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Introduction/Objectifs La degenerescence synaptique est un evenement pathogene central dans la maladie d’Alzheimer (MA) qui survient tot au cours de la maladie et qui est en correlation avec les symptomes cognitifs. Les proteines synaptiques semblent cruciales a la fois pour la transmission synaptique et la fonction cognitive. L’evaluation des proteines synaptiques dans le liquide cephalo-spinal (LCS) pourrait refleter un dysfonctionnement synaptique et etre en correlation avec le declin cognitif de la MA. Materiels/Patients et methodes Dans une cohorte retrospective monocentrique, GAP43, Neurogranine, SNAP25 total, SNAP 25aa40 et synaptotgamine ont ete evalues dans le LCS. Ces biomarqueurs ont ete doses soit par ELISA ou par spectrometrie de masse. Nous avons compare leur pouvoir discriminatoire a l’aide de l’analyse des courbes ROC et utilise un modele de regression logistique par paliers retrogrades pour selectionner les biomarqueurs utiles pour discriminer la MA des patients non atteints de la MA. Resultats Cette etude a inclus 241 patients (âge moyen 71 ± 9 ans) : les biomarqueurs etudies etaient significativement plus eleves chez les patients MCI-MA et MA compares aux temoins neurologiques, les patients avec MCI non du a MA et les autres maladies neurodegeneratives. GAP-43 et SNAP-25 avaient le pouvoir superieur de discriminer lla MA (aire sous courbe ROC = 0,92 et 0,93 respectivement). Dans les modeles de selection par etapes retrogrades, GAP_43 et SNAP-25 etaient tous deux des predicteurs de la MA. Conclusions Les biomarqueurs synaptiques du LCS sont des biomarqueurs prometteurs pour surveiller la perte synaptique dans la MA, y compris a un stade tres precoce. Ces biomarqueurs devraient etre egalement utiles pour explorer la physiopathologie directement chez les patients atteints de la MA.

Introduction La maladie d’Alzheimer (MA) est une maladie neurodegenerative caracterisee par l’accumulation de peptide Aβ et de proteine tau hyperphosphorylee. Ces accumulations entrainent de facon precoce une atteinte puis une perte synaptique. L’atteinte synaptique semble etre le substrat anatomique de l’atteinte cognitive. A ce jour, le lien entre plusieurs marqueurs synaptiques mesures, les fonctions cognitives et les lesions IRM n’a pas ete explore dans de larges cohortes. Methodes Dans une cohorte retrospective, monocentrique bien caracterisee nous avons mesure plusieurs marqueurs synaptiques dans le liquide cerebrospinal (LCS). Nous avons ensuite etudie les liens entre differentes fonctions cognitives, ces marqueurs synaptiques et des lesions observees a l’IRM encephalique. Resultats Deux cent quarante et un patients ont ete inclus (âge moyen 71 ± 9 ans) : 79 MA, 31 trouble cognitif leger (TCL) du a une MA, 48 TCL non du a une MA, 48 autres demences et 35 controles neurologiques. Les biomarqueurs synaptiques etaient correles entre eux, avec le taux de proteine tau mais pas avec le taux d’Aβ. Tous les marqueurs synaptiques etaient significativement correles avec les performances dans plusieurs fonctions cognitives. Par ailleurs, nous n’avons observe aucune correlation entre les lesions IRM et les resultats des biomarqueurs synaptiques. Conclusions A travers l’analyse de proteines synaptiques dans le LCS et leur lien avec certaines fonctions cognitives, nos resultats refletent l’atteinte topographique cerebrale.

