bluuebunny/crossref_metadata_2025 huggingface dataset:
Real-time completion monitoring with acoustic waves
Authors: Bakulin Andrey , Sidorov Alexander , Kashtan Boris , Jaaskelainen Mikko
Published: December 2007

Deepwater production is challenged by well underperformance issues that are hard to diagnose early on and expensive to deal with later. Problems are amplified by reliance on a few complex wells with sophisticated sand-control media. New downhole data are required for better understanding and prevention of production impairment. We introduce real-time completion monitoring (RTCM), a new nonintrusive surveillance method that uses acoustic signals sent via the fluid column to identify permeability impairment in sand-screened completions. The signals are carried by tube waves that move borehole fluid back and forth radially across the completion layers. Such tube waves are capable of instant testing of the presence or absence of fluid communication across the completion and are sensitive to changes occurring in sand screens, gravel sand, perforations, and possibly in the reservoir. The part of the completion that has different impairment from its neighbors will carry tube waves with modified signatures (velocity, attenuation) and will produce a reflection from the boundary where impairment changes. We conduct a laboratory experiment with a model of a completed horizontal borehole and focus on effects of sand-screen permeability on transmitted and reflected acoustic signatures. These new findings form the basis of an RTCM method that can be thought of as “miniaturized” 4D seismic and as a “permanent log” in an individual wellbore. We present experiments with a fiber-optic acoustic system that suggest a nonintrusive way to install downhole sensors on the pipe in realistic completions and thus implement real-time surveillance with RTCM.
Quantitative thickness estimates from the spectral response of AVO measurements
Authors: Nowak Ethan J. , Swan Herbert W. , Lane Dave
Published: December 2007

This study is motivated by the necessity to quantitatively characterize subtuned reservoirs. The conventional autocorrelation-based spectral-decomposition technique uses frequency notches to calculate vertical traveltime thickness of a layer of dipole reflectivity. Those notches tend to move outside the usable frequency band of the seismic data as the layer exceeds the tuning threshold of the wavelet. Assuming wavelet stationarity and nondipole reflectivity, a similar analysis performed on a crosscorrelation between an intercept and gradient trace extends the resolution limits to one-half the tuning threshold. That is a major improvement; however, many economic reservoirs still do not meet the half-tuning requirement. Such thin reservoirs led to the development of an optimization scheme. This approach, which does not require any wavelet stationarity or reflectivity assumptions, theoretically is not limited by the thickness of the target interval. The optimization scheme was applied successfully to a marine seismic survey in an attempt to estimate the traveltime thickness of a chalk reservoir.
Characteristics of males over 50 years who present with a fracture
Authors: Sharma S. , Fraser M. , Lovell F. , Reece A. , McLellan A. R.
Published: December 2007

Osteoporosis and fragility fractures in men constitute a considerable burden in healthcare. We have reviewed 2035 men aged over 50 years with 2142 fractures to clarify the epidemiology of these injuries and their underlying risk factors. The prevalence of osteoporosis ranged between 17.5% in fractures of the ankle and 57.8% in those of the hip. The main risk factors associated with osteoporosis were smoking (47.4%), alcohol excess (36.2%), body mass index < 21 (12.8%) and a family history of osteoporosis (8.4%). Immobility, smoking, self-reported alcohol excess, a low body mass index, age ≥72 and loss in height were significantly more common among men with fractures of the hip than in those with fractures elsewhere.
Clinical outcome after anatomical reconstruction of the lateral ankle ligaments using the Duquennoy technique in chronic lateral instability of the ankle
Authors: Muijs S. P. J. , Dijkstra P. D. S. , Bos C. F. A.
Published: December 2007

We performed a retrospective study to assess the long-term outcome of non-augmented anatomical direct repair of the lateral ankle ligaments, as originally described by Duquennoy et al, for the treatment of chronic lateral instability of the ankle. This procedure aims to restore stability by the re-insertion and tightening of the original talofibular and calcaneofibular ligaments without division of the ligament. We examined the outcome in terms of the post-operative quality of life, the function of the joint and the development of osteoarthritis.

Between 1985 and 2002, 23 patients (11 males, 12 females) with a mean age of 32 years (15 to 58) who had undergone this procedure completed the Short-Form 36 assessment of quality of life and the Olerud and Molander Ankle score for the subjective evaluation of symptoms. Clinical re-evaluation, including examination of the ankle and the completion of the American Orthopaedic Foot and Ankle Society questionnaire was performed on 21 patients after a mean follow-up of 13 years (3 to 22.2). At the final follow-up radiographs of both ankles were taken to assess the development of osteoarthritis.

The mean total Short-Form 36 and Olerud and Molander Ankle scores in 23 patients at final follow-up were 79.6 points (37 to 100) and 81.6 points (40 to 100), respectively. The mean total post-operative American Orthopaedic Foot and Ankle Society score in 21 patients was 89.7 points (72 to 100). We found a significant post-operative reduction in talar tilt and anterior drawer sign (chi-squared test, p < 0.001). The functional outcome of the procedure was excellent in ten patients (48%), good in seven (33%) and fair in four (19%). The results in terms of ankle function and stability did not deteriorate with time and there was little restriction in movement.

This procedure is simple and effective with a very low rate of complications.
Reattachment of the distal tendon of biceps
Authors: Kettler M. , Tingart M. J. , Lunger J. , Kuhn V.
Published: December 2007

Operative fixation is the treatment of choice for a rupture of the distal tendon of biceps. A variety of techniques have been described including transosseous sutures and suture anchors. The poor quality of the bone of the radial tuberosity might affect the load to failure of the tendon repair in early rehabilitation.

