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Sample records for ad brain samples

  1. Natural Radioactivity of Boron Added Clay Samples

    SciTech Connect

    Akkurt, I.; Guenoglu, K.; Canakcii, H.; Mavi, B.

    2011-12-26

    Clay, consisting fine-grained minerals, is an interesting materials and can be used in a variety of different fields especially in dermatology application. Using clay such a field it is important to measure its natural radioactivity. Thus the purpose of this study is to measure {sup 226}Ra, {sup 232}Th and {sup 40}K concentration in clay samples enriched with boron. Three different types of clay samples were prepared where boron is used in different rate. The measurements have been determined using a gamma-ray spectrometry consists of a 3''x3'' NaI(Tl) detector. From the measured activity the radium equivalent activities (Ra{sub eq}), external hazard index (H{sub ex}), absorbed dose rate in air (D) and annual effective dose (AED) have also been obtained.

  2. Natural Radioactivity of Boron Added Clay Samples

    NASA Astrophysics Data System (ADS)

    Akkurt, I.; ćanakciı, H.; Mavi, B.; Günoǧlu, K.

    2011-12-01

    Clay, consisting fine-grained minerals, is an interesting materials and can be used in a variety of diferent fields especially in dermatology application. Using clay such a field it is important to measure its natural radioacitivty. Thus the purpose of this study is to measure 226Ra, 232Th and 40K concentration in clay samples enriched with boron. Three different types of clay samples were prepared where boron is used in different rate. The measurements have been determined using a gamma-ray spectrometry consists of a 3″×3″ NaI(Tl) detector. From the measured activity the radium equivalent activities (Raeq), external hazard index (Hex), absorbed dose rate in air (D) and annual effective dose (AED) have also been obtained.

  3. Differential Impact of Whole-Brain Radiotherapy Added to Radiosurgery for Brain Metastases

    SciTech Connect

    Kong, Doo-Sik; Lee, Jung-Il; Im, Yong-Seok; Nam, Do-Hyun; Park, Kwan; Kim, Jong-Hyun

    2010-10-01

    Purpose: The authors investigated whether the addition of whole-brain radiotherapy (WBRT) to stereotactic radiosurgery (SRS) provided any therapeutic benefit according to recursive partitioning analysis (RPA) class. Methods and Materials: Two hundred forty-five patients with 1 to 10 metastases who underwent SRS between January 2002 and December 2007 were included in the study. Of those, 168 patients were treated with SRS alone and 77 patients received SRS followed by WBRT. Actuarial curves were estimated using the Kaplan-Meier method regarding overall survival (OS), distant brain control (DC), and local brain control (LC) stratified by RPA class. Analyses for known prognostic variables were performed using the Cox proportional hazards model. Results: Univariate and multivariate analysis revealed that control of the primary tumor, small number of brain metastases, Karnofsky performance scale (KPS) > 70, and initial treatment modalities were significant predictors for survival. For RPA class 1, SRS plus WBRT was associated with a longer survival time compared with SRS alone (854 days vs. 426 days, p = 0.042). The SRS plus WBRT group also showed better LC rate than did the SRS-alone group (p = 0.021), although they did not show a better DC rate (p = 0.079). By contrast, for RPA class 2 or 3, no significant difference in OS, LC, or DC was found between the two groups. Conclusions: These results suggest that RPA classification should determine whether or not WBRT is added to SRS. WBRT may be recommended to be added to SRS for patients in whom long-term survival is expected on the basis of RPA classification.

  4. Targeting modulates audiences' brain and behavioral responses to safe sex video ads.

    PubMed

    Wang, An-Li; Lowen, Steven B; Shi, Zhenhao; Bissey, Bryn; Metzger, David S; Langleben, Daniel D

    2016-10-01

    Video ads promoting condom use are a key component of media campaigns to stem the HIV epidemic. Recent neuroimaging studies in the context of smoking cessation, point to personal relevance as one of the key variables that determine the effectiveness of public health messages. While minority men who have sex with men (MSM) are at the highest risk of HIV infection, most safe-sex ads feature predominantly Caucasian actors in heterosexual scenarios. We compared brain respons of 45 African American MSM to safe sex ads that were matched (i.e. 'Targeted') to participants' sexual orientation and race, and 'Untargeted' ads that were un matched for these characteristics. Ad recall, perceived 'convincingness' and attitudes towards condom use were also assessed. We found that Targeted ads were better remembered than the Untargeted ads but perceived as equally convincing. Targeted ads engaged brain regions involved in self-referential processing and memory, including the amygdala, hippocampus, temporal and medial prefrontal cortices (MPFC) and the precuneus. Connectivity between MPFC and precuneus and middle temporal gyrus was stronger when viewing Targeted ads. Our results suggest that targeting may increase cognitive processing of safe sex ads and justify further prospective studies linking brain response to media public health interventions and clinical outcomes. PMID:27217112

  5. Targeting modulates audiences' brain and behavioral responses to safe sex video ads.

    PubMed

    Wang, An-Li; Lowen, Steven B; Shi, Zhenhao; Bissey, Bryn; Metzger, David S; Langleben, Daniel D

    2016-10-01

    Video ads promoting condom use are a key component of media campaigns to stem the HIV epidemic. Recent neuroimaging studies in the context of smoking cessation, point to personal relevance as one of the key variables that determine the effectiveness of public health messages. While minority men who have sex with men (MSM) are at the highest risk of HIV infection, most safe-sex ads feature predominantly Caucasian actors in heterosexual scenarios. We compared brain respons of 45 African American MSM to safe sex ads that were matched (i.e. 'Targeted') to participants' sexual orientation and race, and 'Untargeted' ads that were un matched for these characteristics. Ad recall, perceived 'convincingness' and attitudes towards condom use were also assessed. We found that Targeted ads were better remembered than the Untargeted ads but perceived as equally convincing. Targeted ads engaged brain regions involved in self-referential processing and memory, including the amygdala, hippocampus, temporal and medial prefrontal cortices (MPFC) and the precuneus. Connectivity between MPFC and precuneus and middle temporal gyrus was stronger when viewing Targeted ads. Our results suggest that targeting may increase cognitive processing of safe sex ads and justify further prospective studies linking brain response to media public health interventions and clinical outcomes.

  6. Label-free imaging and quantitative chemical analysis of Alzheimer's disease brain samples with multimodal multiphoton nonlinear optical microspectroscopy

    NASA Astrophysics Data System (ADS)

    Lee, Jang Hyuk; Kim, Dae Hwan; Song, Woo Keun; Oh, Myoung-Kyu; Ko, Do-Kyeong

    2015-05-01

    We developed multimodal multiphoton microspectroscopy using a small-diameter probe with gradient-index lenses and applied it to unstained Alzheimer's disease (AD) brain samples. Our system maintained the image quality and spatial resolution of images obtained using an objective lens of similar numerical aperture. Multicolor images of AD brain samples were obtained simultaneously by integrating two-photon excited fluorescence and second-harmonic generation on a coherent anti-Stokes Raman scattering (CARS) microendoscope platform. Measurements of two hippocampal regions, the cornus ammonis-1 and dentate gyrus, revealed more lipids, amyloid fibers, and collagen in the AD samples than in the normal samples. Normal and AD brains were clearly distinguished by a large spectral difference and quantitative analysis of the CH mode using CARS microendoscope spectroscopy. We expect this system to be an important diagnosis tool in AD research.

  7. Label-free imaging and quantitative chemical analysis of Alzheimer's disease brain samples with multimodal multiphoton nonlinear optical microspectroscopy.

    PubMed

    Lee, Jang Hyuk; Kim, Dae Hwan; Song, Woo Keun; Oh, Myoung-Kyu; Ko, Do-Kyeong

    2015-05-01

    We developed multimodal multiphoton microspectroscopy using a small-diameter probe with gradient-index lenses and applied it to unstained Alzheimer's disease (AD) brain samples. Our system maintained the image quality and spatial resolution of images obtained using an objective lens of similar numerical aperture. Multicolor images of AD brain samples were obtained simultaneously by integrating two-photon excited fluorescence and second-harmonic generation on a coherent anti-Stokes Raman scattering (CARS) microendoscope platform. Measurements of two hippocampal regions, the cornus ammonis-1 and dentate gyrus, revealed more lipids, amyloid fibers, and collagen in the AD samples than in the normal samples. Normal and AD brains were clearly distinguished by a large spectral difference and quantitative analysis of the CH mode using CARS microendoscope spectroscopy. We expect this system to be an important diagnosis tool in AD research

  8. Obesity is linked with lower brain volume in 700 AD and MCI patients

    PubMed Central

    Ho, April J.; Raji, Cyrus A.; Becker, James T.; Lopez, Oscar L.; Kuller, Lewis H.; Hua, Xue; Lee, Suh; Hibar, Derrek; Dinov, Ivo D.; Stein, Jason L.; Jack, Clifford R.; Weiner, Michael W.; Toga, Arthur W.; Thompson, Paul M.