Dans la maladie d’Alzheimer (MA), la neurodegenerescence se traduit par des atteintes synaptiques et neuroaxonales qui precoces mais dont les relations chronologiques et physiopathologiques demeurent incertaines. Les taux de neurofilaments - chaine legere (NFL) dans le liquide cerebrospinal (LCS) et, plus recemment, dans le plasma refletent l’atteinte neuroaxonale dans plusieurs pathologies neurologiques. A ce jour, les proteines synaptiques ne sont mesurables que dans le LCS. Jusqu’a present, le lien entre les taux de proteines synaptiques dans le LCS, le taux de NFL plasmatiques, les fonctions cognitives et les anomalies de l’IRM cerebrale n’a pas ete etudie. Dans une cohorte retrospective monocentrique, les taux de plusieurs biomarqueurs synaptiques dans le LCS et de NFL plasmatique ont ete mesures. En utilisant des modeles de regression logistique et multivaries, nous avons etudie les relations entre ces marqueurs, les tests neuropsychologiques et les anomalies IRM. Nous avons egalement etudie les liens entre les biomarqueurs de la maladie d’Alzheimer dans le LCS, les taux de NFL et ceux des marqueurs synaptiques. Deux cent quarante et un patients ont ete inclus. Les NFL plasmatiques etaient significativement plus eleves chez les patients presentant des lesions MA comparativement aux autres groupes de patients. Aucune correlation n’etait notee entre les taux de NFL et les marqueurs synaptiques et/ou les marqueurs usuels de la MA dans le LCS. Cependant, les taux de biomarqueurs synaptiques et de NFL etaient tous deux correles a plusieurs fonctions cognitives, notamment la memoire visuelle et les praxies. De plus, les taux de NFL, mais pas ceux des marqueurs synaptiques, etaient correles aux anomalies IRM, notamment les lesions lacunaires et de la substance blanche. Dans cette cohorte, les biomarqueurs des lesions synaptiques et axonales ne sont pas correles entre eux et semblent refleter des evenements pathologiques differents. Cependant, ces biomarqueurs apparaissent associes a des alterations de processus neurocognitifs communs, revelant de possibles dommages contigus dans des reseaux cerebraux associes.

Stroke induces extensive tissue remodeling, resulting in the activation of several cell types in the brain as well as recruitment of blood-borne leucocytes. Radixin is part of a cytoskeleton linker protein family with the ability to connect transmembrane proteins to the actin cytoskeleton, promoting cell functions involving a dynamic cytoskeleton such as morphological changes, cell division and migration which are common events of different cell types after stroke. In the healthy adult brain radixin is expressed in Olig2(+) cells throughout the brain and in neural progenitor cells in the subventricular zone. In the current study, we detected a 2.5 fold increase in the number of radixin positive cells in the peri-infarct cortex two weeks after the induction of cortical stroke by photothrombosis. Similarly, the number of Olig2(+) cells increased in the peri-infarct area after stroke; however, the number of radixin(+)/Olig2(+) cells was unchanged. Neural progenitor cells maintained radixin expression on their route to the infarct. More surprising however, was the expression of radixin in activated microglia in the peri-infarct cortex. Seventy percent of Iba1(+) cells expressed radixin after stroke, a population which was not present in the control brain. Furthermore, activation of radixin was predominantly detected in the peri-infarct region of oligodendrocyte progenitors and microglia. The specific location of radixin(+) cells in the peri-infarct region and in microglia suggests a role for radixin in microglial activation after stroke.

The objectives of this study were to identify useful predictive factors for tree species identification of individual trees and to compare classifications based on a combination of LiDAR data and multi-spectral images with classification by the use of each individual data source. Crown segments derived from LiDAR data were mapped to multi-spectral images for extraction of spectral data within individual tree crowns. Several features, related to height distribution of laser returns in the canopy, canopy shape, proportion of different types of laser returns, and intensity of laser returns, were derived from LiDAR data. Data from a test site in southern Sweden were used (lat. 58°30' N, long. 13°40' E). The forest consisted of Norway spruce (Picea abies), Scots pine (Pinus sylvestris), and deciduous trees. Classification into these three tree species groups was validated for 1711 trees that had been detected in LiDAR data within 14 field plots (sizes of 20×50 m2 or 80×80 m2). The LiDAR data were acquired by the TopEye MkII system (50 LiDAR measurements per m2) and the multi-spectral images were taken by the Zeiss/Intergraph Digital Mapping Camera. The overall classification accuracy was 96% when both data sources were combined.

