Landmark detection for fusion of fundus and MRI toward a patient-specific multimodal eye model.

Ophthalmologists typically acquire different image modalities to diagnose eye pathologies. They comprise, e.g., Fundus photography, optical coherence tomography, computed tomography, and magnetic resonance imaging (MRI). Yet, these images are often complementary and do express the same pathologies in a different way. Some pathologies are only visible in a particular modality. Thus, it is beneficial for the ophthalmologist to have these modalities fused into a single patient-specific model. The goal of this paper is a fusion of Fundus photography with segmented MRI volumes. This adds information to MRI that was not visible before like vessels and the macula. This paper contributions include automatic detection of the optic disc, the fovea, the optic axis, and an automatic segmentation of the vitreous humor of the eye.

Use of an empty, Plasmapore-covered titanium cage for interbody fusion after anterior cervical microdiscectomy.

The use of cages of different material and shapes for cervical discectomy with fusion (ACDF) has increased during the last few years. The use of additional osteogenic material is controversial. We prospectively evaluated an empty, Plasmapore-covered titanium cage (PCTC) in 45 patients undergoing 58 ACDFs. Patients were evaluated using standard clinical and radiological criteria. Good to excellent outcome was achieved in 93%, 78% and 75% after 3, 12 and 48 months, respectively. Sixty-five percent of patients could resume their prior work after 48 months. Disc space height and lordosis could be preserved in all cases. Two percent of the treated levels showed subsidence and 2% increased segmental motion. There were no procedure-related complications. Implantation of an empty PCTC after microsurgical anterior cervical discectomy is a safe procedure with good results and low incidence of complications. Disc height and lordosis can be preserved with low incidence of subsidence and good fusion rates.

Secondary Accident Data Fusion for Assessing Long-Term Performance of Transportation Systems, 2007

Secondary accident statistics can be useful for studying the impact of traffic incident management strategies. An easy-to-implement methodology is presented for classifying secondary accidents using data fusion of a police accident database with intranet incident reports. A current method for classifying secondary accidents uses a static threshold that represents the spatial and temporal region of influence of the primary accident, such as two miles and one hour. An accident is considered secondary if it occurs upstream from the primary accident and is within the duration and queue of the primary accident. However, using the static threshold may result in both false positives and negatives because accident queues are constantly varying. The methodology presented in this report seeks to improve upon this existing method by making the threshold dynamic. An incident progression curve is used to mark the end of the queue throughout the entire incident. Four steps in the development of incident progression curves are described. Step one is the processing of intranet incident reports. Step two is the filling in of incomplete incident reports. Step three is the nonlinear regression of incident progression curves. Step four is the merging of individual incident progression curves into one master curve. To illustrate this methodology, 5,514 accidents from Missouri freeways were analyzed. The results show that secondary accidents identified by dynamic versus static thresholds can differ by more than 30%.

Fusion of data sets in multivariate linear regression with errors-in-variables

We consider the application of normal theory methods to the estimation and testing of a general type of multivariate regressionmodels with errors--in--variables, in the case where various data setsare merged into a single analysis and the observable variables deviatepossibly from normality. The various samples to be merged can differ on the set of observable variables available. We show that there is a convenient way to parameterize the model so that, despite the possiblenon--normality of the data, normal--theory methods yield correct inferencesfor the parameters of interest and for the goodness--of--fit test. Thetheory described encompasses both the functional and structural modelcases, and can be implemented using standard software for structuralequations models, such as LISREL, EQS, LISCOMP, among others. An illustration with Monte Carlo data is presented.

The SM protein Vps33 and the t-SNARE H(abc) domain promote fusion pore opening.

Intracellular membrane fusion proceeds via distinct stages of membrane docking, hemifusion and fusion pore opening and depends on interacting families of Rab, SNARE and SM proteins. Trans-SNARE complexes dock the membranes in close apposition. Efficient fusion requires further SNARE-associated proteins. They might increase the number of trans-SNARE complexes or the fusogenic potential of a single SNARE complex. We investigated the contributions of the SM protein Vps33 to hemifusion and pore opening between yeast vacuoles. Mutations in Vps33 that weaken its interactions with the SNARE complex allowed normal trans-SNARE pairing and lipid mixing but retarded content mixing. Deleting the H(abc) domain of the vacuolar t-SNARE Vam3, which interacts with Vps33, had the same effect. This suggests that SM proteins promote fusion pore opening by enhancing the fusogenic activity of a SNARE complex. They should thus be considered integral parts of the fusion machinery.