    2011-01-01

    Obesity is associated with lower brain volumes in cognitively normal elderly subjects, but no study has yet investigated the effects of obesity on brain structure in patients with mild cognitive impairment (MCI) or Alzheimer’s disease (AD). To determine if higher body mass index (BMI) is associated with brain volume deficits in cognitively impaired elderly subjects, we analyzed brain magnetic resonance imaging (MRI) scans of 700 MCI or AD patients from two different cohorts: the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and the Cardiovascular Health Study-Cognition Study (CHS-CS). Tensor-based morphometry (TBM) was used to create 3-dimensional maps of regional tissue excess or deficits in subjects with MCI (ADNI, N=399; CHS, N=77) and AD (ADNI, N=188; CHS, N=36). In both AD and MCI groups, higher BMI was associated with brain volume deficits in frontal, temporal, parietal, and occipital lobes; the atrophic pattern was consistent in both ADNI and CHS populations. Cardiovascular risk factors, especially obesity, should be considered as influencing brain structure in those already afflicted by cognitive impairment and dementia. PMID:20570405

  9. Neurodegeneration and Alzheimer's disease (AD). What Can Proteomics Tell Us About the Alzheimer's Brain?

    PubMed

    Moya-Alvarado, Guillermo; Gershoni-Emek, Noga; Perlson, Eran; Bronfman, Francisca C

    2016-02-01

    Neurodegenerative diseases, such as Alzheimer's diseases (AD), are becoming more prevalent as the population ages. However, the mechanisms that lead to synapse destabilization and neuron death remain elusive. The advent of proteomics has allowed for high-throughput screening methods to search for biomarkers that could lead to early diagnosis and treatment and to identify alterations in the cellular proteome that could provide insight into disease etiology and possible treatment avenues. In this review, we have concentrated mainly on the findings that are related to how and whether proteomics studies have contributed to two aspects of AD research, the development of biomarkers for clinical diagnostics, and the recognition of proteins that can help elucidate the pathways leading to AD brain pathology. As a result of these studies, several candidate cerebrospinal fluid biomarkers are now available for further validation in different AD cohorts. Studies in AD brain and AD transgenic models support the notion that oxidative damage results in the alterations of metabolic enzymes and that mitochondrial dysfunction is central to AD neuropathology. PMID:26657538

  10. Study of amyloid-β peptide functional brain networks in AD, MCI and HC.

    PubMed

    Jiang, Jiehui; Duan, Huoqiang; Huang, Zheming; Yu, Zhihua

    2015-01-01

    One medical challenge in studying the amyloid-β (Aβ) peptide mechanism for Alzheimer's disease (AD) is exploring the law of beta toxic oligomers' diffusion in human brains in vivo. One beneficial means of solving this problem is brain network analysis based on graph theory. In this study, the characteristics of Aβ functional brain networks of Healthy Control (HC), Mild Cognitive Impairment (MCI), and AD groups were compared by applying graph theoretical analyses to Carbon 11-labeled Pittsburgh compound B positron emission tomography (11C PiB-PET) data. 120 groups of PiB-PET images from the ADNI database were analyzed. The results showed that the small-world property of MCI and AD were lost as compared to HC. Furthermore, the local clustering of networks was higher in both MCI and AD as compared to HC, whereas the path length was similar among the three groups. The results also showed that there could be four potential Aβ toxic oligomer seeds: Frontal_Sup_Medial_L, Parietal_Inf_L, Frontal_Med_Orb_R, and Parietal_Inf_R. These four seeds are corresponding to Regions of Interests referred by physicians to clinically diagnose AD.

  11. Study of amyloid-β peptide functional brain networks in AD, MCI and HC.

    PubMed

    Jiang, Jiehui; Duan, Huoqiang; Huang, Zheming; Yu, Zhihua

    2015-01-01

    One medical challenge in studying the amyloid-β (Aβ) peptide mechanism for Alzheimer's disease (AD) is exploring the law of beta toxic oligomers' diffusion in human brains in vivo. One beneficial means of solving this problem is brain network analysis based on graph theory. In this study, the characteristics of Aβ functional brain networks of Healthy Control (HC), Mild Cognitive Impairment (MCI), and AD groups were compared by applying graph theoretical analyses to Carbon 11-labeled Pittsburgh compound B positron emission tomography (11C PiB-PET) data. 120 groups of PiB-PET images from the ADNI database were analyzed. The results showed that the small-world property of MCI and AD were lost as compared to HC. Furthermore, the local clustering of networks was higher in both MCI and AD as compared to HC, whereas the path length was similar among the three groups. The results also showed that there could be four potential Aβ toxic oligomer seeds: Frontal_Sup_Medial_L, Parietal_Inf_L, Frontal_Med_Orb_R, and Parietal_Inf_R. These four seeds are corresponding to Regions of Interests referred by physicians to clinically diagnose AD. PMID:26405999

  12. Brain areas involved in the acupuncture treatment of AD model rats: a PET study

    PubMed Central

    2014-01-01

    Background Acupuncture may effectively treat certain symptoms of Alzheimer’s disease (AD). Although several studies have used functional brain imaging to investigate the mechanisms of acupuncture treatment on AD, these mechanisms are still poorly understood. We therefore further explored the mechanism by which needling at ST36 may have a therapeutic effect in a rat AD model. Methods A total of 80 healthy Wistar rats were divided into healthy control (n = 15) and pre-model (n = 65) groups. After inducing AD-like disease, a total of 45 AD model rats were randomly divided into three groups: the model group (n = 15), the sham-point group (n = 15), and the ST36 group (n = 15). The above three groups underwent PET scanning. PET images were processed with SPM2. Results The brain areas that were activated in the sham-point group relative to the model group were primarily centred on the bilateral limbic system, the right frontal lobe, and the striatum, whereas the activated areas in the ST36 group were primarily centred on the bilateral limbic system (pyriform cortex), the bilateral temporal lobe (olfactory cortex), the right amygdala and the right hippocampus. Compared with the sham-point group, the ST36 group showed greater activation in the bilateral amygdalae and the left temporal lobe. Conclusion We concluded that needling at a sham point or ST36 can increase blood perfusion and glycol metabolism in certain brain areas, and thus may have a positive influence on the cognition of AD patients. PMID:24886495

  13. Identification of N-terminally truncated pyroglutamate amyloid-β in cholesterol-enriched diet-fed rabbit and AD brain.

    PubMed

    Perez-Garmendia, Roxanna; Hernandez-Zimbron, Luis Fernando; Morales, Miguel Angel; Luna-Muñoz, José; Mena, Raul; Nava-Catorce, Miriam; Acero, Gonzalo; Vasilevko, Vitaly; Viramontes-Pintos, Amparo; Cribbs, David H; Gevorkian, Goar

    2014-01-01

    The main amyloid-β peptide (Aβ) variants detected in the human brain are Aβ1-40 and Aβ1-42; however, a significant proportion of Aβ in Alzheimer's disease (AD) brain also consists of N-terminal truncated/modified species. AβN3(pE), Aβ peptide bearing amino-terminal pyroglutamate at position 3, has been demonstrated to be a major N-truncated/modified constituent of intracellular, extracellular, and vascular Aβ deposits in AD and Down syndrome brain tissue. It has been previously demonstrated that rabbits fed a diet enriched in cholesterol and given water containing trace copper levels developed AD-like pathology including intraneuronal and extracellular Aβ accumulation, tau hyperphosphorylation, vascular inflammation, astrocytosis, microgliosis, reduced levels of acetylcholine, as well as learning deficits and thus, may be used as a non-transgenic animal model of sporadic AD. In the present study, we have demonstrated for the first time the presence of AβN3(pE) in blood vessels in cholesterol-enriched diet-fed rabbit brain. In addition, we detected AβN3(pE) immunoreactivity in all postmortem AD brain samples studied. We believe that our results are potentially important for evaluation of novel therapeutic molecules/strategies targeting Aβ peptides in a suitable non-transgenic animal model.