The aim of this study was to determine the loads to failure of different techniques of fixation and to investigate their association with the bone mineral density of the radial tuberosity.

Peripheral quantitative computed tomography was carried out to measure the trabecular and cortical bone mineral density of the radial tuberosity in 40 cadaver specimens. The loads to failure in four different techniques of fixation were determined.

The Endobutton-based method showed the highest failure load at 270 N (sd 22) (p < 0.05). The mean failure load of the transosseous suture technique was 210 N (sd 66) and that of the TwinFix-QuickT 5.0 mm was 57 N (sd 22), significantly lower than those of all other repairs (p < 0.05). No significant correlation was seen between bone mineral density and loads to failure.

The transosseous technique is an easy and cost-saving procedure for fixation of the distal biceps tendon. TwinFix-QuickT 5.0 mm had significantly lower failure loads, which might affect early rehabilitation, particularly in older patients.
Changing incidence of slipped capital femoral epiphysis
Authors: Murray A. W. , Wilson N. I. L.
Published: December 2007

Obesity is thought to be an aetiological factor for slipped capital femoral epiphysis (SCFE). We analysed changes in the incidence of SCFE in Scotland over the last two decades. During this period rates of childhood obesity have risen substantially and evidence for a relationship between these changes and the incidence of SCFE was sought.

We found that the incidence of SCFE increased from 3.78 per 100 000 children in 1981 to 9.66 per 100 000 in 2000 (R2= 0.715): a two and a half times increase over two decades. It was seen at a younger age, with a fall in the mean age at diagnosis from 13.4 to 12.6 years for boys (p = 0.007) and 12.2 to 11.6 for girls (p = 0.047). More children under eight years old were seen with SCFE in Scotland in the decade to 2000 than in the previous decade (p = 0.002, R2= 0.346).

A close correlation was observed between rising childhood obesity over the last 20 years in Scotland and an increasing incidence of SCFE.
The relationship of the medially-offset stem of the tibial component to the medial tibial cortex in total knee replacements in Korean patients
Authors: Yoo J. H. , Kang Y. G. , Chang C. B. , Seong S. C. , Kim T. K.
Published: December 2007

We examined the placement of the stem in relation to the medial tibial cortex when using total knee replacements (TKRs) with medially-offset tibial stems in Korean patients. Measurements were performed on the pre- and post-operative radiographs of 246 osteoarthritic knees replaced between January 2005 and May 2006 using the Genesis II or E-motion TKR with a medially-offset stem. Pre-operatively, we measured the distance between the mechanical axis and that of the tibial shaft and post-operatively, that between the midline of the tibial stem and the axis of the shaft.

Knees were identified in which there was radiological contact between the tip of the stem and the medial tibial cortex. The mechanical axis was located medial to the axis of the shaft in 203 knees (82.5%). Post-operatively, the midline of the tibial stem was located medial to the tibial shaft axis in 196 knees (79.7%). In 16 knees (6.5%) there was radiological contact between the tibial stem or cement mantle and the medial tibial cortex.

Our study has shown that the medially-offset stem in the tibial component may not be a good option for knees undergoing replacement for advanced osteoarthritis in some Korean patients.
Cyclical sciatica
Authors: Mannan K. , Altaf F. , Maniar S. , Tirabosco R. , Sinisi M. , Carlstedt T.
Published: December 2007

We describe a case of sciatic endometriosis in a 25-year-old woman diagnosed by MRI and histology with no evidence of intrapelvic disease.

The presentation, diagnosis and management of this rare condition are described. Early diagnosis and treatment are important to prevent irreversible damage to the sciatic nerve.
External fixation devices in the treatment of fractures of the tibial plafond
Authors: Papadokostakis G. , Kontakis G. , Giannoudis P. , Hadjipavlou A.
Published: December 2007

We have compared the outcomes of the use of external fixation devices for spanning or sparing the ankle joint in the treatment of fractures of the tibial plafond, focusing on the complications and the rates of healing. We have devised a scoring system for the quality of reporting of clinical outcomes, to determine the reliability of the results.

We conducted a search of publications in English between 1990 and 2006 using the Pubmed search engine. The key words used were pilon, pylon, plafond fractures, external fixation. A total of 15 articles, which included 465 fractures, were eligible for final evaluation.

There were no statistically significant differences between spanning and sparing fixation systems regarding the rates of infection, nonunion, and the time to union. Patients treated with spanning frames had significantly greater incidence of malunion compared with patients treated with sparing frames. In both groups, the outcome reporting score was very low; 60% of reports involving infection, nonunion or malunion scored 0 points.
Orthogonal Sample Design Scheme for Two-Dimensional Synchronous Spectroscopy and its Application in Probing Intermolecular Interactions
Authors: Qi Jian , Li Huizhen , Huang Kun , Chen Huhe , Liu Shaoxuan , Yang Limin , Zhao Ying , Zhang Chengfeng , Li Weihong , Wu Jinguang , Xu Duanfu , Xu Yizhuang , Noda Isao
Published: December 2007