Purpose: Adult hippocampal neurogenesis is enhanced in several models for temporal lobe epilepsy (TLE). In this study, we used low-dose whole brain radiation to suppress hippocampal neurogenesis and then studied the effect of this treatment on epileptogenesis in a kindling model for TLE. Methods: Half of the rats were exposed to a radiation dose of 8 Gy one day before the initiation of a rapid kindling protocol. Afterdischarge threshold (ADT), afterdischarge duration (ADD), clinical seizure severity, and inflammation were compared between groups. On the first and third day after radiation, rats were injected with 5'-bromo-2'-deoxyuridine (BrdU) to evaluate neurogenesis. Seven and 21 days after radiation, numbers of doublecortin (DCX) positive neuroblasts in subgranular zone and granule cell layer were compared between groups. Results: We showed that radiation significantly suppressed neurogenesis and neuroblast production during kindling acquisition. Radiation prevented an increase in ADT that became significantly lower in radiated rats. On the third and fourth kindling acquisition day radiated rats developed more severe seizures more rapidly, which resulted in a significantly higher mean severity score on these days. Differences in ADD could not be demonstrated. Discussion: Our results demonstrate that brain radiation with a relatively low dose effectively suppressed the generation of new granule cells and transiently enhanced excitability during kindling acquisition. Although seizure-induced neurogenesis was lower in the radiated rats we could not detect a strong effect on the final establishment of the permanent fully kindled state, which argues against a prominent role of seizure-induced neurogenesis in epileptogenesis.

This article reviews the research and application of airborne laser scanning for forest inventory in Finland, Norway and Sweden. The first experiments with scanning lasers for forest inventory were conducted in 1991 using the FLASH system, a full-waveform experimental laser developed by the Swedish Defence Research Institute. In Finland at the same time, the HUTSCAT profiling radar provided experiences that inspired the following laser scanning research. Since 1995, data from commercially operated time-of-flight scanning lasers (e.g. TopEye, Optech ALTM and TopoSys) have been used. Especially in Norway, the main objective has been to develop methods that are directly suited for practical forest inventory at the stand level. Mean tree height, stand volume and basal area have been the most important forest mensurational parameters of interest. Laser data have been related to field training plot measurements using regression techniques, and these relationships have been used to predict corresponding properti...

Individual trees can be detected using high-density airborne laser scanner data. Also, variables characterizing the detected trees such as tree height, crown area, and crown base height can be measured. The Scandinavian boreal forest mainly consists of Norway spruce ( Picea abies L. Karst.), Scots pine ( Pinus sylvestris L.), and deciduous trees. It is possible to separate coniferous from deciduous trees using near-infrared images, but pine and spruce give similar spectral signals. Airborne laser scanning, measuring structure and shape of tree crowns could be used for discriminating between spruce and pine. The aim of this study was to test classification of Scots pine versus Norway spruce on an individual tree level using features extracted from airborne laser scanning data. Field measurements were used for training and validation of the classification. The position of all trees on 12 rectangular plots (50×20 m 2 ) were measured in field and tree species was recorded. The dominating species (>80%) was Norway spruce for six of the plots and Scots pine for six plots. The field-measured trees were automatically linked to the laser-measured trees. The laser-detected trees on each plot were classified into species classes using all laser-detected trees on the other plots as training data. The portion correctly classified trees on all plots was 95%. Crown base height estimations of individual trees were also evaluated ( r =0.84). The classification results in this study demonstrate the ability to discriminate between pine and spruce using laser data. This method could be applied in an operational context. In the first step, a segmentation of individual tree crowns is performed using laser data. In the second step, tree species classification is performed based on the segments. Methods could be developed in the future that combine laser data with digital near-infrared photographs for classification with the three classes: Norway spruce, Scots pine, and deciduous trees.