  14. The role of metals in modulating metalloprotease activity in the AD brain.

    PubMed

    Filiz, Gulay; Price, Katherine A; Caragounis, Aphrodite; Du, Tai; Crouch, Peter J; White, Anthony R

    2008-03-01

    Biometals such as copper and zinc have an important role in Alzheimer's disease (AD). Accumulating evidence indicates that copper homeostasis is altered in AD brain with elevated extracellular and low intracellular copper levels. Studies in animals and cell cultures have suggested that increasing intracellular copper can ameliorate AD-like pathology including amyloid deposition and tau phosphorylation. Modulating copper homeostasis can also improve cognitive function in animal models of AD. Treatments are now being developed that may result in redistribution of copper within the brain. Metal ligands such as clioquinol (CQ), DP-109 or pyrrolidine dithiocarbamate (PDTC) have shown promising results in animal models of AD, however, the actual mode of action in vivo has not been fully determined. We previously reported that CQ-metal complexes were able to increase intracellular copper levels in vitro. This resulted in stimulation of phosphoinositol-3-kinase activity and mitogen activated protein kinases (MAPK). Increased kinase activity resulted in up-regulated matrix metalloprotease (MMP2 and MMP3) activity resulting in enhanced degradation of secreted A beta. These findings are consistent with previous studies reporting metal-mediated activation of MAPKs and MMPs. How this activation occurs is unknown but evidence suggests that copper may be able to activate membrane receptors such as the epidermal growth factor receptor (EGFR) and result in downstream activation of MAPK pathways. This has been supported by studies showing metal-mediated activation of EGFR through ligand-independent processes in a number of cell-types. Our initial studies reveal that copper complexes can in fact activate EGFR. However, further studies are necessary to determine if metal complexes such as CQ-copper induce up-regulation of A beta-degrading MMP activity through this mechanism. Elucidation of this pathway may have important implications for the development of metal ligand based

  15. Brain cholinesterases: III. Future perspectives of AD research and clinical practice.

    PubMed

    Shen, Z-X

    2004-01-01

    Alzheimer's disease (AD) is initially and primarily associated with the degeneration and alteration in the metabolism of cholinesterases (ChEs). The use of ChEs inhibitors to treat Alzheimer's condition, on the basis of the cholinergic hypothesis of the disease, is, therefore, without grounds. Most disturbing is the fact that the currently available anti-ChEs are designed to inhibit normal ChEs in the brain and throughout the body, but not the abnormal ones. Based on the acetylcholinesterase (AChE) deficiency theory, treatment should be designed to protect the cranial ChEs system from alteration and/or to help that system fight against degeneration through restoring its homeostatic action for brain structure and function instead. The overlap in the clinical, biochemical, molecular-cellular, and pathological alterations seen in patients with AD and individuals with many other brain disorders, which has bewildered many investigators, may now be explained by the shared underlying mismetabolism of brain ChEs. The abnormal metabolism of ChEs existing in asymptomatic subjects may indicate that the system is "at risk" and deserves serious attention. Future perspectives of ChEs research in vivo and in vitro in connection with AD and clinical diagnosis, prevention and treatment are proposed. Several potentially useful therapeutic and preventive means and pharmacological agents in this regard are identified and discussed, such as physical and intellectual stimulation, and a class of drugs including vitamin E, R-(-)-deprenyl (deprenyl, selegiline), acetyl L-carnitine, cytidine diphosphocholine (CDP-choline), centrophenoxine, L-phenylalanine, naloxone, galactose, and lithium, that have been proven to be able to stimulate AChE activity. Their working mechanisms may be through directly changing the configuration of AChE molecules and/or correcting micro- and overall environmental biological conditions for ChEs.

  16. In vitro determination of normal and neoplastic human brain tissue optical properties using inverse adding-doubling.

    PubMed

    Gebhart, S C; Lin, W C; Mahadevan-Jansen, A

    2006-04-21

    To complement a project towards the development of real-time optical biopsy for brain tissue discrimination and surgical resection guidance, the optical properties of various brain tissues were measured in vitro and correlated to features within clinical diffuse reflectance tissue spectra measured in vivo. Reflectance and transmission spectra of in vitro brain tissue samples were measured with a single-integrating-sphere spectrometer for wavelengths 400-1300 nm and converted to absorption and reduced scattering spectra using an inverse adding-doubling technique. Optical property spectra were classified as deriving from white matter, grey matter or glioma tissue according to histopathologic diagnosis, and mean absorption and reduced scattering spectra were calculated for the three tissue categories. Absolute reduced scattering and absorption values and their relative differences between histopathological groups agreed with previously reported results with the exception that absorption coefficients were often overestimated, most likely due to biologic variability or unaccounted light loss during reflectance/transmission measurement. Absorption spectra for the three tissue classes were dominated by haemoglobin absorption below 600 nm and water absorption above 900 nm and generally determined the shape of corresponding clinical diffuse reflectance spectra. Reduced scattering spectral shapes followed the power curve predicted by the Rayleigh limit of Mie scattering theory. While tissue absorption governed the shape of clinical diffuse reflectance spectra, reduced scattering determined their relative emission intensities between the three tissue categories. PMID:16585842

  17. The gut-brain axis rewired: adding a functional vagal nicotinic "sensory synapse".

    PubMed

    Perez-Burgos, Azucena; Mao, Yu-Kang; Bienenstock, John; Kunze, Wolfgang A

    2014-07-01

    It is generally accepted that intestinal sensory vagal fibers are primary afferent, responding nonsynaptically to luminal stimuli. The gut also contains intrinsic primary afferent neurons (IPANs) that respond to luminal stimuli. A psychoactive Lactobacillus rhamnosus (JB-1) that affects brain function excites both vagal fibers and IPANs. We wondered whether, contrary to its primary afferent designation, the sensory vagus response to JB-1 might depend on IPAN to vagal fiber synaptic transmission. We recorded ex vivo single- and multiunit afferent action potentials from mesenteric nerves supplying mouse jejunal segments. Intramural synaptic blockade with Ca(2+) channel blockers reduced constitutive or JB-1-evoked vagal sensory discharge. Firing of 60% of spontaneously active units was reduced by synaptic blockade. Synaptic or nicotinic receptor blockade reduced firing in 60% of vagal sensory units that were stimulated by luminal JB-1. In control experiments, increasing or decreasing IPAN excitability, respectively increased or decreased nerve firing that was abolished by synaptic blockade or vagotomy. We conclude that >50% of vagal afferents function as interneurons for stimulation by JB-1, receiving input from an intramural functional "sensory synapse." This was supported by myenteric plexus nicotinic receptor immunohistochemistry. These data offer a novel therapeutic target to modify pathological gut-brain axis activity.-Perez-Burgos, A., Mao, Y.-K., Bienenstock, J., Kunze, W. A. The gut-brain axis rewired: adding a functional vagal nicotinic "sensory synapse."

  18. Sampling and major element chemistry of the recent (A.D. 1631-1944) Vesuvius activity

    USGS Publications Warehouse

    Belkin, H.E.; Kilburn, C.R.J.; de Vivo, B.

    1993-01-01

    Detailed sampling of the Vesuvius lavas erupted in the period A.D. 1631-1944 provides a suite of samples for comprehensive chemical analyses and related studies. Major elements (Si, Ti, Al, Fetotal, Mn, Mg, Ca, Na, K and P), volatile species (Cl, F, S, H2O+, H2O- and CO2), and ferrous iron (Fe2+) were determined for one hundred and forty-nine lavas and five tephra from the A.D. 1631-1944 Vesuvius activity. The lavas represent a relatively homogeneous suite with respect to SiO2, TiO2, FeOtotal, MnO and P2O5, but show systematic variations among MgO, K2O, Na2O, Al2O3 and CaO. The average SiO2 content is 48.0 wt.% and the rocks are classified as tephriphonolites according to their content of alkalis. All of the lavas are silica-undersaturated and are nepheline, leucite, and olivine normative. There is no systematic variation in major-element composition with time, over the period A.D. 1631-1944. The inter-eruption and intra-eruption compositional differences are the same magnitude. The lavas are highly porphyritic with clinopyroxene and leucite as the major phases. Fractionation effects are not reflected in the silica content of the lavas. The variability of MgO, K2O, Na2O, and CaO can be modelled as a relative depletion or accumulation of clinopyroxene. ?? 1993.