This paper introduces a new approach to probing intermolecular interactions based on a framework of two-dimensional (2D) synchronous spectroscopy. Mathematical analysis performed on 2D synchronous spectra using variable concentration as an external perturbation shows that the cross-peaks are composed of two parts. The first part reflects intermolecular interactions that manifest in the form of deviation from the Beer–Lambert law. The second part is related simply to the concentration variations of the solutes and is responsible for the generation of interfering cross-peaks not related to the intermolecular interactions in the system. It is the second part that prevents the reliable identification of intermolecular interactions. We propose a way of selecting the concentrations of solutes so that the resultant dynamic concentration vectors of different solutes become orthogonal to one another. Therefore, the contribution of the second part to the cross-peaks can be effectively removed by the dot product of orthogonal vectors. Our new approach has been tested on a simulated chemical system and a real chemical system. The results demonstrate that interfering cross-peaks can be successfully removed from a 2D synchronous spectrum so that the cross-peaks can be used as a reliable tool to characterize or probe intermolecular interactions.
A Chromatographic Approach for Fluorescence Reduction in Liquid Raman Analysis
Authors: Afseth Nils Kristian , Segtnan Vegard Herman , Wold Jens Petter , Marquardt Brian J.
Published: December 2007

In this study a chromatographic approach for fluorescence reduction in liquid Raman analysis has been evaluated. The idea behind the approach is to apply a chromatographic separation step prior to Raman analysis in order to separate fluorescing compounds from other components of interest, thus facilitating better quantitative and qualitative analysis of the latter components. A real-time liquid-core Raman waveguide detector designed for chromatographic applications was used in the study, thus providing real-time chemical pretreatment of liquid samples for Raman analysis. Twenty aqueous mixtures of additives frequently found in beverages were analyzed, and for comparative purposes the mixtures were also analyzed in the Raman waveguide detector without chromatographic separation and with a conventional immersion probe. Both qualitatively and quantitatively satisfying results were obtained using the chromatographic Raman approach, and the technique provided possibilities for quantitative and qualitative assessments superior to the two other instrumental setups. The technique may provide additional benefits through sensitivity enhancements, and the approach is simple, inexpensive, and easy to implement in the average applied Raman laboratory. The analysis of various chemical systems and factors such as system stability over time need further evaluation in order to confirm the general applicability of the approach.
Application of Surface-Enhanced Infrared Absorption Spectroscopy to Investigate Pyridine Adsorption on Platinum-Group Electrodes
Authors: Li Qiao-Xia , Xue Xiao-Kang , Xu Qun-Jie , Cai Wen-Bin
Published: December 2007

In situ surface-enhanced infrared absorption spectroscopy (SEIRAS) was applied to investigate adsorption configurations of pyridine (Py) on platinum, palladium, ruthenium, and rhodium nanoparticle film electrodes. The results reveal that α-pyridyl species predominantly form on Pt electrodes by assuming an edge-on configuration with its ring N and α-C atoms bonding to the Pt surface, while on Ru and Rh electrodes pyridine molecules essentially remain intact by adopting a slightly edge-tilted configuration through bonding with its N lone pair electrons. Py adsorption on a Pd electrode may lie in between the above two cases; both α-pyridyl species and edge-tilted intact pyridine could be significantly present. Further comparison of the typical adsorption configurations on the above four electrodes with those on Ag, Au, Cu, Cd, and Ni film electrodes suggests that valence electrons and the periodic row of metals may play an important role in determining the adsorption configuration.
Polarization Properties of Oblique Incidence Scanning Tunneling Microscopy—Tip-Enhanced Raman Spectroscopy
Authors: Picardi Gennaro , Nguyen Quang , Ossikovski Razvigor , Schreiber Joachim
Published: December 2007

We used scanning tunneling microscopy–tip-enhanced Raman spectroscopy (STM-TERS) to study the polarization properties of near-field scattering on a crystalline material as well as on a dye adsorbate. The measurements on a (111)-oriented c-Si sample were found to be well described by a recently proposed model for TERS and allowed for a characterization of the polarization properties of the tips used. The tip enhancement was stronger for excitation radiation having a field component along the tip axis for both types of samples. A non-negligible enhancement was also found for the field component perpendicular to the tip axis.
Retrieval of Linear Optical Functions from Finite Range Spectra
Authors: Meneses Domingos De Sousa , Rousseau Benoit , Echegut Patrick , Simon Patrick
Published: December 2007

There are many experimental situations in which infrared reflectivity spectra can be acquired only over a limited spectral range. It is therefore necessary to find computing procedures that allow the efficient analysis of such data. In this paper, we propose a new procedure labeled constrained finite range correction (CFRC) that can be advantageously substituted to multiply subtractive Kramers–Kronig relations. The constrained finite range correction is able to produce realistic results even when very little supplementary information is available. For semitransparent crystals, the hypothesis of the phase spectrum positiveness alone is often sufficient to compute satisfactory approximations of the optical functions. The efficiency of the new method is shown through the analysis of several synthetic and experimental spectra.
The Multi-Reconstruction Entropy Minimization Method: Unsupervised Spectral Reconstruction of Pure Components from Mixture Spectra, without the Use of a Priori Information
Authors: Zhang Huajun , Chew Wee , Garland Marc
Published: December 2007