Pretargeted radioimmunotherapy using genetically engineered antibody-streptavidin fusion proteins for treatment of non-hodgkin lymphoma.

Purpose: Pretargeted radioimmunotherapy (PRIT) using streptavidin (SAv)-biotin technology can deliver higher therapeutic doses of radioactivity to tumors than conventional RIT. However, "endogenous" biotin can interfere with the effectiveness of this approach by blocking binding of radiolabeled biotin to SAv. We engineered a series of SAv FPs that downmodulate the affinity of SAv for biotin, while retaining high avidity for divalent DOTA-bis-biotin to circumvent this problem.Experimental Design: The single-chain variable region gene of the murine 1F5 anti-CD20 antibody was fused to the wild-type (WT) SAv gene and to mutant SAv genes, Y43A-SAv and S45A-SAv. FPs were expressed, purified, and compared in studies using athymic mice bearing Ramos lymphoma xenografts.Results: Biodistribution studies showed delivery of more radioactivity to tumors of mice pretargeted with mutant SAv FPs followed by (111)In-DOTA-bis-biotin [6.2 +/- 1.7% of the injected dose per gram (%ID/gm) of tumor 24 hours after Y43A-SAv FP and 5.6 +/- 2.2%ID/g with S45A-SAv FP] than in mice on normal diets pretargeted with WT-SAv FP (2.5 +/- 1.6%ID/g; P = 0.01). These superior biodistributions translated into superior antitumor efficacy in mice treated with mutant FPs and (90)Y-DOTA-bis-biotin [tumor volumes after 11 days: 237 +/- 66 mm(3) with Y43A-SAv, 543 +/- 320 mm(3) with S45A-SAv, 1129 +/- 322 mm(3) with WT-SAv, and 1435 +/- 212 mm(3) with control FP (P < 0.0001)].Conclusions: Genetically engineered mutant-SAv FPs and bis-biotin reagents provide an attractive alternative to current SAv-biotin PRIT methods in settings where endogenous biotin levels are high. Clin Cancer Res; 17(23); 7373-82. (C)2011 AACR.

Model-based Segmentation and Fusion of 3D Computed Tomography and 3D Ultrasound of the Eye for Radiotherapy Planning

Computed Tomography (CT) represents the standard imaging modality for tumor volume delineation for radiotherapy treatment planning of retinoblastoma despite some inherent limitations. CT scan is very useful in providing information on physical density for dose calculation and morphological volumetric information but presents a low sensitivity in assessing the tumor viability. On the other hand, 3D ultrasound (US) allows a highly accurate definition of the tumor volume thanks to its high spatial resolution but it is not currently integrated in the treatment planning but used only for diagnosis and follow-up. Our ultimate goal is an automatic segmentation of gross tumor volume (GTV) in the 3D US, the segmentation of the organs at risk (OAR) in the CT and the registration of both modalities. In this paper, we present some preliminary results in this direction. We present 3D active contour-based segmentation of the eye ball and the lens in CT images; the presented approach incorporates the prior knowledge of the anatomy by using a 3D geometrical eye model. The automated segmentation results are validated by comparing with manual segmentations. Then, we present two approaches for the fusion of 3D CT and US images: (i) landmark-based transformation, and (ii) object-based transformation that makes use of eye ball contour information on CT and US images.

Multiresolution-based image fusion with additive wavelet decomposition

The standard data fusion methods may not be satisfactory to merge a high-resolution panchromatic image and a low-resolution multispectral image because they can distort the spectral characteristics of the multispectral data. The authors developed a technique, based on multiresolution wavelet decomposition, for the merging and data fusion of such images. The method presented consists of adding the wavelet coefficients of the high-resolution image to the multispectral (low-resolution) data. They have studied several possibilities concluding that the method which produces the best results consists in adding the high order coefficients of the wavelet transform of the panchromatic image to the intensity component (defined as L=(R+G+B)/3) of the multispectral image. The method is, thus, an improvement on standard intensity-hue-saturation (IHS or LHS) mergers. They used the ¿a trous¿ algorithm which allows the use of a dyadic wavelet to merge nondyadic data in a simple and efficient scheme. They used the method to merge SPOT and LANDSATTM images. The technique presented is clearly better than the IHS and LHS mergers in preserving both spectral and spatial information.