  19. Alteration of mTOR signaling occurs early in the progression of Alzheimer disease (AD): analysis of brain from subjects with pre-clinical AD, amnestic mild cognitive impairment and late-stage AD.

    PubMed

    Tramutola, Antonella; Triplett, Judy C; Di Domenico, Fabio; Niedowicz, Dana M; Murphy, Michael P; Coccia, Raffaella; Perluigi, Marzia; Butterfield, D Allan

    2015-06-01

    The clinical symptoms of Alzheimer disease (AD) include a gradual memory loss and subsequent dementia, and neuropathological deposition of senile plaques and neurofibrillary tangles. At the molecular level, AD subjects present overt amyloid β (Aβ) production and tau hyperphosphorylation. Aβ species have been proposed to overactivate the phosphoinositide3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) axis, which plays a central role in proteostasis. The current study investigated the status of the PI3K/Akt/mTOR pathway in post-mortem tissue from the inferior parietal lobule (IPL) at three different stages of AD: late AD, amnestic mild cognitive impairment (MCI) and pre-clinical AD (PCAD). Our findings suggest that the alteration of mTOR signaling and autophagy occurs at early stages of AD. We found a significant increase in Aβ (1-42) levels, associated with reduction in autophagy (Beclin-1 and LC-3) observed in PCAD, MCI, and AD subjects. Related to the autophagy impairment, we found a hyperactivation of PI3K/Akt/mTOR pathway in IPL of MCI and AD subjects, but not in PCAD, along with a significant decrease in phosphatase and tensin homolog. An increase in two mTOR downstream targets, p70S6K and 4EBP1, occurred in AD and MCI subjects. Both AD and MCI subjects showed increased, insulin receptor substrate 1, a candidate biomarker of brain insulin resistance, and GSK-3β, a kinase targeting tau phosphorylation. Nevertheless, tau phosphorylation was increased in the clinical groups. The results hint at a link between Aβ and the PI3K/Akt/mTOR axis and provide further insights into the relationship between AD pathology and insulin resistance. In addition, we speculate that the alteration of mTOR signaling in the IPL of AD and MCI subjects, but not in PCAD, is due to the lack of substantial increase in oxidative stress. The figure represents the three different stages of Alzheimer Disease: Preclinical Alzheimer Disease (PCAD), Mild cognitive impairment (MCI

  20. Odontometric sex discrimination in the Herculaneum sample (79 AD, Naples, Italy), with application to juveniles.

    PubMed

    Viciano, Joan; Alemán, Inmaculada; D'Anastasio, Ruggero; Capasso, Luigi; Botella, Miguel C

    2011-05-01

    Sex determination of subadult skeletal remains with satisfactory accuracy represents one of the most important limitations of archaeological research and forensic practice. Teeth are one of the most durable physical elements of an individual that remain after death, and constitute a potential source of information about the biological sex of that individual. This study was based on the skeletal remains of 117 individuals from the ancient city of Herculaneum (Naples, Italy), victims of the eruption of the nearby volcano Vesuvius on 24/25 August, 79 AD. It has been possible to develop discriminant function formulae based on dental dimensions of adult individuals whose sex had previously been determined based on descriptive osteologic criteria. These formulae were subsequently applied to the permanent dentitions of immature individuals of the same population in order to estimate their sex. The results show that the canine is the tooth with the greatest sex dimorphism in adults, providing percentages of correct assignment of sex between 76.5% and 100% depending on the dimension used. Of the 30 subadult individuals in the target sample, estimation of sex was possible for 22 individuals. Sex assignments matched those determined from descriptive characteristics of the ilia and mandible in 73.33% of the cases. The results provide some optimism that this method may be applicable to juvenile archaeological samples.

  1. PAK Inactivation Impairs Social Recognition in 3xTg-AD Mice without Increasing Brain Deposition of Tau and Aβ

    PubMed Central

    Arsenault, Dany; Dal-Pan, Alexandre; Tremblay, Cyntia; Bennett, David A.; Guitton, Matthieu J.; De Koninck, Yves; Tonegawa, Susumu

    2013-01-01

    Defects in p21-activated kinase (PAK) are suspected to play a role in cognitive symptoms of Alzheimer's disease (AD). Dysfunction in PAK leads to cofilin activation, drebrin displacement from its actin-binding site, actin depolymerization/severing, and, ultimately, defects in spine dynamics and cognitive impairment in mice. To determine the role of PAK in AD, we first quantified PAK by immunoblotting in homogenates from the parietal neocortex of subjects with a clinical diagnosis of no cognitive impairment (n = 12), mild cognitive impairment (n = 12), or AD (n = 12). A loss of total PAK, detected in the cortex of AD patients (−39% versus controls), was correlated with cognitive impairment (r2 = 0.148, p = 0.027) and deposition of total and phosphorylated tau (r2 = 0.235 and r2 = 0.206, respectively), but not with Aβ42 (r2 = 0.056). Accordingly, we found a decrease of total PAK in the cortex of 12- and 20-month-old 3xTg-AD mice, an animal model of AD-like Aβ and tau neuropathologies. To determine whether PAK dysfunction aggravates AD phenotype, 3xTg-AD mice were crossed with dominant-negative PAK mice. PAK inactivation led to obliteration of social recognition in old 3xTg-AD mice, which was associated with a decrease in cortical drebrin (−25%), but without enhancement of Aβ/tau pathology or any clear electrophysiological signature. Overall, our data suggest that PAK decrease is a consequence of AD neuropathology and that therapeutic activation of PAK may exert symptomatic benefits on high brain function. PMID:23804095

  2. Early inflammation and immune response mRNAs in the brain of AD11 anti-NGF mice.

    PubMed

    D'Onofrio, Mara; Arisi, Ivan; Brandi, Rossella; Di Mambro, Alessandra; Felsani, Armando; Capsoni, Simona; Cattaneo, Antonino

    2011-06-01

    We characterized the gene expression profile of brain regions at an early stage of the Alzheimer's like neurodegeneration in the anti-NGF AD11 model. Total RNA was extracted from hippocampus, cortex and basal forebrain of postnatal day 30 (P30) and postnatal day 90 (P90) mice and expression profiles were studied by microarray analysis, followed by qRT-PCR validation of 243 significant candidates. Wide changes in gene expression profiles occur already at P30. As expected, cholinergic system and neurotrophins related genes expression were altered. Interestingly, the most significantly affected clusters of mRNAs are linked to inflammation and immune response, as well as to Wnt signaling. mRNAs encoding for different complement factors show a large differential expression. This is noteworthy, since these complement cascade proteins are involved in CNS synapse elimination, during normal brain developing and in neurodegenerative diseases. This gene expression pattern highlights that an early event in AD11 neurodegeneration is represented, together with neurotrophic deficits and synaptic remodeling, by an inflammatory response and an unbalance in the immunotrophic state of the brain. These might be key events in the pathogenesis and development of AD.

  3. Statistical Voxel-Based Methods and [18F]FDG PET Brain Imaging: Frontiers for the Diagnosis of AD.

    PubMed

    Gallivanone, Francesca; Della Rosa, Pasquale Anthony; Castiglioni, Isabella

    2016-01-01

    Recommended guidelines for the diagnosis of dementia due to Alzheimer's Disease (AD) were revised in recent years, including Positron Emission Tomography (PET) as an in-vivo diagnostic imaging technique for the diagnosis of neurodegeneration. In particular PET, using 18Ffluorodeoxiglucouse ([18F]FDG), is able to detect very early changes of glucose consumption at the synaptic level, enabling to support both early and differential diagnosis of AD. In standard clinical practice, interpretation of [18F] FDG-PET images is usually achieved through qualitative assessment. Visual inspection although only reveals information visible at human eyes resolution, while information at a higher resolution is missed. Furthermore, qualitative assessment depends on the degree of expertise of the clinician, preventing from the definition of accurate and standardized imaging biomarkers. Automated and computerized image processing methods have been proposed to support the in-vivo assessment of brain PET studies. In particular, objective statistical image analyses, enabling the comparison of one patient's images to a group of control images have been shown to carry important advantages for detecting significant metabolic changes, including the availability of more objective, cross-center reliable metrics and the detectability of brain subtle functional changes, as occurring in prodromal AD. The purpose of the current review is to provide a systematic overview encompassing the frontiers recently reached by quantitative approaches for the statistical analysis of PET brain images in the study of AD, with a particular focus on Statistical Parametric Mapping. Main achievements, e.g. in terms of standardized biomarkers of AD as well as of sensitivity and specificity, will be discussed. PMID:26567733