The band-target entropy minimization method (BTEM) and its variant methods excel at reconstructing known/unknown pure spectra from mixtures without prior information. These mixtures may represent either non-reactive or even reactive systems. In this work, an unsupervised form of the entropy minimization curve resolution, namely, the multi-reconstruction entropy minimization method (MREM), is presented. MREM differs from BTEM by removing the need for band-targets and by introducing a multiple search routine to find multiple local entropy minima. This multiple search routine, which provides a rapid survey of spectral estimates, utilizes a localized form of Corona's simulated annealing method in the optimization. The objective functions and penalty functions of the BTEM type methods are essentially retained. Compared to BTEM type methods, MREM (1) searches for multiple local minima instead of a single global minimum and hence reconstructs many pure component spectra at once instead of one pure spectrum; and (2) utilizes a user-defined broad spectral range [ν1, ν2] for all searches instead of multiple user-defined narrow “targets” as in BTEM. The new MREM has been tested on four sets of real spectra using Fourier transform infrared spectroscopy (FT-IR), mass spectroscopy (MS), and ultraviolet–visible (UV-Vis) spectroscopy. The results show that MREM is computationally much faster than BTEM for finding the major components present. Also, because MREM does not rely on band targeting, it is very useful for spectra that have no localized features and are highly overlapping, such as UV-Vis.
Fiber-Optic Spark Delivery for Gas-Phase Laser-Induced Breakdown Spectroscopy
Authors: Dumitrescu Cosmin , Puzinauskas Paulius , Olcmen Semih , Buckley Steven G. , Joshi Sachin , Yalin Azer P.
Published: December 2007

This article reports what are to the authors' knowledge the first gas-phase laser-induced breakdown spectroscopy (LIBS) measurements using a fiber-optically delivered spark. A silver- and polymer-coated hollow fiber delivered high-energy nanosecond 1064 nm Nd:YAG laser pulses, which were focused to generate high-energy-density plasmas in ultra-lean methane–air mixtures. Emissions from these plasmas were collected and spectroscopically analyzed to quantify relative fuel-to-air ratio. These measurements were compared with others made using traditional LIBS techniques without the fiber-optically delivered spark. Similar results were obtained, but with larger shot-to-shot variability, for the case of the fiber-optically delivered spark.
Influence of 5,10-Methylenetetrahydrofolate Reductase Polymorphism on Whole-Blood Folate Concentrations Measured by LC-MS/MS, Microbiologic Assay, and Bio-Rad Radioassay
Authors: Fazili Zia , Pfeiffer Christine M , Zhang Mindy , Jain Ram B , Koontz Deborah
Published: December 2007

Background: The 5,10-methylenetetrahydrofolate reductase (NADPH) (MTHFR) C677T polymorphism may affect whole-blood folate pattern measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and total folate measured by LC-MS/MS, microbiologic assay, and Bio-Rad radioassay (BR).

Methods: We analyzed 171 whole blood hemolysates from 2 blood banks for folate pattern and total folate concentrations using these 3 methods and determined MTHFR genotype.

Results: The median (range) total folate concentration by LC-MS/MS was higher in the US set [378 (228–820) nmol/L; n = 96] than in the European set [250 (122–582) nmol/L; n = 75]. The whole-blood folate pattern [median (range)] was similar for individuals with C/C (n = 73) and C/T (n = 66) genotype: 88% (71%–91%) and 86% (50%–91%), respectively, for 5-methyltetrahydrofolic acid (5CH3THF) vs 12% (9%–29%) and 14% (9%–51%) for forms other than 5-methyltetrahydrofolic acid (non-5CH3THF). Individuals with T/T (n = 32) genotype had 58% (22%–87%) 5CH3THF vs 42% (13%–78%) non-5CH3THF. Compared with microbiologic assay results, LC-MS/MS (r = 0.94) and BR (r = 0.87) results were significantly lower (−10% and −45%, respectively); however, these differences were concentration dependent and also genotype dependent for the BR assay (−48% for C/C+C/T and −31% for T/T). The microbiologic assay completely recovered [mean (SD)] folates added to a whole blood hemolysate, except for tetrahydrofolic acid (THF) [46.4% (8.1%)]. The BR assay underrecovered 5CH3THF [51% (4.1%)] and 5-formyltetrahydrofolic acid [18% (0.1%)], and overrecovered THF [152% (19%)].

Conclusion: MTHFR C677T polymorphism influences the folate pattern in whole blood. The agreement between total folate by LC-MS/MS and microbiologic assay, independent of the MTHFR genotype, allows the use of one regression equation. Because BR results are genotype dependent, different regression equations should be used.
Inflammation in Atherosclerosis: From Vascular Biology to Biomarker Discovery and Risk Prediction
Authors: Packard René R S , Libby Peter
Published: December 2007

Recent investigations of atherosclerosis have focused on inflammation, providing new insight into mechanisms of disease. Inflammatory cytokines involved in vascular inflammation stimulate the generation of endothelial adhesion molecules, proteases, and other mediators, which may enter the circulation in soluble form. These primary cytokines also induce production of the messenger cytokine interleukin-6, which stimulates the liver to increase production of acute-phase reactants such as C-reactive protein. In addition, platelets and adipose tissue can generate inflammatory mediators relevant to atherothrombosis. Despite the irreplaceable utility of plasma lipid profiles in assessment of atherosclerotic risk, these profiles provide an incomplete picture. Indeed, many cardiovascular events occur in individuals with plasma cholesterol concentrations below the National Cholesterol Education Program thresholds of 200 mg/dL for total cholesterol and 130 mg/dL for low-density lipoprotein (LDL) cholesterol. The concept of the involvement of inflammation in atherosclerosis has spurred the discovery and adoption of inflammatory biomarkers for cardiovascular risk prediction. C-reactive protein is currently the best validated inflammatory biomarker; in addition, soluble CD40 ligand, adiponectin, interleukin 18, and matrix metalloproteinase 9 may provide additional information for cardiovascular risk stratification and prediction. This review retraces the biology of atherothrombosis and the evidence supporting the role of inflammatory biomarkers in predicting primary cardiovascular events in this biologic context.
Task-Related Interaction between Basal Ganglia and Cortical Dopamine Release
Authors: Garraux Gaëtan , Peigneux Philippe , Carson Richard E. , Hallett Mark
Published: December 2007

