission in Epileptic Brain
Authors: Tu Bin , Timofeeva Olga , Jiao Yiqun , Nadler J. Victor
Published: February 2005

In the pilocarpine model of temporal lobe epilepsy, mossy fibers coexpress the inhibitory transmitter neuropeptide Y (NPY) with glutamate. The effects of endogenous and applied NPY on recurrent mossy fiber synaptic transmission were investigated with the use of whole-cell voltage-clamp and field recordings in rat hippocampal slices. Applied NPY reversibly inhibited synaptic transmission at recurrent mossy fiber synapses on dentate granule cells but not at perforant path or associational-commissural synapses. It also reduced the frequency of miniature EPSCs (mEPSCs) in granule cells from epileptic, but not control, rats and depressed granule cell epileptiform activity dependent on the recurrent mossy fiber pathway. These actions of NPY were mediated by activation of presynaptic Y2receptors. The Y2receptor antagonist (S)-N2-[[1-[2-[4-[(R,S)-5,11-dihydro-6(6H)-oxodibenz[b,e]azepin-11-yl]-1-piperazinyl]-2-oxoethyl]cyclopentyl]acetyl]-N-[2-[1,2-dihydro-3,5(4H)-dioxo-1,2-diphenyl-3H-1,2,4-triazol-4-yl]ethyl]argininamide (BIIE0246) not only blocked the effects of NPY but also enhanced recurrent mossy fiber synaptic transmission, the frequency of mEPSCs, and the magnitude of mossy fiber-evoked granule cell epileptiform activity when applied by itself. Several observations supported the selectivity of BIIE0246. These results suggest that even the spontaneous release of NPY (or an active metabolite) from recurrent mossy fibers is sufficient to depress glutamate release from this pathway. Tonic release of NPY accounts at least partially for the low probability of glutamate release from recurrent mossy fiber terminals, impedes the ability of these fibers to synchronize granule cell discharge, and may protect the hippocampus from seizures that involve the entorhinal cortex. This pathway may synchronize granule cell discharge more effectively in human brain than in rat because of its lower expression of NPY.
Remarkable Solvent Effects of Oxygen- and Sulfur-Containing Compounds on the Propagation Rate of Methyl Methacrylate
Authors: Harrisson Simon , Barner-Kowollik Christopher , Davis Thomas P. , Evans Richard , Rizzardo Ezio , Stenzel Martina , Yin Ming
Published: February 2005

The propagation kinetics of methyl methacrylate (MMA) in the presence of a number of oxygen- and sulfur-containing compounds have been investigated. Solvents used were 2-methyl-1,3-dioxepane (MDOP), 2,6-dithiaheptane (DTHP) and 1,5-dithiacyclooctane (DTCO). In the presence of DTHP and DTCO, the propagation rate coefficient, k
p, of MMA was found to be 25% to 100% higher compared to bulk polymerisations under the same conditions. The significant increase of k
p was explained by electron donation from the sulfur-containing solvents, which increased the reactivity of the macroradicals. MDOP had no observable effect on k
p. The solvent influence on polymer tacticity was also studied using both 1H and 13C NMR spectroscopy. No significant influence of the solvent on polymer tacticity was found.
Encounter Rate of Chemically Reactive Species in Highly Diluted Polymer Solutions Investigated by Fluorescence Quenching
Authors: Schlepegrell Andreas , Rynka Stephan , Adams Jörg , Fuhrmann Jürgen
Published: February 2005

Stern–Volmer constant is used as a criterion for a diffusion controlled encounter rate and studied in the time domain around 100 ns and in the distance domain around 30 nm in highly diluted polystyrene-cyclohexane solutions at θ-temperature. By choice of the θ-situation the thermodynamic influence on the encounter rate is small and the Stokes–Einstein hydrodynamics prevails within the investigated time and distance domain. The internal viscosity at the overlap concentration depends on molecular weight like the segmental density of the polymer does in this homogeneous situation. In highly diluted situation the molecular weight effect levels off if the center of mass distance gets larger than twice the coil diameter. This is illustrated by a cell model combined with a cell specific obstacle model.
Influence of Salts During Hydrothermal Biomass Gasification: The Role of the Catalysed Water-Gas Shift Reaction
Authors: Kruse Andrea , Dinjus Eckhard
Published: February 2005

Near-critical and supercritical water is an unusual reaction medium with extraordinary properties, varying with temperature and density. This opens the opportunity for new reactions and new technical processes. In the studies of synthesis reactions, total oxidation and biomass gasification interesting effects of salts are observed. These effects are assumed to be caused by complex formation, acidity/basicity or the presence of active hydrogen due to the water-gas shift reaction. The water-gas shift reaction is catalysed by salts and lead to the formation of hydrogen, which might react with other compounds.