Acta Obstet Gynecol Scand 2003; 82: 10–17. © Acta Obstet Gynecol Scand 2003 Background. The aim of this clinical evaluation was to study birth experience, post-traumatic stress symptoms, and satisfaction with care in new mothers who had consulted specially trained midwives because of a fear of childbirth during pregnancy. Methods. Sixty-two women were eligible for the study, of whom 53 (85%) participated at 1–14 months postpartum. For comparison, a group of 53 women were matched for parity and mode of delivery. All 106 women completed two self-rating scales, the Wijma Delivery Experience Questionnaire (W-DEQ) and the Impact of Event Scale (IES), and answered several open questions about their opinion of the antenatal preparation given. Results. Those women who had been treated for fear of childbirth reported a rather more frightening experience of delivery, and more frequent symptoms of post-traumatic stress related to delivery than did the women in the comparison group. Nevertheless, satisfaction with care was manifest in the study group. Conclusions. Women who seek help for fear of childbirth are a vulnerable group. Because the counseling received by the women in this study did not accord them the same positive experience of childbirth as the average parturient at the unit, more effective forms of treatment may be necessary. However, as most of the women were very satisfied with their care and with the outcome, one may assume that the care given had improved their situation to some degree.

Neuronal progenitors capable of long distance migration are produced throughout life in the subventricular zone (SVZ). Migration from the SVZ is carried out along a well-defined pathway called the rostral migratory stream (RMS). Our recent finding of the specific expression of the cytoskeleton linker protein radixin in neuroblasts suggests a functional role for radixin in RMS migration. The ezrin-radixin-moesin (ERM) family of proteins is capable of regulating migration through interaction with the actin cytoskeleton and transmembrane proteins. The ERM proteins are differentially expressed in the RMS with radixin and moesin localized to neuroblasts, and ezrin expression confined to astrocytes of the glial tubes. Here, we inhibited radixin function using the quinocarmycin analog DX52-1 which resulted in reduced neuroblast migration in vitro, while glial migration remained unaltered. Furthermore, the morphology of neuroblasts was distorted resulting in a rounded shape with no or short polysialylated neural cell adhesion molecule positive processes. Intracerebroventricular infusion of the radixin inhibitor resulted in accumulation of neuroblasts in the anterior SVZ. Neuroblast chains were short and intermittently interrupted in the SVZ and considerably disorganized in the RMS. Moreover, we studied the proliferation activity in the RMS after radixin inhibition, since concentrated radixin expression has been demonstrated in the cleavage furrow of dividing cells, which indicates a role of radixin in cell division. Radixin inhibition decreased neuroblast proliferation, whereas the proliferation of other cells in the RMS was not affected. Our results demonstrate a significant role for radixin in neuroblast proliferation and migration.

Summary Purpose Levetiracetam (LEV) is a broad-spectrum antiepileptic drug (AED) with possibly also antiepileptogenic properties. LEV has a specific binding site in the central nervous system and reduces brain excitability; however, the precise mechanism of action (MOA) of LEV remains unclear. To further unravel the potential MOA pathways of LEV we investigated altered protein expression and cell proliferation in rat hippocampal tissue during LEV administration. Methods On day 1 of the experiment, rats were randomly assigned to a treatment group (LEV, 600mg/kg/day, n =10) and a control group (saline, n =10). On days 2 and 3 rats were injected with bromodeoxyuridine (50mg/kg, i.p., BID). After 7 days of treatment rats were killed and their brains removed. The right hemisphere was processed for histochemistry. The left hippocampus was dissected and frozen for proteomic analysis. Proteins were extracted from the tissue and two-dimensional gel electrophoresis was performed. Results Treatment with LEV did not influence hippocampal cell proliferation. Multivariate analysis of differential protein expression, determined by proteomic analysis, revealed a significant clustering of control and treatment groups. The proteins which most contribute to the difference between groups were identified with mass spectrometry. The identified proteins were either involved in cytoskeleton, energy metabolism, neurotransmission, signal transduction, myelinization or stress response. Discussion LEV does not affect hippocampal cell proliferation but has significant effects on the expression of proteins involved in a variety of physiological processes involved in physiological processes that play an important role in the currently identified MOAs of AEDs such as neurotransmission and signal transduction.

