Automated Segmentation of Hippocampal Subfields From Ultra-High Resolution In Vivo MRI

Recent developments in MRI data acquisition technology are starting to yield images that show anatomical features of the hippocampal formation at an unprecedented level of detail, providing the basis for hippocampal subfield measurement. However, a fundamental bottleneck in MRI studies of the hippocampus at the subfield level is that they currently depend on manual segmentation, a laborious process that severely limits the amount of data that can be analyzed. In this article, we present a computational method for segmenting the hippocampal subfields in ultra-high resolution MRI data in a fully automated fashion. Using Bayesian inference, we use a statistical model of image formation around the hippocampal area to obtain automated segmentations. We validate the proposed technique by comparing its segmentations to corresponding manual delineations in ultra-high resolution MRI scans of 10 individuals, and show that automated volume measurements of the larger subfields correlate well with manual volume estimates. Unlike manual segmentations, our automated technique is fully reproducible, and fast enough to enable routine analysis of the hippocampal subfields in large imaging studies.National Institutes of Health (U.S.) (NIH NCRR; Grant number: P41-RR14075)National Institutes of Health (U.S.) (Grant R01 RR16594-01A1)National Institutes of Health (U.S.) (Grant NAC P41-RR13218)Biomedical Informatics Research Network (BIRN002)Biomedical Informatics Research Network (U24 RR021382)National Institute of Biomedical Imaging and Bioengineering (U.S.) (R01 EB001550)National Institute of Biomedical Imaging and Bioengineering (U.S.) (R01EB006758)National Institute of Biomedical Imaging and Bioengineering (U.S.) (NAMIC U54-EB005149)National Institute of Neurological Disorders and Stroke (U.S.) (R01 NS052585-01)National Institute of Neurological Disorders and Stroke (U.S.) (R01 NS051826)Mental Illness and Neuroscience Discovery (MIND) InstituteEllison Medical Foundation (Autism & Dyslexia Project

Motor recovery and cortical reorganization after constraint-induced movement therapy in stroke patients: a preliminary study.

Constraint-induced movement therapy (CIMT) is a physical rehabilitation regime that has been previously shown to improve motor function in chronic hemiparetic stroke patients. However, the neural mechanisms supporting rehabilitation-induced motor recovery are poorly understood. The goal of this study was to assess motor cortical reorganization after CIMT using functional magnetic resonance imaging (fMRI). In a repeated-measures design, 4 incompletely recovered chronic stroke patients treated with CIMT underwent motor function testing and fMRI. Five age-matched normal subjects were also imaged. A laterality index (LI) was determined from the fMRI data, reflecting the distribution of activation in motor cortices contralateral compared with ipsilateral to the moving hand. Pre-intervention fMRI showed a lower LI during affected hand movement of stroke patients (LI = 0.23+/-0.07) compared to controls (LI unaffected patient hand = 0.65+/-0.10; LI dominant normal hand = 0.65+/-0.11; LI nondominant normal hand = 0.69+/-0.11; P < 0.05) due to trends toward increased ipsilateral motor cortical activation. Motor function testing showed that patients made significant gains in functional use of the stroke-affected upper extremity (detected by the Motor Activity Log) and significant reductions in motor impairment (detected by the Fugl-Meyer Stroke Scale and the Wolf Motor Function Test) immediately after CIMT, and these effects persisted at 6-month follow-up. The behavioral effects of CIMT were associated with a trend toward a reduced LI from pre-intervention to immediately post-intervention (LI = -0.01+/-0.06, P = 0.077) and 6 months post-intervention (LI = -0.03+/-0.15). Stroke-affected hand movement was not accompanied by mirror movements during fMRI, and electromyographic measures of mirror recruitment under simulated fMRI conditions were not correlated with LI values. These data provide preliminary evidence that gains in motor function produced by CIMT in chronic stroke patients may be associated with a shift in laterality of motor cortical activation toward the undamaged hemisphere

Perturbing HIV-1 Ribosomal Frameshifting Frequency Reveals a cis Preference for Gag-Pol Incorporation into Assembling Virions