Dopamine (DA) is a powerful neuromodulator for a wide variety of behaviors. Considerable evidence accumulated from rodent and monkey experiments over the last two decades suggests that DA activity in the frontal cortex is reciprocally linked to that in functionally related basal ganglia (BG) structures. However, the functional importance of this in humans is still unknown. To address this issue, we measured endogenous DA release using positron emission tomography in 15 healthy subjects as they practiced the first training session of a finger sequence learning task. Significant results were observed not only in striatal areas but also in extrastriatal “motor” regions, bilaterally. Faster learning was specifically coupled to lower DA release in the sensorimotor part of the globus pallidus pars interna (GPi) contralateral to the moving hand, which was paralleled by a higher increase in DA levels in the pre-supplementary motor area (pre-SMA). This finding provides original evidence supporting a motor-learning-related interaction between DA release in left GPi and pre-SMA, a mechanism that may also apply to other anatomically and functionally interconnected BG and frontal cortical areas as a function of behavior.
A TAT–DEF–Elk-1 Peptide Regulates the Cytonuclear Trafficking of Elk-1 and Controls Cytoskeleton Dynamics
Authors: Lavaur Jérémie , Bernard Frédéric , Trifilieff Pierre , Pascoli Vincent , Kappes Vincent , Pagès Christiane , Vanhoutte Peter , Caboche Jocelyne
Published: December 2007

The transcription factor Elk-1 plays a key role in cell differentiation, proliferation and apoptosis. This role is thought to arise from its phosphorylation by activated extracellular signal-regulated kinases (ERKs), a critical posttranslational event for the transcriptional activity of the ternary complex composed of Elk-1 and a dimer of serum response factor (SRF) at the serum response element (SRE) regulatory site of transcription. In addition to its nuclear localization, Elk-1 is found in the dendrites and soma of neuronal cells and recent evidence implicate a cytoplasmic proapoptotic function of Elk-1, via its association with the mitochondrial permeability transition pore complex. Thus, the nuclear versus cytoplasmic localization of Elk-1 seems to be crucial for its biological function. In this study we show that the excitatory neurotransmitter, glutamate, induces an ERK-dependent Elk-1 activation and nuclear relocalization. We demonstrate that Elk-1 phosphorylation on Ser383/389 has a dual function and triggers both Elk-1 nuclear translocation and SRE-dependent gene expression. Mutating these sites into inactive residues or using a synthetic penetrating peptide (TAT–DEF–Elk-1), which specifically interferes with the DEF docking domain of Elk-1, prevents Elk-1 nuclear translocation without interfering with ERK nor MSK1 (mitogen- and stress-activated protein kinase 1), a CREB kinase downstream from ERK- activation. This results in a differential regulation of glutamate-induced IEG regulation when compared with classical inhibitors of the ERK pathway. Using the TAT–DEF–Elk-1 peptide or the dominant-negative version of Elk-1, we show that Elk-1 phosphorylation controls dendritic elongation, SRF and Actin expression levels as well as cytoskeleton dynamics.
Inhibiting Glycosaminoglycan Chain Polymerization Decreases the Inhibitory Activity of Astrocyte-Derived Chondroitin Sulfate Proteoglycans
Authors: Laabs Tracy L. , Wang Hang , Katagiri Yasuhiro , McCann Thomas , Fawcett James W. , Geller Herbert M.
Published: December 2007

Chondroitin sulfate proteoglycans (CSPGs) are upregulated in the CNS after injury and participate in the inhibition of axon regeneration mainly through their glycosaminoglycan (GAG) side chains. In the present study, we have identified a new way to alleviate the inhibition of axonal regeneration by CSPG GAGs. We have successfully decreased the amount of CSPG GAG produced by astrocytes by targeting chondroitin polymerizing factor (ChPF), a key enzyme in the CSPG biosynthetic pathway. Using short interfering RNA (siRNA), we reduced ChPF mRNA levels by 70% in both the Neu7 astrocyte cell line and primary rat astrocytes. This reduction leads to a decrease in ChPF protein levels and a reduced amount of CSPG GAG chains in the conditioned media (CM) of these cells. Secretion of neurocan by primary astrocytes and NG2 core protein by Neu7 cells transfected with ChPF siRNA is not decreased, suggesting that inhibiting GAG chain synthesis does not affect core protein trafficking from these cells. CM from siRNA-treated Neu7 cells is a less repulsive substrate for axons than CM from control cells. In addition, axonal outgrowth from cerebellar granule neurons is increased on or in CM from ChPF siRNA-treated Neu7 cells. These data indicate that targeting the biosynthesis of CSPG GAG is a potentially new therapeutic avenue for decreasing CSPG GAG produced by astrocytes after CNS injury.
Dopamine Alters AMPA Receptor Synaptic Expression and Subunit Composition in Dopamine Neurons of the Ventral Tegmental Area Cultured with Prefrontal Cortex Neurons
Authors: Gao Can , Wolf Marina E.
Published: December 2007