  4. Ad cerebrum per scientia: Ira Hirsh, psychoacoustics, and new approaches to understanding the human brain

    NASA Astrophysics Data System (ADS)

    Lauter, Judith

    2002-05-01

    As Research Director of CID, Ira emphasized the importance of combining information from biology with rigorous studies of behavior, such as psychophysics, to better understand how the brain and body accomplish the goals of everyday life. In line with this philosophy, my doctoral dissertation sought to explain brain functional asymmetries (studied with dichotic listening) in terms of the physical dimensions of a library of test sounds designed to represent a speech-music continuum. Results highlighted individual differences plus similarities in terms of patterns of relative ear advantages, suggesting an organizational basis for brain asymmetries depending on physical dimensions of stimulus and gesture with analogs in auditory, visual, somatosensory, and motor systems. My subsequent work has employed a number of noninvasive methods (OAEs, EPs, qEEG, PET, MRI) to explore the neurobiological bases of individual differences in general and functional asymmetries in particular. This research has led to (1) the AXS test battery for assessing the neurobiology of human sensory-motor function; (2) the handshaking model of brain function, describing dynamic relations along all three body/brain axes; (3) the four-domain EPIC model of functional asymmetries; and (4) the trimodal brain, a new model of individual differences based on psychoimmunoneuroendocrinology.

  5. Adding chemo after radiation treatment improves survival for adults with a type of brain tumor

    Cancer.gov

    Adults with low-grade gliomas, a form of brain tumor, who received chemotherapy following completion of radiation therapy lived longer than patients who received radiation therapy alone, according to long-term follow-up results from a NIH-supported random

  6. Inhibition of acetylcholinesterase in CSF versus brain assessed by 11C-PMP PET in AD patients treated with galantamine.

    PubMed

    Darreh-Shori, T; Kadir, A; Almkvist, O; Grut, M; Wall, A; Blomquist, G; Eriksson, B; Långström, B; Nordberg, A

    2008-02-01

    The relationship between acetylcholinesterase (AChE) activity in the CSF and brain of patients with Alzheimer's disease (AD) was investigated in 18 mild AD patients following galantamine treatment. The first 3 months of the study had a randomized double-blind placebo-controlled design, during which 12 patients received galantamine (16-24 mg/day) and six patients placebo. This was followed by 9 months galantamine treatment in all patients. Activities and protein levels of both the "read-through" AChE (AChE-R) and the synaptic (AChE-S) variants in CSF were assessed in parallel together with the regional brain AChE activity by (11)C-PMP and PET. The AChE-S inhibition was 30-36% in CSF, which correlated well with the in vivo AChE inhibition in the brain. No significant AChE inhibition was observed in the placebo group. The increased level of the AChE-R protein was 16% higher than that of AChE-S. Both the AChE inhibition and the increased level of AChE-R protein positively correlated with the patient's performance in cognitive tests associated with visuospatial ability and attention. In conclusion, AChE levels in CSF closely mirror in vivo brain AChE levels prior to and after treatment with the cholinesterase inhibitors. A positive cognitive response seems to dependent on the AChE inhibition level, which is balanced by an increased protein level of the AChE-R variant in the patients.

  7. Structural brain development between childhood and adulthood: Convergence across four longitudinal samples.

    PubMed

    Mills, Kathryn L; Goddings, Anne-Lise; Herting, Megan M; Meuwese, Rosa; Blakemore, Sarah-Jayne; Crone, Eveline A; Dahl, Ronald E; Güroğlu, Berna; Raznahan, Armin; Sowell, Elizabeth R; Tamnes, Christian K

    2016-11-01

    Longitudinal studies including brain measures acquired through magnetic resonance imaging (MRI) have enabled population models of human brain development, crucial for our understanding of typical development as well as neurodevelopmental disorders. Brain development in the first two decades generally involves early cortical grey matter volume (CGMV) increases followed by decreases, and monotonic increases in cerebral white matter volume (CWMV). However, inconsistencies regarding the precise developmental trajectories call into question the comparability of samples. This issue can be addressed by conducting a comprehensive study across multiple datasets from diverse populations. Here, we present replicable models for gross structural brain development between childhood and adulthood (ages 8-30years) by repeating analyses in four separate longitudinal samples (391 participants; 852 scans). In addition, we address how accounting for global measures of cranial/brain size affect these developmental trajectories. First, we found evidence for continued development of both intracranial volume (ICV) and whole brain volume (WBV) through adolescence, albeit following distinct trajectories. Second, our results indicate that CGMV is at its highest in childhood, decreasing steadily through the second decade with deceleration in the third decade, while CWMV increases until mid-to-late adolescence before decelerating. Importantly, we show that accounting for cranial/brain size affects models of regional brain development, particularly with respect to sex differences. Our results increase confidence in our knowledge of the pattern of brain changes during adolescence, reduce concerns about discrepancies across samples, and suggest some best practices for statistical control of cranial volume and brain size in future studies.

  8. Using Structural Equation Modeling to Assess Functional Connectivity in the Brain: Power and Sample Size Considerations

    ERIC Educational Resources Information Center

    Sideridis, Georgios; Simos, Panagiotis; Papanicolaou, Andrew; Fletcher, Jack

    2014-01-01

    The present study assessed the impact of sample size on the power and fit of structural equation modeling applied to functional brain connectivity hypotheses. The data consisted of time-constrained minimum norm estimates of regional brain activity during performance of a reading task obtained with magnetoencephalography. Power analysis was first…

  9. [Application of over sampling sigma-delta A/D in DOAS system].

    PubMed

    Li, Su-wen; Liu, Wen-qing; Xie, Pin-hua

    2006-12-01

    Differential optical absorption spectroscopy (DOAS) has become a widely used method to measure trace gases in the atmosphere. Concentration of trace gases is retrieved using least-squares fits of reference spectra to the measurement spectra. The measurement precision not only depends on the measurement precision of spectra and the noise of instrument and disturbing of other gases in measuring band, but suffers the influence of signal sampling and pre-processing. The present paper simply introduced DOAS measuring principle and the setup of instrument and put forward improving method-the technology of over sampling sigma- deltaA/D. Using the sigma-delta modulator structure to shape noises together with the over sampling technology can doubly restrain quantifying noises, which can improve the signal-to-noise ratio within the measuring band. So the measurement precision of DOAS system is improved with this technology. PMID:17361733

  10. MSL's Widgets: Adding Rebustness to Martian Sample Acquisition, Handling, and Processing

    NASA Technical Reports Server (NTRS)

    Roumeliotis, Chris; Kennedy, Brett; Lin, Justin; DeGrosse, Patrick; Cady, Ian; Onufer, Nicholas; Sigel, Deborah; Jandura, Louise; Anderson, Robert; Katz, Ira; Slimko, Eric; Limonadi, Daniel

    2013-01-01

    Mars Science Laboratory's (MSL) Sample Acquisition Sample Processing and Handling (SA-SPaH) system is one of the most ambitious terrain interaction and manipulation systems ever built and successfully used outside of planet earth. Mars has a ruthless environment that has surprised many who have tried to explore there. The robustness widget program was implemented by the MSL project to help ensure the SA-SPaH system would be robust enough to the surprises of this ruthless Martian environment. The robustness widget program was an effort of extreme schedule pressure and responsibility, but was accomplished with resounding success. This paper will focus on a behind the scenes look at MSL's robustness widgets: the particle fun zone, the wind guards, and the portioner pokers.

  11. Brain imaging of cognitively normal individuals with 2 parents affected by late-onset AD

    PubMed Central

    Murray, John; Tsui, Wai H.; Spector, Nicole; Goldowsky, Alexander; Williams, Schantel; Osorio, Ricardo; McHugh, Pauline; Glodzik, Lidia; Vallabhajosula, Shankar; de Leon, Mony J.