This article focuses on the salt effects during hydrogen production by biomass gasification in supercritical water. This is a very interesting process to make use of “wet biomass”, which is up to now not applied in a technical process. Here salts influenced the main reactions pathways. Possible reasons are discussed.
Dimerization of Pyrazole in Slit Jet Expansions
Authors: Rice Corey A. , Borho Nicole , Suhm Martin A.
Published: February 2005

Pyrazole dimer is observed for the first time in a free jet expansion. Its IR-active N–H stretching vibration is shifted by −269 cm−1 relative to the monomer. Along the 600 mm slit jet expansion, the average number density of pyrazole dimers is ∼ 1011 cm−3. Exploratory quantum chemical calculations including electron correlation are in good agreement with the observed frequency shift and confirm reciprocal hydrogen bonding with bent hydrogen bonds in a planar C2

h
structure, as postulated by W. Hückel 65 years ago in this journal. Nanomatrix isolation spectra can be obtained by using Ar as the carrier gas. The more strongly coupled vibrational dynamics in pyrazole trimer is illustrated.
Pump–Probe Spectroscopy of Cycloheptatriene: Transient Anisotropy and Isotope Effect
Authors: Hippler H. , Olzmann Matthias , Schalk O. , Unterreiner A.-N.
Published: February 2005

Internal conversion processes of 1,3,5-cycloheptatriene (CHT) and its perdeuterated counterpart (CHT-d8) in liquid cyclohexane have been studied by performing pump–probe experiments. The excitation and probe wavelength were 263 nm and 395 nm, respectively; the time resolution was 50 fs. Temporal absorption and transient anisotropy profiles were monitored. The experimental findings are consistent with the following mechanism: After excitation, the system undergoes a fast internal conversion associated with a molecular reorientation. The characteristic times are (110±10) fs for CHT and (150±20) fs for CHT-d8. The transient anisotropy as well as the isotope effect are consistent with a [1,7] hydrogen shift as reorientation mechanism. Moreover, initial anisotropies indicate that coherence effects between two excited states at early times may occur.
Bilateral Assimilation of Two Neighboring Empty Time Intervals
Authors: Miyauchi Ryota , Nakajima Takayuki
Published: February 2005

In many sensory dimensions, assimilation of characteristics of perceived events can be found. In the present study, we examined whether assimilation appeared also in time perception, employing time intervals shorter than 300 ms marked by tone bursts. In Experiment 1, we measured points of subjective equality of two neighboring empty time intervals, t1 and t2. The perceived durations approached each other when the difference between t1 and t2 was small. That is, bilateral assimilation took place. In Experiment 2, we measured points of subjective equality of t1 in smaller steps and across a wider durational range than in Experiment 1. We found that t1 was overestimated slightly when it was a bit shorter than t2, and t1 was underestimated slightly when it was a bit longer than t2. The overestimation and the underestimation were considered as typical assimilation. The results also showed that the perception of t1 changed from assimilation to contrast when the difference between t1 and t2 exceeded the range -80 � t1 � t2 � 40 ms.
Timing of Action During and After Synchronization With Linearly Changing Intervals
Authors: Madison Guy , Merker Bj�rn
Published: February 2005

Musicians and nonmusicians synchronized drum-beating movements to sound sequences composed of 90 successive interonset intervals that increased or decreased continually by various amounts of time. After the end of a sequence, they continued to produce 30 beats without interruption. Synchronization appeared both smooth and accurate for all levels of changing tempo. In general, actions preceded sounds with increasing intervals and lagged behind sounds with decreasing intervals, indicating that the stimulus change was not fully predicted. There was a tendency for the continuation intervals to change in the reverse direction of the preceding synchronization intervals, suggesting that the system retains information about the tempo change. We discuss these results in terms of the demands tempo change makes on timing mechanisms, and what they reveal about participants� ability to create and sustain an internal nonisochronous periodic process.
Keeping Synchrony While Tempo Changes: Accelerando and Ritardando
Authors: Schulze Hans-Henning , Cordes Andreas , Vorberg Dirk
Published: February 2005

We studied synchronization with a metronome that smoothly changes tempo, from slow to fast (accelerando) or from fast to slow (ritardando). During the transition phase, systematic alternations of underadjustment and overadjustment of period and phase were observed. We analyzed the synchronization error (�asynchrony�) sequences in terms of two models that both assume linear period and phase correction mechanisms but differ in terms of how the timekeeper period is adjusted to the tempo change. In the interval-based model, period corrections are based on comparisons between timekeeper and metronome intervals, whereas in the asynchrony-based model, period corrections are based on the deviations of taps from metronome events. The qualitative data pattern is more compatible with an asynchrony-based model than with an interval-based model. Additional mechanisms that switch on and off period adjustment seem to be needed, however, for a quantitative fit of this model to our data.
Rate Limits of On-Beat and Off-Beat Tapping With Simple Auditory Rhythms: 1. Qualitative Observations
Authors: Repp Bruno H.
Published: February 2005

The accuracy of on-beat and off-beat synchronized finger tapping was examined as a function of sequence rate in musically trained individuals. Auditory sequences consisted of cyclically repeated, underlyingly isochronous patterns of the form T0, TT0, or TTT0, where T denotes a tone onset and 0 denotes its absence. In different conditions, participants attempted to tap in synchrony with one of the possible T (�on-beat�) or 0 (�off-beat�) positions in each pattern while the sequence rate increased from trial to trial. It was hypothesized that on-beat tapping would be easier with tones that carry a rhythmic grouping accent (T2 in TT0, T1 and T3 in TTT0) than with tones that do not (T1 in TT0, T2 in TTT0), according to findings of Povel and colleagues. The hypothesis was strongly supported for TTT0, but there were considerable individual differences with regard to TT0. Off-beat tapping was generally difficult and often switched to on-beat tapping at fast tempi. The findings reveal rate limits of sensorimotor coordination that may be relevant to music performance in ensembles.