Configuration Sharing Optimized Placement and Routing

Reconfigurable systems have been shown to achieve very high computational performance. However, the overhead associated with reconfiguration of hardware remains a critical factor in overall system performance. This paper discusses the development and evaluation of a technique to minimize the delay associated with reconfiguration based upon optimized sharing of configuration bit streams between design contexts. This is achieved through modified placement and routing algorithms

Organization and connectivity of premotor interneurons in the mouse spinal cord

Movement is the final behavioral output of neuronal activity in the spinal cord. In all vertebrates, motor neurons are grouped into motor neuron pools, the functional units innervating individual muscles. Spinal interneurons receive a variety of inputs from the brain, cerebellum and sensory afferents, process this information and as the final outcome, the information reaches the motor neurons that control the activation of the innervated muscles. For generation of movement, precise activation of distinct motor neuron pools at the right moment in time is crucial and this precision is possible due to the cohorts of spinal interneurons, connected with specificity to distinct motor neuron pools that regulate motor neuronal activity. How premotor circuits connect to distinct motor neuron pools with specificity is poorly understood and represented a main question of my PhD thesis work. In my thesis, I present the results of my studies on connectivity of premotor interneuron populations to specific motor neuron pools in two layers - as general distribution patterns specific to control the regulation of particular muscles and by closer examination of the connection specificity of one class of the spinal pre-motor interneurons, the cholinergic partition cells. One significant part of this project was to develop a tool that allowed studying the pre-motor interneurons innervating defined motor neuron pools. For this purpose, I have adapted a novel rabies virus based tool (Wickersham et al. (2007b)) for mono- transsynaptic tracing of neuronal circuits in the spinal cord in vivo. I was successful in establishing an anatomical rabies-virus based connectivity assay in early postnatal mice in order to study the connectivity scheme of premotor neurons, the neuronal cohorts monosynaptically connected to motor neurons. The main parts of my thesis focus on: 1) motor neuron pools connectivity with premotor interneurons that appear to be widely-distributed when analysed at the segmental level, yet group into stereotypic populations, and differing for pools innervating functionally-distinct muscles; 2) local or segmental distribution of interneurons depending on their molecular identity; 3) specificity of the connectivity of cholinergic partition cells involved in the regulation of motor neuron excitability - this subpopulation of premotor interneurons segregate into ipsilaterally and bilaterally projecting populations, the latter exhibiting preferential connections to equivalent motor neuron pools bilaterally. A minor part of my thesis is devoted to the connectivity of the spinal pre-motor interneurons in α2-chimaerin mutant mice. Data presented in this part are preliminary and this project needs continuation, but the results begin to provide insight into the function of the α2-chimaerin molecule in the axon guidance and perhaps connectivity process of the bilaterally projecting subclass of partition cells and a dorsal subgroup of premotor interneurons. I demonstrate that the distribution of cholinergic partition cells connected to a particular motor neuron pool is different in α2-chimaerin mutant mice than in the wild-type mice. I also show that the distribution pattern of ectopic bilaterally projecting premotor interneurons in α2-chimaerin mutant mice what concerns the dorsal population of premotor interneurons. These studies of premotor interneurons visualize the widespread but precise nature of connectivity with motor neuron pools, reveal exquisite synaptic specificity for bilaterally projecting cholinergic partition cells and show the importance of the α2-chimaerin molecule in axon guidance and connectivity processes for the establishment of the appropriate premotor circuits in the spinal cord

Using Spectral-Domain Optical Coherence Tomography to Follow Outer Retinal Structure Changes in a Patient with Recurrent Punctate Inner Choroidopathy

Punctate inner choroidopathy (PIC) is a rare idiopathic inflammatory disorder of the retina and choroid usually affecting healthy, young, myopic females and presenting with photopsia, paracentral scotomata, and blurred vision. It is characterized by yellow-white chorioretinal lesions concentrated in the posterior pole, no vitritis, relapsing inflammatory activity of the retina and choroid, and frequent development of choroidal neovascular membranes. Here we describe a case in which spectral-domain optical coherence tomography (SD-OCT) imaging was used to monitor outer retinal structure changes associated with recurrent PIC over time. SD-OCT, which is both quantative and objective, provides an efficient, non-invasive way to follow recurrent inflammatory chorioretinal lesion activity, choroidal neovascular membrane development, and treatment response in patients with recurrent PIC