Excitatory synapses onto dopamine (DA) neurons of the ventral tegmental area (VTA) represent a critical site of psychostimulant-induced synaptic plasticity. This plasticity involves alterations in synaptic strength through AMPA receptor (AMPAR) redistribution. Here, we report anin vitromodel for studying regulation of AMPAR trafficking in DA neurons under control conditions and after elevation of DA levels, mimicking cocaine exposure. We used cocultures containing rat VTA neurons and prefrontal cortex (PFC) neurons from enhanced cyan fluorescent protein-expressing mice. In VTA-PFC cocultures, D1receptor activation (10 min) increased synaptic and nonsynaptic glutamate receptor subunit 1 (GluR1) and GluR2 surface expression on DA neurons. NMDA or AMPA receptor antagonists blocked this effect, and it was not observed in pure VTA cultures, suggesting that DA agonists acted on D1receptors on PFC neurons, altering their excitatory transmission onto VTA DA neurons and, thus, influencing AMPARs. To mimic the longer elevation in extracellular DA levels produced by systemic cocaine, cocultures were incubated with DA for 1 h. Synaptic GluR1 was increased 24 h later, reminiscent of the increased AMPA/NMDA ratio at excitatory synapses onto VTA DA neurons 24 h after cocaine injection (Ungless et al., 2001). In contrast, GluR2 was unchanged. Analysis of colocalization of surface GluR1–3 labeling suggested that control DA neurons express a substantial number of GluR1/2, GluR2/3, and homomeric GluR1 receptors and that the increase in surface AMPARs 24 h after DA exposure may in part reflect increased GluR1/3-containing receptors. These results help define the cellular basis for plasticity underlying the development of behavioral sensitization.
Selective Deletion ofBdnfin the Ventromedial and Dorsomedial Hypothalamus of Adult Mice Results in Hyperphagic Behavior and Obesity
Authors: Unger Thaddeus J. , Calderon German A. , Bradley Leila C. , Sena-Esteves Miguel , Rios Maribel
Published: December 2007

Brain-derived neurotrophic factor (BDNF) and its receptor TrkB are expressed in several hypothalamic and hindbrain nuclei involved in regulating energy homeostasis, developmentally and in the adult animal. Their depletion during the fetal or early postnatal periods when developmental processes are still ongoing elicits hyperphagic behavior and obesity in mice. Whether BDNF is a chief element in appetite control in the mature brain remains controversial. The required sources of this neurotrophin are also unknown. We show that glucose administration rapidly induced BDNF mRNA expression, mediated byBdnfpromoter 1, and TrkB transcription in the ventromedial hypothalamus (VMH) of adult mice, consistent with a role of this pathway in satiety. Using viral-mediated selective knock-down of BDNF in the VMH and dorsomedial hypothalamus (DMH) of adult mice, we were able to elucidate the physiological relevance of BDNF in energy balance regulation. Site-specific mutants exhibited hyperphagic behavior and obesity but normal energy expenditure. Furthermore, intracerebroventricular administration of BDNF triggered an immediate neuronal response in multiple hypothalamic nuclei in wild-type mice, suggesting that its anorexigenic actions involve short-term mechanisms. Locomotor, aggressive, and depressive-like behaviors, all of which are associated with neural circuits involving the VMH, were not altered in VMH/DMH-specific BDNF mutants. These findings demonstrate that BDNF is an integral component of central mechanisms mediating satiety in the adult mouse and, moreover, that its synthesis in the VMH and/or DMH is required for the suppression of appetite.
Omega-3 Fatty Acid Docosahexaenoic Acid Increases SorLA/LR11, a Sorting Protein with Reduced Expression in Sporadic Alzheimer's Disease (AD): Relevance to AD Prevention
Authors: Ma Qiu-Lan , Teter Bruce , Ubeda Oliver J. , Morihara Takashi , Dhoot Dilsher , Nyby Michael D. , Tuck Michael L. , Frautschy Sally A. , Cole Greg M.
Published: December 2007

Environmental and genetic factors, notably ApoE4, contribute to the etiology of late-onset Alzheimer's disease (LOAD). Reduced mRNA and protein for an apolipoprotein E (ApoE) receptor family member, SorLA (LR11) has been found in LOAD but not early-onset AD, suggesting that LR11 loss is not secondary to pathology. LR11 is a neuronal sorting protein that reduces amyloid precursor protein (APP) trafficking to secretases that generate β-amyloid (Aβ). Genetic polymorphisms that reduce LR11 expression are associated with increased AD risk. However these polymorphisms account for only a fraction of cases with LR11 deficits, suggesting involvement of environmental factors. Because lipoprotein receptors are typically lipid-regulated, we postulated that LR11 is regulated by docosahexaenoic acid (DHA), an essential ω-3 fatty acid related to reduced AD risk and reduced Aβ accumulation. In this study, we report that DHA significantly increases LR11 in multiple systems, including primary rat neurons, aged non-Tg mice and an aged DHA-depleted APPsw AD mouse model. DHA also increased LR11 in a human neuronal line.In vivoelevation of LR11 was also observed with dietary fish oil in young rats with insulin resistance, a model for type II diabetes, another AD risk factor. These data argue that DHA induction of LR11 does not require DHA-depleting diets and is not age dependent. Because reduced LR11 is known to increase Aβ production and may be a significant genetic cause of LOAD, our results indicate that DHA increases in SorLA/LR11 levels may play an important role in preventing LOAD.
Asymmetry of Anticipatory Activity in Visual Cortex Predicts the Locus of Attention and Perception
Authors: Sylvester Chad M. , Shulman Gordon L. , Jack Anthony I. , Corbetta Maurizio
Published: December 2007