Introduction of sensor spectral response into image fusion methods. Application to wavelet-based methods

Usual image fusion methods inject features from a high spatial resolution panchromatic sensor into every low spatial resolution multispectral band trying to preserve spectral signatures and improve spatial resolution to that of the panchromatic sensor. The objective is to obtain the image that would be observed by a sensor with the same spectral response (i.e., spectral sensitivity and quantum efficiency) as the multispectral sensors and the spatial resolution of the panchromatic sensor. But in these methods, features from electromagnetic spectrum regions not covered by multispectral sensors are injected into them, and physical spectral responses of the sensors are not considered during this process. This produces some undesirable effects, such as resolution overinjection images and slightly modified spectral signatures in some features. The authors present a technique which takes into account the physical electromagnetic spectrum responses of sensors during the fusion process, which produces images closer to the image obtained by the ideal sensor than those obtained by usual wavelet-based image fusion methods. This technique is used to define a new wavelet-based image fusion method.

Report on a special investigation of the Region 4 Fusion Office in Atlantic, Iowa for the period March 1, 2006 through August 31, 2009

Report on a special investigation of the Region 4 Fusion Office in Atlantic, Iowa for the period March 1, 2006 through August 31, 2009

Etude des effets du monoxyde d'azote (NO) sur le métabolisme des acides gras libres à partir d'un modèle de souris invalidée pour le gène de la NO synthase endothéliale

RESUME GENERAL Au cours de ces dernières années, le monoxyde d'azote (NO) produit par une famille d'enzymes, les NO synthases (NOS), est apparu comme un effecteur central dans la régulation du système cardiovasculaire et du métabolisme énergétique. Chez l'homme, un défaut de production du NO est associé à des maladies cardiovasculaires et métaboliques comme la résistance à l'insuline ou le diabète de type 2. Ces pathologies se retrouvent chez les souris invalidées pour la NO synthase endothéliale (eN0S-/-) qui présentent non seulement une hypertension mais également une résistance à l'insuline et une dyslipidémie (augmentation des triglycérides et des acides gras libres). Ces anomalies sont étroitement associées et impliquées dans le développement du diabète de type 2. Dans cette étude, nous avons essayé de déterminer à partir du modèle de souris eN0S-/-, l'influence de la eNOS et de son produit, le NO, sur la régulation du métabolisme lipidique intracellulaire. Ainsi, nous avons montré que cette enzyme et le NO régulent directement l'activité β-oxydative des mitochondries isolées du muscle squelettique, du muscle cardiaque et du tissu adipeux blanc. Par ailleurs, dans le muscle de ces souris, le contenu des mitochondries et l'expression des gènes impliqués dans leur biogénèse sont diminués, ce qui suggère que la eNOS et/ou le NO contrôlent également la synthèse de ces organelles. Les mitochondries, via la β-oxydation, sont impliquées dans la production d'énergie à partir des acides gras libres. Dans notre modèle animal, la diminution de la β-oxydation dans le muscle, s'accompagne d'une accumulation des triglycérides intramyocellulaires. Cette accumulation prédispose fortement au développement de la résistance à l'insuline. Les anomalies du métabolisme β-oxydatif favorisent donc probablement l'apparition de la dyslipidémie et le développement de la résistance à l'insuline observées chez les souris eN0S-/-. Cette hypothèse est soutenue par différentes études effectuées chez l'homme et l'animal qui suggèrent qu'une dysfonction mitochondriale peut être à l'origine de la résistance à l'insuline. Ces données récentes et les résultats de ce travail apportent un regard nouveau sur le rôle du NO dans le développement des maladies métaboliques que sont la résistance à l'insuline, le diabète de type 2 et l'obésité. Elles placent aux centres de ces mécanismes une organelle, la mitochondrie, située au carrefour des métabolismes glucidiques et lipidiques. SUMMARY Over the last years, nitric oxide (NO), synthesized by a family of enzymes, the NO synthases, has become a central regulator of the cardiovascular system and energy metabolism. In humans, defective NO production is found in cardiovascular and metabolic diseases such as insulin resistance or type 2 diabetes mellitus. These alterations are also found in knockout mice for the endothelial nitric oxide synthase (eN0S-/-), which are not only hypertensive but also display insulin resistance and dyslipidemia (with increased triglyceride and free fatty acid levels). These pathologic features are tightly linked and involved in the pathogenesis of type 2 DM. In this study, using eN0S-/- mice, we determined the role played by this enzyme and its product, NO, on intracellular lipid metabolism. We show that eNOS and NO directly regulate β-oxidation in mitochondria isolated from skeletal and cardiac muscle as well as white adipose tissue. Furthermore, in the skeletal muscle of these mice, the mitochondrial content and the expression of genes involved in mitochondrial biogenesis are decreased, suggesting that eNOS and/or NO also regulate the synthesis of this intracellular organelle. Mitochondria, through β-oxidation, play a role in energy production from free fatty acids. In our animal model, decreased β-oxidation in skeletal muscle is associated with accumulation of intramyocellular lipids. This increased lipid content plays an important role in the pathogenesis of insulin resistance. Defective β-oxidation, therefore, probably favours the development of insulin resistance and dyslipidemia as seen in these animals. This hypothesis is strengthened by studies in humans and animals indicating that mitochondrial dysfunction is associated with insulin resistance. These recent data and the results of this work provide evidence for a role of NO in the development of metabolic diseases such as insulin resistance or type diabetes mellitus. They put as a central player, an organelle, the mitochondria, which lies at the crossway of carbohydrate and lipid metabolism. RESUME DIDACTIQUE Le maintien des fonctions vitales et l'accomplissement d'une activité physique nécessitent, chez l'homme, un apport quotidien d'énergie. Cette énergie est présente, dans l'alimentation, principalement sous forme de graisses (lipides) ou de sucres. La production d'énergie s'effectue en majorité dans le muscle au niveau d'une organelle particulière, la mitochondrie. La régulation du métabolisme énergétique fait intervenir de nombreux facteurs de régulation dont l'un des plus connu est l'insuline. De nombreuses maladies comme le diabète de type 2, l'obésité ou le syndrome métabolique découlent de la dérégulation du métabolisme énergétique. Un mécanisme particulier, la résistance à l'insuline, qui se caractérise par un défaut d'action de l'insuline au niveau de ses tissus cibles (foie, muscle...) est souvent impliqué dans le développement de ces pathologies. L'étude de ces anomalies métaboliques nécessite l'utilisation de modèles, notamment animaux, qui ont la particularité de reproduire partiellement un état pathologique caractéristique de certaines maladies humaines. Dans ce travail, nous avons utilisé un modèle de souris dont la particularité est de ne pas exprimer une enzyme, la monoxyde d'azote (NO) synthase endothéliale (eNOS), responsable de la synthèse d'un gaz, le NO. Ces souris présentent une hypertension artérielle, des anomalies du métabolisme des lipides et une résistance à l'insuline. Or, de récents travaux effectués chez l'homme montrent que des individus insulino-résistants ou diabétiques de type 2 ont une diminution de la production de NO. Lors de nos investigations, nous avons démontré que la quantité et la capacité des mitochondries à utiliser les lipides comme substrat énergétique est diminuée dans les muscles des souris eN0S-/-. Par ailleurs, ces deux anomalies sont associées dans ce tissu à une accumulation des lipides. De façon très intéressante, ce phénomène est décrit dans de nombreuses études effectuées chez l'homme et l'animal comme favorisant le développement de la résistance à l'insuline. Les résultats de ce travail suggèrent donc que la eNOS et/ou le NO joue un rôle important dans l'activité et la synthèse des mitochondries. Le NO pourrait donc constituer une cible thérapeutique dans le traitement des maladies métaboliques.