Subclinical Photoreceptor Disruption in Response to Severe Head Trauma

Commotio retinae is a transient opacification of the retina due to outer retinal disruption occurring in a contrecoup fashion after blunt trauma.Histological studies in animals and humans after ocular blunt trauma have revealed that disruption occurs at the level of the photoreceptor outer segments and retinal pigment epithelium.Recent reports using optical coherence tomography (OCT) have shown detectable disruption at the level of the photoreceptor inner segment/outer segment junction and retinal pigment epithelium and that these changes may be reversible over time with restoration of normal outer retinal architecture.However, the resolution of existing OCT technology may not be sensitive enough to detect photoreceptor disruption. Adaptive optics (AO) imaging systems enable cellular-resolution imaging of the human retina, and there is a growing number of cases where deficits have been visible on AO images but not on OCT. Herein, we report a case of subclinical photoreceptor disruption after head trauma as seen by an AO scanning ophthalmoscope (AOSO) but not apparent clinically or on spectral-domain OCT (SD-OCT)

Outer Retinal Structure in Best Vitelliform Macular Dystrophy

Importance Demonstrating the utility of adaptive optics scanning light ophthalmoscopy (AOSLO) to assess outer retinal structure in Best vitelliform macular dystrophy (BVMD). Objective To characterize outer retinal structure in BVMD using spectral-domain optical coherence tomography (SD-OCT) and AOSLO. Design, Setting, and Participants Prospective, observational case series. Four symptomatic members of a family with BVMD with known BEST1 mutation were recruited at the Advanced Ocular Imaging Program research lab at the Medical College of Wisconsin Eye Institute, Milwaukee. Intervention Thickness of 2 outer retinal layers corresponding to photoreceptor inner and outer segments was measured using SD-OCT. Photoreceptor mosaic AOSLO images within and around visible lesions were obtained, and cone density was assessed in 2 subjects. Main Outcome and Measure Photoreceptor structure. Results Each subject was at a different stage of BVMD, with photoreceptor disruption evident by AOSLO at all stages. When comparing SD-OCT and AOSLO images from the same location, AOSLO images allowed for direct assessment of photoreceptor structure. A variable degree of retained photoreceptors was seen within all lesions. The photoreceptor mosaic immediately adjacent to visible lesions appeared contiguous and was of normal density. Fine hyperreflective structures were visualized by AOSLO, and their anatomical orientation and size were consistent with Henle fibers. Conclusions and Relevance The AOSLO findings indicate that substantial photoreceptor structure persists within active lesions, accounting for good visual acuity in these patients. Despite previous reports of diffuse photoreceptor outer segment abnormalities in BVMD, our data reveal normal photoreceptor structure in areas adjacent to clinical lesions. This study demonstrates the utility of AOSLO for understanding the spectrum of cellular changes that occur in inherited degenerations such as BVMD. Photoreceptors are often significantly affected at various stages of inherited degenerations, and these changes may not be readily apparent with current clinical imaging instrumentation

Microscopic Inner Retinal Hyper-reflective Phenotypes in Retinal and Neurologic Disease

Purpose. We surveyed inner retinal microscopic features in retinal and neurologic disease using a reflectance confocal adaptive optics scanning light ophthalmoscope (AOSLO). Methods. Inner retinal images from 101 subjects affected by one of 38 retinal or neurologic conditions and 11 subjects with no known eye disease were examined for the presence of hyper-reflective features other than vasculature, retinal nerve fiber layer, and foveal pit reflex. The hyper-reflective features in the AOSLO images were grouped based on size, location, and subjective texture. Clinical imaging, including optical coherence tomography (OCT), scanning laser ophthalmoscopy, and fundus photography was analyzed for comparison. Results. Seven categories of hyper-reflective inner retinal structures were identified, namely punctate reflectivity, nummular (disc-shaped) reflectivity, granular membrane, waxy membrane, vessel-associated membrane, microcysts, and striate reflectivity. Punctate and nummular reflectivity also was found commonly in normal volunteers, but the features in the remaining five categories were found only in subjects with retinal or neurologic disease. Some of the features were found to change substantially between follow up imaging months apart. Conclusions. Confocal reflectance AOSLO imaging revealed a diverse spectrum of normal and pathologic hyper-reflective inner and epiretinal features, some of which were previously unreported. Notably, these features were not disease-specific, suggesting that they might correspond to common mechanisms of degeneration or repair in pathologic states. Although prospective studies with larger and better characterized populations, along with imaging of more extensive retinal areas are needed, the hyper-reflective structures reported here could be used as disease biomarkers, provided their specificity is studied further

Photoreceptor Inner Segment Morphology in Best Vitelliform Macular Dystrophy

PURPOSE To characterize outer retina structure in best vitelliform macular dystrophy (BVMD) and to determine the effect of macular lesions on overlying and adjacent photoreceptors. METHODS Five individuals with BVMD were followed prospectively with spectral domain optical coherence tomography and confocal and nonconfocal split-detector adaptive optics scanning light ophthalmoscopy (AOSLO). The AOSLO cone photoreceptor mosaic images were obtained within and around retinal lesions. Cone density was measured inside and outside lesions. In 2 subjects, densities were compared with published measurements acquired ∼2.5 years before. One subject was imaged 3 times over a 5-month period. RESULTS The AOSLO imaging demonstrated that photoreceptor morphology within BVMD retinal lesions was highly variable depending on the disease stage, with photoreceptor structure present even in advanced disease. The AOSLO imaging was repeatable even in severe disease over short-time and long-time intervals. Photoreceptor density was normal in retinal areas immediately adjacent to lesions and stable over ∼2.5 years. Mobile disk-like structures possibly representing subretinal macrophages were also observed. CONCLUSION Combined confocal and nonconfocal split-detector AOSLO imaging reveals substantial variability within clinical lesions in all stages of BVMD. Longitudinal cellular photoreceptor imaging could prove a powerful tool for understanding disease progression and monitoring emerging therapeutic treatment response in inherited degenerations such as BVMD