Humans can use advance information to direct spatial attention before stimulus presentation and respond more accurately to stimuli at the attended location compared with unattended locations. Likewise, spatially directed attention is associated with anticipatory activity in the portion of visual cortex representing the attended location. It is unknown, however, whether and how anticipatory signals predict the locus of spatial attention and perception. Here, we show that prestimulus, preparatory activity is highly correlated across regions representing attended and unattended locations. Comparing activity representing attended versus unattended locations, rather than measuring activity for only one location, dramatically improves the accuracy with which preparatory signals predict the locus of attention, largely by removing this positive correlation common across locations. In V3A, moreover, only the difference in activity between attended and unattended locations predicts whether upcoming visual stimuli will be accurately perceived. These results suggest that the locus of attention is coded in visual cortex by an asymmetry of anticipatory activity between attended and unattended locations and that this asymmetry predicts the accuracy of perception. This coding strategy may bias activity in downstream brain regions to represent the stimulus at the attended location.
Selective Targeting of Different Neural Cell Adhesion Molecule Isoforms during Motoneuron–Myotube Synapse Formation in Culture and the Switch from an Immature to Mature Form of Synaptic Vesicle Cycling
Authors: Hata Katsusuke , Polo-Parada Luis , Landmesser Lynn T.
Published: December 2007

Characterization of neuromuscular junction formation and function in mice lacking all neural cell adhesion molecule (NCAM) isoforms or only the 180 isoform demonstrated that the 180 isoform was required at adult synapses to maintain effective transmission with repetitive stimulation whereas the 140 and/or 120 isoform(s) were sufficient to mediate the downregulation of synaptic vesicle cycling along the axon after synapse formation. However, the expression and targeting of each isoform and its relationship to distinct forms of synaptic vesicle cycling before and after synapse formation was previously unknown. By transfecting chick motoneurons with fluorescently tagged mouse 180, 140 and 120 isoforms, we show that before myotube contact the 180 and 140 isoforms are expressed in distinct puncta along the axon which are sites of an immature form (Brefeldin A sensitive, L-type Ca2+channel mediated) of vesicle cycling. After myotube contact the 140 and 180 isoforms are downregulated from the axon and selectively targeted to the presynaptic terminal. This coincided with the downregulation of vesicle cycling along the axon and the expression of the mature form (BFA insensitive, P/Q type Ca2+channel mediated) of vesicle cycling at the terminal. The synaptic targeting of exogenously expressed 180 and 140 isoforms also occurred when chick motoneurons contacted +/+ mouse myotubes; however only the 180 but not the 140 isoform was targeted on contact with NCAM−/−myotubes. These observations indicate that postsynaptic NCAM is required for the synaptic targeting of presynaptic 140 NCAM but that the localization of presynaptic 180 NCAM occurs via a different mechanism.
Systemic and Nasal Delivery of Orexin-A (Hypocretin-1) Reduces the Effects of Sleep Deprivation on Cognitive Performance in Nonhuman Primates
Authors: Deadwyler Sam A. , Porrino Linda , Siegel Jerome M. , Hampson Robert E.
Published: December 2007

Hypocretin-1 (orexin-A) was administered to sleep-deprived (30–36 h) rhesus monkeys immediately preceding testing on a multi-image delayed match-to-sample (DMS) short-term memory task. The DMS task used multiple delays and stimulus images and effectively measures cognitive defects produced by sleep deprivation (Porrino et al., 2005). Two methods of administration of orexin-A were tested, intravenous injections (2.5–10.0 μg/kg, i.v.) and a novel method developed for nasal delivery via an atomizer spray mist to the nostrils (dose estimated 1.0 μg/kg). Results showed that orexin-A delivered via the intravenous and nasal routes significantly improved performance in sleep-deprived monkeys; however, the nasal delivery method was significantly more effective than the highest dose (10 μg/kg) of intravenous orexin-A tested. The improvement in performance by orexin-A was specific to trials classified as high versus low cognitive load as determined by performance difficulty under normal testing conditions. Except for the maximum intravenous dose (10 μg/kg), neither delivery method affected task performance in alert non-sleep-deprived animals. The improved performance in sleep-deprived animals was accompanied by orexin-A related alterations in local cerebral glucose metabolism (CMRglc) in specific brain regions shown previously to be engaged by the task and impaired by sleep deprivation (Porrino et al., 2005). Consistent with the differential effects on performance, nasal delivered orexin-A produced a more pronounced reversal of sleep deprivation induced changes in brain metabolic activity (CMRglc) than intravenous orexin-A. These findings provide strong evidence for the effectiveness of intranasal orexin-A in alleviating cognitive deficits produced by loss of sleep.
Impaired Migration in the Rostral Migratory Stream But Spared Olfactory Function after the Elimination of Programmed Cell Death in Bax Knock-Out Mice
Authors: Kim Woon Ryoung , Kim Younghwa , Eun Bokkee , Park Ok-hee , Kim Hyun , Kim Kyungjin , Park Chang-Hwan , Vinsant Sharon , Oppenheim Ronald W. , Sun Woong
Published: December 2007