    2014-01-01

    Objectives: This brain imaging study examines whether cognitively normal (NL) individuals with 2 parents affected by late-onset Alzheimer disease (LOAD) show evidence of more extensive Alzheimer disease pathology compared with those who have a single parent affected by LOAD. Methods: Fifty-two NL individuals received MRI, 11C-Pittsburgh compound B (PiB)-PET, and 18F-fluoro-2-deoxyglucose (FDG)-PET. These included 4 demographically balanced groups (n = 13/group, aged 32–72 years, 60% female, 30% APOE ε4 carriers) of NL individuals with maternal (FHm), paternal (FHp), and maternal and paternal (FHmp) family history of LOAD, and with negative family history (FH−). Statistical parametric mapping, voxel-based morphometry, and z-score mapping were used to compare MRI gray matter volumes (GMVs), partial volume–corrected PiB retention, and FDG metabolism across FH groups and vs FH−. Results: NL FHmp showed more severe abnormalities in all 3 biomarkers vs the other groups regarding the number of regions affected and magnitude of impairment. PiB retention and hypometabolism were most pronounced in FHmp, intermediate in FHm, and lowest in FHp and FH−. GMV reductions were highest in FHmp and intermediate in FHm and FHp vs FH−. In all FH+ groups, amyloid-β deposition exceeded GMV loss and hypometabolism exceeded GMV loss (p < 0.001), while amyloid-β deposition exceeded hypometabolism in FHmp and FHp but not in FHm. Conclusions: These biomarker findings show a “LOAD parent-dose effect” in NL individuals several years, if not decades, before possible clinical symptoms. PMID:24523481

  12. The added value of ordinal analysis in clinical trials: an example in traumatic brain injury

    PubMed Central

    2011-01-01

    Introduction In clinical trials, ordinal outcome measures are often dichotomized into two categories. In traumatic brain injury (TBI) the 5-point Glasgow outcome scale (GOS) is collapsed into unfavourable versus favourable outcome. Simulation studies have shown that exploiting the ordinal nature of the GOS increases chances of detecting treatment effects. The objective of this study is to quantify the benefits of ordinal analysis in the real-life situation of a large TBI trial. Methods We used data from the CRASH trial that investigated the efficacy of corticosteroids in TBI patients (n = 9,554). We applied two techniques for ordinal analysis: proportional odds analysis and the sliding dichotomy approach, where the GOS is dichotomized at different cut-offs according to baseline prognostic risk. These approaches were compared to dichotomous analysis. The information density in each analysis was indicated by a Wald statistic. All analyses were adjusted for baseline characteristics. Results Dichotomous analysis of the six-month GOS showed a non-significant treatment effect (OR = 1.09, 95% CI 0.98 to 1.21, P = 0.096). Ordinal analysis with proportional odds regression or sliding dichotomy showed highly statistically significant treatment effects (OR 1.15, 95% CI 1.06 to 1.25, P = 0.0007 and 1.19, 95% CI 1.08 to 1.30, P = 0.0002), with 2.05-fold and 2.56-fold higher information density compared to the dichotomous approach respectively. Conclusions Analysis of the CRASH trial data confirmed that ordinal analysis of outcome substantially increases statistical power. We expect these results to hold for other fields of critical care medicine that use ordinal outcome measures and recommend that future trials adopt ordinal analyses. This will permit detection of smaller treatment effects. PMID:21586148

  13. Structural brain development between childhood and adulthood: Convergence across four longitudinal samples.

    PubMed

    Mills, Kathryn L; Goddings, Anne-Lise; Herting, Megan M; Meuwese, Rosa; Blakemore, Sarah-Jayne; Crone, Eveline A; Dahl, Ronald E; Güroğlu, Berna; Raznahan, Armin; Sowell, Elizabeth R; Tamnes, Christian K

    2016-11-01

    Longitudinal studies including brain measures acquired through magnetic resonance imaging (MRI) have enabled population models of human brain development, crucial for our understanding of typical development as well as neurodevelopmental disorders. Brain development in the first two decades generally involves early cortical grey matter volume (CGMV) increases followed by decreases, and monotonic increases in cerebral white matter volume (CWMV). However, inconsistencies regarding the precise developmental trajectories call into question the comparability of samples. This issue can be addressed by conducting a comprehensive study across multiple datasets from diverse populations. Here, we present replicable models for gross structural brain development between childhood and adulthood (ages 8-30years) by repeating analyses in four separate longitudinal samples (391 participants; 852 scans). In addition, we address how accounting for global measures of cranial/brain size affect these developmental trajectories. First, we found evidence for continued development of both intracranial volume (ICV) and whole brain volume (WBV) through adolescence, albeit following distinct trajectories. Second, our results indicate that CGMV is at its highest in childhood, decreasing steadily through the second decade with deceleration in the third decade, while CWMV increases until mid-to-late adolescence before decelerating. Importantly, we show that accounting for cranial/brain size affects models of regional brain development, particularly with respect to sex differences. Our results increase confidence in our knowledge of the pattern of brain changes during adolescence, reduce concerns about discrepancies across samples, and suggest some best practices for statistical control of cranial volume and brain size in future studies. PMID:27453157

  14. Lack of leptin activity in blood samples of Adélie penguin and bar-tailed godwit.

    PubMed

    Yosefi, Sara; Hen, Gideon; Rosenblum, Charles I; Cerasale, David J; Beaulieu, Michaël; Criscuolo, Francois; Friedman-Einat, Miriam

    2010-10-01

    Unsuccessful attempts to identify the leptin gene in birds are well documented, despite the characterization of its receptor (LEPR). Since leptin and LEPR have poor sequence conservation among vertebrates, we speculated that a functional assay should represent the best way to detect leptin in birds. Using a leptin bioassay that is based on activation of the chicken LEPR in cultured cells, blood samples from wild birds with extreme seasonal variation in voluntary food intake and fat deposition (Adélie penguins and bar-tailed godwits) were tested for leptin activity. In these experiments, blood samples collected during the pre-incubation and the chick-rearing periods of Adélie penguins, and during the migratory flight and refueling stages of bar-tailed godwits, were found to contain no detectable leptin activity, while the sensitivity of the assay to activation by human blood samples from donor subjects representing a variety of body mass indices and fat contents was clearly demonstrated. These results suggest that in birds, an alternative control mechanism to that of mammals operates in the communication between the body fat tissues and the central control on energy homeostasis.

  15. Mitochondrial Respiration Chain Enzymatic Activities in the Human Brain: Methodological Implications for Tissue Sampling and Storage.

    PubMed

    Ronsoni, Marcelo Fernando; Remor, Aline Pertile; Lopes, Mark William; Hohl, Alexandre; Troncoso, Iris H Z; Leal, Rodrigo Bainy; Boos, Gustavo Luchi; Kondageski, Charles; Nunes, Jean Costa; Linhares, Marcelo Neves; Lin, Kátia; Latini, Alexandra Susana; Walz, Roger

    2016-04-01

    Mitochondrial respiratory chain complexes enzymatic (MRCCE) activities were successfully evaluated in frozen brain samples. Epilepsy surgery offers an ethical opportunity to study human brain tissue surgically removed to treat drug resistant epilepsies. Epilepsy surgeries are done with hemodynamic and laboratory parameters to maintain physiology, but there are no studies analyzing the association among these parameters and MRCCE activities in the human brain tissue. We determined the intra-operative parameters independently associated with MRCCE activities in middle temporal neocortex (Cx), amygdala (AMY) and head of hippocampus (HIP) samples of patients (n = 23) who underwent temporal lobectomy using multiple linear regressions. MRCCE activities in Cx, AMY and HIP are differentially associated to trans-operative mean arterial blood pressure, O2 saturation, hemoglobin, and anesthesia duration to time of tissue sampling. The time-course between the last seizure occurrence and tissue sampling as well as the sample storage to biochemical assessments were also associated with enzyme activities. Linear regression models including these variables explain 13-17 % of MRCCE activities and show a moderate to strong effect (r = 0.37-0.82). Intraoperative hemodynamic and laboratory parameters as well as the time from last seizure to tissue sampling and storage time are associated with MRCCE activities in human samples from the Cx, AMYG and HIP. Careful control of these parameters is required to minimize confounding biases in studies using human brain samples collected from elective neurosurgery. PMID:26586405

  16. Using psychophysics to ask if the brain samples or maximizes

    PubMed Central

    Acuna, Daniel E.; Berniker, Max; Fernandes, Hugo L.; Kording, Konrad P.