A series of peptidomimetics intended to promote the beta-hairpin motif have been studied. Structural variations include a turn region with and without a photoswitchable chromophore, and strands with amino acid side chains supporting various degrees of interstrand interactions for hairpin stabilisation. The propensity of the compounds to form beta-hairpins was evaluated experimentally by NMR spectroscopy, translational self-diffusion studies and CD spectroscopy. In the presence of hairpin stabilising interstrand interactions, the structurally flexible stilbene chromophore appeared to be well compatible with the imposed secondary structure.

One of the more exciting capabilities foreseen for future 3-D imaging laser radars is to see through vegetation and camouflage nettings. We have used ground based and airborne scanning laser radars to collect data of various types of terrain and vegetation. On some occasions reference targets were used to collect data on reflectivity and to evaluate penetration. The data contains reflectivity and range distributions and were collected at 1.5 and 1.06 μm wavelength with range accuracies in the 1-10 cm range. The seasonal variations for different types of vegetation have been studied. A preliminary evaluation of part of the data set was recently presented at another SPIE conference. Since then the data have been analyzed in more detail with emphasis on testing algorithms and future system performance by simulation of different sensors and scenarios. Evaluation methods will be discussed and some examples of data sets will be presented.

The ongoing technical developments on airborne laser scanner systems, with shorter pulses, increased operation altitudes, focal plane array detectors, full-waveform digitization and recoding, etc. provide new opportunities for the expansion and growth of military as well as civilian applications. However, for the continuing development of systems and applications one crucial issue is the research and development of new and efficient laser data processing methods for analysis and visualization. In this paper we will present some recent developments on visualization and analysis of full-waveform data. We will discuss visualization of waveform data by inserting the waveform samples in a 3D volume consisting of small 3D cells referred to as voxels. We will also present an approach for extracting additional 3D point data from the waveforms. The long term goal of this research is to develop methods for automated extraction of natural as well as man-made objects. The aim is to support the construction of high-fidelity 3D virtual environment models and detection and identification of man-made objects.

This paper will describe measurements of snow reflection using laser radar. There seems to be a rather limited number of publications on snow reflection related to laser radar, which is why we decided to investigate a little more details of snow reflection including that from different kinds of snow as well as the angular reflection properties. We will discuss reflectance information obtained by two commercial scanning laser radars using the wavelengths 0.9 μm and 1.5 μm. Data will mainly be presented at the eye safe wavelength 1.5 μm but some measurements were also performed for the wavelength 0.9 μm. We have measured snow reflection during a part of a winter season which gave us opportunities to investigate different types of snow and different meteorological conditions. The reflection values tend to decrease during the first couple of hours after a snowfall. The snow structure seems to be more important for the reflection than the snow age. In general the snow reflection at 1.5 μm is rather low and the reflectivity values can vary between 0.5 and 10 % for oblique incidence depending on snow structure which in turn depends on age, air temperature, humidity etc. The snow reflectivity at the 0.9 μm laser wavelength is much higher, more than 50 % for fresh snow. Images of snow covered scenes will be shown together with reflection data including BRDFs.© (2005) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Exciting development is taking place in 3 D sensing laser radars. Scanning systems are well established for mapping from airborne and ground sensors. 3 D sensing focal plane arrays (FPAs) enable a full range and intensity image can be captured in one laser shot. Gated viewing systems also produces 3 D target information. Many applications for 3 D laser radars are found in robotics, rapid terrain visualization, augmented vision, reconnaissance and target recognition, weapon guidance including aim point selection and others. The net centric warfare will demand high resolution geo-data for a common description of the environment. At FOI we have a measurement program to collect data relevant for 3 D laser radars using airborne and tripod mounted equipment for data collection. Data collection spans from single pixel waveform collection (1 D) over 2 D using range gated imaging to full 3 D imaging using scanning systems. This paper will describe 3 D laser data from different campaigns with emphasis on range distribution and reflections properties for targets and background during different seasonal conditions. Example of the use of the data for system modeling, performance prediction and algorithm development will be given. Different metrics to characterize the data set will also be discussed.