HIV-1 virion production is driven by Gag and Gag-Pol (GP) proteins, with Gag forming the bulk of the capsid and driving budding, while GP binds Gag to deliver the essential virion enzymes protease, reverse transcriptase, and integrase. Virion GP levels are traditionally thought to reflect the relative abundances of GP and Gag in cells (;1:20), dictated by the frequency of a 21 programmed ribosomal frameshifting (PRF) event occurring in gag-pol mRNAs. Here, we exploited a panel of PRF mutant viruses to show that mechanisms in addition to PRF regulate GP incorporation into virions. First, we show that GP is enriched ;3-fold in virions relative to cells, with viral infectivity being better maintained at subphysiological levels of GP than when GP levels are too high. Second, we report that GP is more efficiently incorporated into virions when Gag and GP are synthesized in cis (i.e., from the same gag-pol mRNA) than in trans, suggesting that Gag/GP translation and assembly are spatially coupled processes. Third, we show that, surprisingly, virions exhibit a strong upper limit to trans-delivered GP incorporation; an adaptation that appears to allow the virus to temper defects to GP/Gag cleavage that may negatively impact reverse transcription. Taking these results together, we propose a "weighted Goldilocks"scenario for HIV-1 GP incorporation, wherein combined mechanisms of GP enrichment and exclusion buffer virion infectivity over a broad range of local GP concentrations. These results provide new insights into the HIV-1 virion assembly pathway relevant to the anticipated efficacy of PRF-targeted antiviral strategies.National Institutes of Health R01AI110221, P01CA022332, R35GM118131, T32GM00834

Investigating the effectiveness of many-core network processors for high performance cyber protection systems. Part I, FY2011.

This report documents our first year efforts to address the use of many-core processors for high performance cyber protection. As the demands grow for higher bandwidth (beyond 1 Gbits/sec) on network connections, the need to provide faster and more efficient solution to cyber security grows. Fortunately, in recent years, the development of many-core network processors have seen increased interest. Prior working experiences with many-core processors have led us to investigate its effectiveness for cyber protection tools, with particular emphasis on high performance firewalls. Although advanced algorithms for smarter cyber protection of high-speed network traffic are being developed, these advanced analysis techniques require significantly more computational capabilities than static techniques. Moreover, many locations where cyber protections are deployed have limited power, space and cooling resources. This makes the use of traditionally large computing systems impractical for the front-end systems that process large network streams; hence, the drive for this study which could potentially yield a highly reconfigurable and rapidly scalable solution

Linkages among runoff, dissolved organic carbon, and the stable oxygen isotope composition of seawater and other water mass indicators in the Arctic Ocean

Author Posting. © American Geophysical Union, 2005. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 110 (2005): G02013, doi:10.1029/2005JG000031.Concentrations of dissolved organic carbon (DOC) and δ18O values have been determined following sampling of runoff from a number of major arctic rivers, including the Ob, Yenisey, Lena, Kolyma, Mackenzie and Yukon in 2003-2004. These data are considered in conjunction with marine data for DOC, δ18O values, nutrients, salinity, and fluorometric indicators of DOC that were obtained as part of the Shelf-Basin Interactions program at the continental shelf-basin boundary of the Chukchi and Beaufort Seas. These marine data indicate that the freshwater component is most likely derived from regional sources, such as the Mackenzie, the Bering Strait inflow and possibly eastern Siberian rivers, including the Kolyma, or the Lena but not rivers further west in the Eurasian arctic. Contributions of freshwater from melted sea ice to marine surface waters appeared to be insignificant over annual cycles compared to runoff, although on a seasonal basis, freshwater from melted sea ice was locally dominant following a major sea-ice retreat into the Canada Basin in 2002. DOC concentrations were correlated with the runoff fraction, with an apparent meteoric water DOC concentration of 174 ± 1 μM (standard error). This concentration is lower than the flow-weighted concentrations measured at river mouths of the five largest Arctic rivers (358 to 917 μM), indicating that removal of terrigenous DOC during transport through estuaries, shelves and in the deep basin. DOC data indicate that flow-weighted concentrations in the two largest North American arctic rivers, the Yukon (625μM) and the Mackenzie (382 μM), are lower than in the three largest Eurasian arctic rivers, the Ob (825 μM), the Yenesey (858 μM) and the Lena (917 μM). A fluorometric indicator of chromophoric dissolved organic matter (CDOM) that has provided estimates of terrigenous DOC concentrations in the Eurasian Arctic was not correlated with DOC concentrations in the Amerasian marine waters studied, except below the upper Arctic Ocean halocline. Nutrient distributions and concentrations as well as derived nutrient ratios suggest the CDOM fluorometer may be responding to the release of chromophoric materials from continental shelf sediments. Shipboard incubation experiments with undisturbed sediment cores indicate that continental shelf sediments on the Bering and Chukchi Sea shelves are likely to be a net source of DOC to the Arctic Ocean.The PARTNERS and SBI projects have been supported by the Office of Polar Programs of the U.S. National Science Foundation

Simulation and novice nurses: A review

Objective To identify the existing simulation session and the impact of simulation on novice nurse. Method The articles were searched through CINAHL, Scopus, Proquest, and OVID online database. Articles published from 2000, in English and among novice nurses were selected for review. Then, a narrative review was conducted guided by what are the existing simulation session been used and the impact on novice nurse. Result Total of 19 articles been selected for review out of 272 articles. The findings of the reviewed were divided into 3 main themes. The themes are the existing simulation session, simulation as a support tool in the transition program and the impact of simulation on novice nurses. Conclusion In summary, each simulation type has its learning domain. The effectiveness of the simulation will much depend on the appropriate simulation type selection