    2015-01-01

    The two-alternative forced-choice (2AFC) task is the workhorse of psychophysics and is used to measure the just-noticeable difference, generally assumed to accurately quantify sensory precision. However, this assumption is not true for all mechanisms of decision making. Here we derive the behavioral predictions for two popular mechanisms, sampling and maximum a posteriori, and examine how they affect the outcome of the 2AFC task. These predictions are used in a combined visual 2AFC and estimation experiment. Our results strongly suggest that subjects use a maximum a posteriori mechanism. Further, our derivations and experimental paradigm establish the already standard 2AFC task as a behavioral tool for measuring how humans make decisions under uncertainty. PMID:25767093

  17. Sample sizes for brain atrophy outcomes in trials for secondary progressive multiple sclerosis

    PubMed Central

    Altmann, D R.; Jasperse, B; Barkhof, F; Beckmann, K; Filippi, M; Kappos, L D.; Molyneux, P; Polman, C H.; Pozzilli, C; Thompson, A J.; Wagner, K; Yousry, T A.; Miller, D H.

    2009-01-01

    Background: Progressive brain atrophy in multiple sclerosis (MS) may reflect neuroaxonal and myelin loss and MRI measures of brain tissue loss are used as outcome measures in MS treatment trials. This study investigated sample sizes required to demonstrate reduction of brain atrophy using three outcome measures in a parallel group, placebo-controlled trial for secondary progressive MS (SPMS). Methods: Data were taken from a cohort of 43 patients with SPMS who had been followed up with 6-monthly T1-weighted MRI for up to 3 years within the placebo arm of a therapeutic trial. Central cerebral volumes (CCVs) were measured using a semiautomated segmentation approach, and brain volume normalized for skull size (NBV) was measured using automated segmentation (SIENAX). Change in CCV and NBV was measured by subtraction of baseline from serial CCV and SIENAX images; in addition, percentage brain volume change relative to baseline was measured directly using a registration-based method (SIENA). Sample sizes for given treatment effects and power were calculated for standard analyses using parameters estimated from the sample. Results: For a 2-year trial duration, minimum sample sizes per arm required to detect a 50% treatment effect at 80% power were 32 for SIENA, 69 for CCV, and 273 for SIENAX. Two-year minimum sample sizes were smaller than 1-year by 71% for SIENAX, 55% for CCV, and 44% for SIENA. Conclusion: SIENA and central cerebral volume are feasible outcome measures for inclusion in placebo-controlled trials in secondary progressive multiple sclerosis. GLOSSARY ANCOVA = analysis of covariance; CCV = central cerebral volume; FSL = FMRIB Software Library; MNI = Montreal Neurological Institute; MS = multiple sclerosis; NBV = normalized brain volume; PBVC = percent brain volume change; RRMS = relapsing–remitting multiple sclerosis; SPMS = secondary progressive multiple sclerosis. PMID:19005170

  18. One-step labeling of degenerative neurons in unfixed brain tissue samples using Fluoro-Jade C.

    PubMed

    Gu, Qiang; Schmued, Larry C; Sarkar, Sumit; Paule, Merle G; Raymick, Bryan

    2012-06-30

    Neurodegeneration is the underlying cause of a vast majority of neurological disorders and often a result of brain trauma, stroke, or neurotoxic insult. Here we describe a simple method for labeling degenerating neurons in unfixed brain tissue samples. This method could provide a new avenue for identifying and harvesting degenerative neurons from unfixed brain tissues for subsequent molecular analyses.

  19. Integration and relative value of biomarkers for prediction of MCI to AD progression: spatial patterns of brain atrophy, cognitive scores, APOE genotype and CSF biomarkers.

    PubMed

    Da, Xiao; Toledo, Jon B; Zee, Jarcy; Wolk, David A; Xie, Sharon X; Ou, Yangming; Shacklett, Amanda; Parmpi, Paraskevi; Shaw, Leslie; Trojanowski, John Q; Davatzikos, Christos

    2014-01-01

    This study evaluates the individual, as well as relative and joint value of indices obtained from magnetic resonance imaging (MRI) patterns of brain atrophy (quantified by the SPARE-AD index), cerebrospinal fluid (CSF) biomarkers, APOE genotype, and cognitive performance (ADAS-Cog) in progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD) within a variable follow-up period up to 6 years, using data from the Alzheimer's Disease Neuroimaging Initiative-1 (ADNI-1). SPARE-AD was first established as a highly sensitive and specific MRI-marker of AD vs. cognitively normal (CN) subjects (AUC = 0.98). Baseline predictive values of all aforementioned indices were then compared using survival analysis on 381 MCI subjects. SPARE-AD and ADAS-Cog were found to have similar predictive value, and their combination was significantly better than their individual performance. APOE genotype did not significantly improve prediction, although the combination of SPARE-AD, ADAS-Cog and APOE ε4 provided the highest hazard ratio estimates of 17.8 (last vs. first quartile). In a subset of 192 MCI patients who also had CSF biomarkers, the addition of Aβ1-42, t-tau, and p-tau181p to the previous model did not improve predictive value significantly over SPARE-AD and ADAS-Cog combined. Importantly, in amyloid-negative patients with MCI, SPARE-AD had high predictive power of clinical progression. Our findings suggest that SPARE-AD and ADAS-Cog in combination offer the highest predictive power of conversion from MCI to AD, which is improved, albeit not significantly, by APOE genotype. The finding that SPARE-AD in amyloid-negative MCI patients was predictive of clinical progression is not expected under the amyloid hypothesis and merits further investigation.

  20. In-capillary derivatization and capillary electrophoresis separation of amino acid neurotransmitters from brain microdialysis samples.

    PubMed

    Denoroy, Luc; Parrot, Sandrine; Renaud, Louis; Renaud, Bernard; Zimmer, Luc

    2008-09-26

    A new in-capillary derivatization method with naphtalene-2,3-dicarboxyaldehyde (NDA)/CN(-) has been developed for capillary electrophoresis with laser-induced fluorescence detection of brain microdialysate amino acids. Samples are sandwiched between two plugs of reagent mixture at the capillary inlet and subsequently separated. Highest derivatization yields are obtained by using a reagent to sample plug length ratio equal to 4, performing a first electrophoretic mixing followed by a zero potential amplification step before applying the separation voltage and using a NaCN to NDA concentration ratio equal to 1. This new single-step methodology allows the analysis of amino acid neurotransmitters in rat brain microdialysis samples.

  1. Exenatide promotes cognitive enhancement and positive brain metabolic changes in PS1-KI mice but has no effects in 3xTg-AD animals.

    PubMed

    Bomba, M; Ciavardelli, D; Silvestri, E; Canzoniero, L M T; Lattanzio, R; Chiappini, P; Piantelli, M; Di Ilio, C; Consoli, A; Sensi, S L

    2013-05-02

    Recent studies have shown that type 2 diabetes mellitus (T2DM) is a risk factor for cognitive dysfunction or dementia. Insulin resistance is often associated with T2DM and can induce defective insulin signaling in the central nervous system as well as increase the risk of cognitive impairment in the elderly. Glucagone like peptide-1 (GLP-1) is an incretin hormone and, like GLP-1 analogs, stimulates insulin secretion and has been employed in the treatment of T2DM. GLP-1 and GLP-1 analogs also enhance synaptic plasticity and counteract cognitive deficits in mouse models of neuronal dysfunction and/or degeneration. In this study, we investigated the potential neuroprotective effects of long-term treatment with exenatide, a GLP-1 analog, in two animal models of neuronal dysfunction: the PS1-KI and 3xTg-AD mice. We found that exenatide promoted beneficial effects on short- and long-term memory performances in PS1-KI but not in 3xTg-AD animals. In PS1-KI mice, the drug increased brain lactate dehydrogenase activity leading to a net increase in lactate levels, while no effects were observed on mitochondrial respiration. On the contrary, exenatide had no effects on brain metabolism of 3xTg-AD mice. In summary, our data indicate that exenatide improves cognition in PS1-KI mice, an effect likely driven by increasing the brain anaerobic glycolysis rate.