Rats and mice exhibit neurogenesis of olfactory bulb (OB) interneurons throughout adulthood. To homeostatically maintain stable neuron numbers, it is necessary to continuously remove a subset of OB neurons by programmed cell death (PCD). Here we demonstrate that Bax is critical for the elimination of OB neurons by showing that Bax-KO mice exhibit greatly reduced PCD in the OB. Despite the reduction of PCD, however, proliferation of progenitors and the size of the OB were virtually unaffected in Bax-knock-out (KO) mice. However, reducing PCD by Bax deletion affected the migration of a subset of adult-produced neurons by the disruption of glial tube formation as well as by premature detachment of neuroblasts from the migratory chain. Rescued cells aberrantly remained in the subventricular zone (SVZ)-rostral migratory stream (RMS), in which they differentiated into calretinin+or GABA-expressing interneurons. Because of the migratory deficit, OB cell homeostasis involving new cell entry and PCD (neuronal turnover) was virtually absent in adult Bax-KO mice. Despite this, Bax-KO mice exhibited normal olfactory behaviors such as odor discrimination and olfactory memory which are thought to be influenced by adult neurogenesis. These results demonstrate that PCD is involved in the regulation of RMS migration and differentiation after OB neurogenesis, but that animals maintain normal olfactory function in the absence of PCD.
Using Imagination to Understand the Neural Basis of Episodic Memory
Authors: Hassabis Demis , Kumaran Dharshan , Maguire Eleanor A.
Published: December 2007

Functional MRI (fMRI) studies investigating the neural basis of episodic memory recall, and the related task of thinking about plausible personal future events, have revealed a consistent network of associated brain regions. Surprisingly little, however, is understood about the contributions individual brain areas make to the overall recollective experience. To examine this, we used a novel fMRI paradigm in which subjects had to imagine fictitious experiences. In contrast to future thinking, this results in experiences that are not explicitly temporal in nature or as reliant on self-processing. By using previously imagined fictitious experiences as a comparison for episodic memories, we identified the neural basis of a key process engaged in common, namely scene construction, involving the generation, maintenance and visualization of complex spatial contexts. This was associated with activations in a distributed network, including hippocampus, parahippocampal gyrus, and retrosplenial cortex. Importantly, we disambiguated these common effects from episodic memory-specific responses in anterior medial prefrontal cortex, posterior cingulate cortex and precuneus. These latter regions may support self-schema and familiarity processes, and contribute to the brain's ability to distinguish real from imaginary memories. We conclude that scene construction constitutes a common process underlying episodic memory and imagination of fictitious experiences, and suggest it may partially account for the similar brain networks implicated in navigation, episodic future thinking, and the default mode. We suggest that additional brain regions are co-opted into this core network in a task-specific manner to support functions such as episodic memory that may have additional requirements.
Analyzing Somatosensory Axon Projections with the Sensory Neuron-SpecificAdvillinGene
Authors: Hasegawa Hiroshi , Abbott Sara , Han Bao-Xia , Qi Yi , Wang Fan
Published: December 2007

Peripheral sensory neurons detect diverse physical stimuli and transmit the information into the CNS. At present, the genetic tools for specifically studying the development, plasticity, and regeneration of the sensory axon projections are limited. We found that the gene encoding Advillin, an actin binding protein that belongs to the gelsolin superfamily, is expressed almost exclusively in peripheral sensory neurons. We next generated a line of knock-in mice in which the start codon of theAdvillinis replaced by the gene encoding human placenta alkaline phosphatase (Avil-hPLAP mice). In heterozygous Avil-hPLAP mice, sensory axons, the exquisite sensory endings, as well as the fine central axonal collaterals can be clearly visualized with a simple alkaline phosphatase staining. Using this mouse line, we found that the development of peripheral target innervation and sensory ending formation is an ordered process with specific timing depending on sensory modalities. This is also true for the in-growth of central axonal collaterals into the brainstem and the spinal cord. Our results demonstrate that Avil-hPLAP mouse is a valuable tool for specifically studying peripheral sensory neurons. Functionally, we found that the regenerative axon growth ofAdvillin-null sensory neurons is significantly shortened and that deletion ofAdvillinreduces the plasticity of whisker-related barrelettes patterns in the hindbrain.
Radiofrequency Heating of the Cornea: An Engineering Review of Electrodes and Applicators
Authors: Berjano Enrique J , Navarro Enrique , Ribera Vicente , Gorris Javier , Alió Jorge L
Published: December 2007

This paper reviews the different applicators and electrodes employed to create localized heating in the cornea by means of the application of radiofrequency (RF) currents. Thermokeratoplasty (TKP) is probably the best known of these techniques and is based on the principle that heating corneal tissue (particularly the central part of the corneal tissue, i.e. the central stroma) causes collagen to shrink, and hence changes the corneal curvature. Firstly, we point out that TKP techniques are a complex challenge from the engineering point of view, due to the fact that it is necessary to create very localized heating in a precise location (central stroma), within a narrow temperature range (from 58 to 76ºC). Secondly, we describe the different applicator designs (i.e. RF electrodes) proposed and tested to date. This review is planned from a technical point of view, i.e. the technical developments are classified and described taking into consideration technical criteria, such as energy delivery mode (monopolar versus bipolar), thermal conditions (dry versus cooled electrodes), lesion pattern (focal versus circular lesions), and application placement (surface versus intrastromal).