Landscape-level controls on dissolved carbon flux from diverse catchments of the circumboreal

Author Posting. © American Geophysical Union, 2012. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Global Biogeochemical Cycles 26 (2012): GB0E02, doi:10.1029/2012GB004299.While much of the dissolved organic carbon (DOC) within rivers is destined for mineralization to CO2, a substantial fraction of riverine bicarbonate (HCO3−) flux represents a CO2 sink, as a result of weathering processes that sequester CO2 as HCO3−. We explored landscape-level controls on DOC and HCO3− flux in subcatchments of the boreal, with a specific focus on the effect of permafrost on riverine dissolved C flux. To do this, we undertook a multivariate analysis that partitioned the variance attributable to known, key regulators of dissolved C flux (runoff, lithology, and vegetation) prior to examining the effect of permafrost, using riverine biogeochemistry data from a suite of subcatchments drawn from the Mackenzie, Yukon, East, and West Siberian regions of the circumboreal. Across the diverse catchments that we study, controls on HCO3− flux were near-universal: runoff and an increased carbonate rock contribution to weathering (assessed as riverwater Ca:Na) increased HCO3− yields, while increasing permafrost extent was associated with decreases in HCO3−. In contrast, permafrost had contrasting and region-specific effects on DOC yield, even after the variation caused by other key drivers of its flux had been accounted for. We used ionic ratios and SO4 yields to calculate the potential range of CO2 sequestered via weathering across these boreal subcatchments, and show that decreasing permafrost extent is associated with increases in weathering-mediated CO2 fixation across broad spatial scales, an effect that could counterbalance some of the organic C mineralization that is predicted with declining permafrost.Funding for this work was provided through NSF-OPP-0229302 and NSF-OPP-0732985. Additional support to S.E.T. was provided by an NSERC Postdoctoral Fellowship.2013-02-2

Isotopic evidence for the contemporary origin of high-molecular weight organic matter in oceanic environments

Previous work has suggested that apparent old C-14 ages for oceanic DOC are the result of mixing of different organic carbon fractions. This report provides direct evidence for a contemporary C-14 age of a high-molecular-weight (HMW) fraction of colloidal organic carbon (greater than or equal to 10 kD). Colloidal organic matter, COM(10) (from 10 kDaltons (kD) to 0.2 mu m), isolated from the upper water column of the Gulf of Mexico and the Middle Atlantic Bight (MAB) region, generally has a contemporary age (i.e., younger than a few decades), while COM(1) (from 1 kD to 0.2 mu m), is apparently old: 380-4500 y BP. Thus, HMW COM(10) (3-5% of DOC) from the upper water column is derived from living particulate organic matter (POM) and cycles rapidly, while a significant fraction of low-molecular-weight (less than or equal to 1 kD) DOM is likely more refractory, and cycles on much longer time scales. The presence of pigment biomarker compounds in COM(1) from the upper water column points to selected phytoplankton species as one of the sources of COM. Terrestrial carbon as another source of COM is suggested from the inverse correlation between Delta(14)C and delta(13)C values, as well as the increasing delta(13)C values with increasing salinity. Th-234-derived turnover times of COM(10) and COM(1) from both the Gulf of Mexico and MAB are consistently short, 1-20 and 3-30 days, respectively. These short residence times support the hypothesis that C-14 ages of colloidal fractions of DOC are the result of COM fractions being a mixture of several endmembers with fast and slow turnover rates

Single Particle Difraction at FLASH

Single-pulse coherent diffraction patterns have been collected from randomly injected single particles with a soft X-ray free-electron laser (FEL). The intense focused FEL pulse gives a high-resolution low-noise coherent diffraction pattern of the object before that object turns into a plasma and explodes. A diffraction pattern of a single particle will only be recorded when the particle arrival into the FEL interaction region coincides with FEL pulse arrival and detector integration. The properties of the experimental apparatus coinciding with these three events set the data acquisition rate. For our single particle FLASH diffraction imaging experiments: (1) an aerodynamic lens stack prepared a particle beam that consisted of particles moving at 150-200 m/s positioned randomly in space and time, (2) the 10 fs long FEL pulses were delivered at a fixed rate, and (3) the detector was set to integrate and readout once every two seconds. The effect of these experimental parameters on the rate of data acquisition using randomly injected particles will be discussed. Overall, the ultrashort FEL pulses do not set the limit of the data acquisition, more important is the effective interaction time of the particle crossing the FEL focus, the pulse sequence structure and the detector readout rate. Example diffraction patterns of randomly injected ellipsoidal iron oxide nanoparticles in different orientations are presented. This is the first single particle diffraction data set of identical particles in different orientations collected on a shot-to-shot basis. This data set will be used to test algorithms for recovering 3D structure from single particle diffraction