Over the years imaging laser radar systems have been developed for both military and civilian (topographic) applications. Among the applications, 3D data is used for environment modeling and object reconstruction and recognition. The data processing methods are mainly developed separately for military or topographic applications, seldom both application areas are in mind. In this paper, an overview of methods from both areas is presented. First, some of the work on ground surface estimation and classification of natural objects, for example trees, is described. Once natural objects have been detected and classified, we review some of the extensive work on reconstruction and recognition of man-made objects. Primarily we address the reconstruction of buildings and recognition of vehicles. Further, some methods for evaluation of measurement systems and algorithms are described. Models of some types of laser radar systems are reviewed, based on both physical and statistical approaches, for analysis and evaluation of measurement systems and algorithms. The combination of methods for reconstruction of natural and man-made objects is also discussed. By combining methods originating from civilian and military applications, we believe that the tools to analyze a whole scene become available. In this paper we show examples where methods from both application fields are used to analyze a scene.

Detailed 3D environment models for visualization and computer based analyses are important in many defence and homeland security applications, e.g. crisis management, mission planning and rehearsal, damage assessment, etc. The high resolution data from airborne laser radar systems for 3D sensing provide an excellent source of data for obtaining the information needed for many of these models. To utilise the 3D data provided by the laser radar systems however, efficient methods for data processing and environment model construction needs to be developed. In this paper we will present some results on the development of laser data processing methods, including methods for data classification, bare earth extraction, 3D-reconstruction of buildings, and identification of single trees and estimation of their position, height, canopy size and species. We will also show how the results can be used for the construction of detailed 3D environment models for military modelling and simulation applications. The methods use data from discrete return airborne laser radar systems and digital cameras.

The aim of this clinical evaluation was to study birth experience, post-traumatic stress symptoms, and satisfaction with care in new mothers who had consulted specially trained midwives because of a fear of childbirth during pregnancy.Sixty-two women were eligible for the study, of whom 53 (85%) participated at 1-14 months postpartum. For comparison, a group of 53 women were matched for parity and mode of delivery. All 106 women completed two self-rating scales, the Wijma Delivery Experience Questionnaire (W-DEQ) and the Impact of Event Scale (IES), and answered several open questions about their opinion of the antenatal preparation given.Those women who had been treated for fear of childbirth reported a rather more frightening experience of delivery, and more frequent symptoms of post-traumatic stress related to delivery than did the women in the comparison group. Nevertheless, satisfaction with care was manifest in the study group.Women who seek help for fear of childbirth are a vulnerable group. Because the counseling received by the women in this study did not accord them the same positive experience of childbirth as the average parturient at the unit, more effective forms of treatment may be necessary. However, as most of the women were very satisfied with their care and with the outcome, one may assume that the care given had improved their situation to some degree.

The relative binding affinities to human dihydrofolate reductase of four new potential antifolates, containing ester linkages between the two aromatic systems, were estimated by free energy perturbation simulations. The ester analogue, predicted to exhibit the highest binding affinity to human dihydrofolate reductase, and a reference ester (more structurally related to methotrexate) were synthesized. As deduced from the measured IC(50) values, the calculated ranking of the ligands was correct although a greater difference in affinity was indicated by the experimental measurements. Among the new antifolates the most potent inhibitor exhibited a similar pharmacokinetic profile to methotrexate but lacked activity in a complex antiarthritic model in rat in vivo.

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