Localisation of the human hSuv3p helicase in the mitochondrial matrix and its preferential unwinding of dsDNA

We characterised the human hSuv3p protein belonging to the family of NTPases/helicases. In yeast mitochondria the hSUV3 orthologue is a component of the degradosome complex and participates in mtRNA turnover and processing, while in Caenorhabditis elegans the hSUV3 orthologue is necessary for viability of early embryos. Using immunofluorescence analysis, an in vitro mitochondrial uptake assay and sub‐fractionation of human mitochondria we show hSuv3p to be a soluble protein localised in the mitochondrial matrix. We expressed and purified recombinant hSuv3p protein from a bacterial expression system. The purified enzyme was capable of hydrolysing ATP with a Km of 41.9 µM and the activity was only modestly stimulated by polynucleotides. hSuv3p unwound partly hybridised dsRNA and dsDNA structures with a very strong preference for the latter. The presented analysis of the hSuv3p NTPase/helicase suggests that new functions of the protein have been acquired in the course of evolution

Shrinking binary and planetary orbits by Kozai cycles with tidal friction

At least two arguments suggest that the orbits of a large fraction of binary stars and extrasolar planets shrank by 1-2 orders of magnitude after formation: (i) the physical radius of a star shrinks by a large factor from birth to the main sequence, yet many main-sequence stars have companions orbiting only a few stellar radii away, and (ii) in current theories of planet formation, the region within ~0.1 AU of a protostar is too hot and rarefied for a Jupiter-mass planet to form, yet many "hot Jupiters" are observed at such distances. We investigate orbital shrinkage by the combined effects of secular perturbations from a distant companion star (Kozai oscillations) and tidal friction. We integrate the relevant equations of motion to predict the distribution of orbital elements produced by this process. Binary stars with orbital periods of 0.1 to 10 days, with a median of ~2 d, are produced from binaries with much longer periods (10 d to 10^5 d), consistent with observations indicating that most or all short-period binaries have distant companions (tertiaries). We also make two new testable predictions: (1) For periods between 3 and 10 d, the distribution of the mutual inclination between the inner binary and the tertiary orbit should peak strongly near 40 deg and 140 deg. (2) Extrasolar planets whose host stars have a distant binary companion may also undergo this process, in which case the orbit of the resulting hot Jupiter will typically be misaligned with the equator of its host star.Comment: Submitted to ApJ; 18 pages, 10 figure

Multimodal Imaging of Photoreceptor Structure in Choroideremia

Purpose Choroideremia is a progressive X-linked recessive dystrophy, characterized by degeneration of the retinal pigment epithelium (RPE), choroid, choriocapillaris, and photoreceptors. We examined photoreceptor structure in a series of subjects with choroideremia with particular attention to areas bordering atrophic lesions. Methods Twelve males with clinically-diagnosed choroideremia and confirmed hemizygous mutations in the CHM gene were examined. High-resolution images of the retina were obtained using spectral domain optical coherence tomography (SD-OCT) and both confocal and non-confocal split-detector adaptive optics scanning light ophthalmoscope (AOSLO) techniques. Results Eleven CHM gene mutations (3 novel) were identified; three subjects had the same mutation and one subject had two mutations. SD-OCT findings included interdigitation zone (IZ) attenuation or loss in 10/12 subjects, often in areas with intact ellipsoid zones; RPE thinning in all subjects; interlaminar bridges in the imaged areas of 10/12 subjects; and outer retinal tubulations (ORTs) in 10/12 subjects. Only split-detector AOSLO could reliably resolve cones near lesion borders, and such cones were abnormally heterogeneous in morphology, diameter and density. On split-detector imaging, the cone mosaic terminated sharply at lesion borders in 5/5 cases examined. Split-detector imaging detected remnant cone inner segments within ORTs, which were generally contiguous with a central patch of preserved retina. Conclusions Early IZ dropout and RPE thinning on SD-OCT are consistent with previously published results. Evidence of remnant cone inner segments within ORTs and the continuity of the ORTs with preserved retina suggests that these may represent an intermediate state of retinal degeneration prior to complete atrophy. Taken together, these results supports a model of choroideremia in which the RPE degenerates before photoreceptors