Sequence analysis and expression of the attachment and fusion proteins of canine distemper virus wild-type strain A75/17.

The biological properties of wild-type A75/17 and cell culture-adapted Onderstepoort canine distemper virus differ markedly. To learn more about the molecular basis for these differences, we have isolated and sequenced the protein-coding regions of the attachment and fusion proteins of wild-type canine distemper virus strain A75/17. In the attachment protein, a total of 57 amino acid differences were observed between the Onderstepoort strain and strain A75/17, and these were distributed evenly over the entire protein. Interestingly, the attachment protein of strain A75/17 contained an extension of three amino acids at the C terminus. Expression studies showed that the attachment protein of strain A75/17 had a higher apparent molecular mass than the attachment protein of the Onderstepoort strain, in both the presence and absence of tunicamycin. In the fusion protein, 60 amino acid differences were observed between the two strains, of which 44 were clustered in the much smaller F2 portion of the molecule. Significantly, the AUG that has been proposed as a translation initiation codon in the Onderstepoort strain is an AUA codon in strain A75/17. Detailed mutation analyses showed that both the first and second AUGs of strain A75/17 are the major translation initiation sites of the fusion protein. Similar analyses demonstrated that, also in the Onderstepoort strain, the first two AUGs are the translation initiation codons which contribute most to the generation of precursor molecules yielding the mature form of the fusion protein.