  2. Exenatide promotes cognitive enhancement and positive brain metabolic changes in PS1-KI mice but has no effects in 3xTg-AD animals

    PubMed Central

    Bomba, M; Ciavardelli, D; Silvestri, E; Canzoniero, L MT; Lattanzio, R; Chiappini, P; Piantelli, M; Di Ilio, C; Consoli, A; Sensi, S L

    2013-01-01

    Recent studies have shown that type 2 diabetes mellitus (T2DM) is a risk factor for cognitive dysfunction or dementia. Insulin resistance is often associated with T2DM and can induce defective insulin signaling in the central nervous system as well as increase the risk of cognitive impairment in the elderly. Glucagone like peptide-1 (GLP-1) is an incretin hormone and, like GLP-1 analogs, stimulates insulin secretion and has been employed in the treatment of T2DM. GLP-1 and GLP-1 analogs also enhance synaptic plasticity and counteract cognitive deficits in mouse models of neuronal dysfunction and/or degeneration. In this study, we investigated the potential neuroprotective effects of long-term treatment with exenatide, a GLP-1 analog, in two animal models of neuronal dysfunction: the PS1-KI and 3xTg-AD mice. We found that exenatide promoted beneficial effects on short- and long-term memory performances in PS1-KI but not in 3xTg-AD animals. In PS1-KI mice, the drug increased brain lactate dehydrogenase activity leading to a net increase in lactate levels, while no effects were observed on mitochondrial respiration. On the contrary, exenatide had no effects on brain metabolism of 3xTg-AD mice. In summary, our data indicate that exenatide improves cognition in PS1-KI mice, an effect likely driven by increasing the brain anaerobic glycolysis rate. PMID:23640454

  3. Freeze-Drying as Sample Preparation for Micellar Electrokinetic Capillary Chromatography – Electrochemical Separations of Neurochemicals in Drosophila Brains

    PubMed Central

    Berglund, E. Carina; Kuklinski, Nicholas J.; Karagündüz, Ekin; Ucar, Kubra; Hanrieder, Jörg; Ewing, Andrew G.

    2013-01-01

    Micellar electrokinetic capillary chromatography with electrochemical detection has been used to quantify biogenic amines in freeze-dried Drosophila melanogaster brains. Freeze drying samples offers a way to preserve the biological sample while making dissection of these tiny samples easier and faster. Fly samples were extracted in cold acetone and dried in a rotary evaporator. Extraction and drying times were optimized in order to avoid contamination by red-pigment from the fly eyes and still have intact brain structures. Single freeze-dried fly-brain samples were found to produce representative electropherograms as a single hand-dissected brain sample. Utilizing the faster dissection time that freeze drying affords, the number of brains in a fixed homogenate volume can be increased to concentrate the sample. Thus, concentrated brain samples containing five or fifteen preserved brains were analyzed for their neurotransmitter content, and five analytes; dopamine N-acetyloctopamine, Nacetylserotonin, N-acetyltyramine, N-acetyldopamine were found to correspond well with previously reported values. PMID:23387977

  4. Brain

    MedlinePlus

    ... will return after updating. Resources Archived Modules Updates Brain Cerebrum The cerebrum is the part of the ... the outside of the brain and spinal cord. Brain Stem The brain stem is the part of ...

  5. Analysis of glutathione levels in the brain tissue samples from HIV-1-positive individuals and subject with Alzheimer's disease and its implication in the pathophysiology of the disease process.

    PubMed

    Saing, Tommy; Lagman, Minette; Castrillon, Jeffery; Gutierrez, Eutiquio; Guilford, Frederick T; Venketaraman, Vishwanath

    2016-12-01

    HIV-1 positive individuals are at high risk for susceptibility to both pulmonary tuberculosis (TB) and extra-pulmonary TB, including TB meningitis (TBM) which is an extreme form of TB. The goals of this study are to determine the mechanisms responsible for compromised levels of glutathione (GSH) in the brain tissue samples derived from HIV-1-infected individuals and individuals with Alzheimer's disease (AD), investigate the possible underlying mechanisms responsible for GSH deficiency in these pathological conditions, and establish a link between GSH levels and pathophysiology of the disease processes. We demonstrated in the autopsied human brain tissues that the levels of total and reduced forms of GSH were significantly compromised in HIV-1 infected individuals compared to in healthy subjects and individuals with AD. Brain tissue samples derived from HIV-1-positive individuals had substantially higher levels of free radicals than that derived from healthy and AD individuals. Enzymes that are responsible for the de novo synthesis of GSH such as γ-glutamate cysteine-ligase catalytic subunit (GCLC-rate limiting step enzyme) and glutathione synthetase (GSS-enzyme involved in the second step reaction) were significantly decreased in the brain tissue samples derived from HIV-1-positive individuals with low CD4 + T-cells (< 200 cells/mm(3)) compared to healthy and AD individuals. Levels of glutathione reductase (GSR) were also decreased in the brain tissue samples derived from HIV-1 infected individuals. Overall, our findings demonstrate causes for GSH deficiency in the brain tissue from HIV-1 infected individuals explaining the possible reasons for increased susceptibility to the most severe form of extra-pulmonary TB, TBM. PMID:27335804

  6. 5-Lipoxygenase gene transfer worsens memory, amyloid and tau brain pathologies in a mouse model of AD

    PubMed Central

    Chu, Jin; Giannopoulos, Phillip F.; Ceballos-Diaz, Carolina; Golde, Todd E.; Pratico, Domenico

    2012-01-01

    Objective The 5-lipoxygenase (5LO) enzyme is up-regulated in Alzheimer’s disease (AD), and its genetic absence reduces Aβ levels in APP mice. However, its functional role in modulating tau neuropathology remains to be elucidated. Methods To this end, we generated triple transgenic mice (3xTg-AD) over-expressing neuronal 5LO and investigated their phenotype. Results Compared with controls, 3xTg-AD mice over-expressing 5LO manifested an exacerbation of memory deficits, plaques and tangles pathologies. The elevation in Aβ was secondary to an up-regulation of γ-secretase pathway, whereas tau hyperphosphorylation resulted from an activation of the Cdk5 kinase. In vitro study confirmed the involvement of this kinase in the 5-LO-dependent tau phosphorylation, which was independent of the effect on Aβ. Interpretation Our findings highlight the novel functional role that neuronal 5LO plays in exacerbating AD-related tau pathologies. They provide critical preclinical evidence to justify testing selective 5LO inhibitors for AD treatment. PMID:23034916

  7. Whole genome association study of brain-wide imaging phenotypes for identifying quantitative trait loci in MCI and AD: A study of the ADNI cohort.

    PubMed

    Shen, Li; Kim, Sungeun; Risacher, Shannon L; Nho, Kwangsik; Swaminathan, Shanker; West, John D; Foroud, Tatiana; Pankratz, Nathan; Moore, Jason H; Sloan, Chantel D; Huentelman, Matthew J; Craig, David W; Dechairo, Bryan M; Potkin, Steven G; Jack, Clifford R; Weiner, Michael W; Saykin, Andrew J

    2010-11-15

    A genome-wide, whole brain approach to investigate genetic effects on neuroimaging phenotypes for identifying quantitative trait loci is described. The Alzheimer's Disease Neuroimaging Initiative 1.5 T MRI and genetic dataset was investigated using voxel-based morphometry (VBM) and FreeSurfer parcellation followed by genome-wide association studies (GWAS). One hundred forty-two measures of grey matter (GM) density, volume, and cortical thickness were extracted from baseline scans. GWAS, using PLINK, were performed on each phenotype using quality-controlled genotype and scan data including 530,992 of 620,903 single nucleotide polymorphisms (SNPs) and 733 of 818 participants (175 AD, 354 amnestic mild cognitive impairment, MCI, and 204 healthy controls, HC). Hierarchical clustering and heat maps were used to analyze the GWAS results and associations are reported at two significance thresholds (p<10(-7) and p<10(-6)). As expected, SNPs in the APOE and TOMM40 genes were confirmed as markers strongly associated with multiple brain regions. Other top SNPs were proximal to the EPHA4, TP63 and NXPH1 genes. Detailed image analyses of rs6463843 (flanking NXPH1) revealed reduced global and regional GM density across diagnostic groups in TT relative to GG homozygotes. Interaction analysis indicated that AD patients homozygous for the T allele showed differential vulnerability to right hippocampal GM density loss. NXPH1 codes for a protein implicated in promotion of adhesion between dendrites and axons, a key factor in synaptic integrity, the loss of which is a hallmark of AD. A genome-wide, whole brain search strategy has the potential to reveal novel candidate genes and loci warranting further investigation and replication.

  8. Ex vivo confocal microscopy imaging to identify tumor tissue on freshly removed brain sample.

    PubMed

    Forest, Fabien; Cinotti, Elisa; Yvorel, Violaine; Habougit, Cyril; Vassal, François; Nuti, Christophe; Perrot, Jean-Luc; Labeille, Bruno; Péoc'h, Michel

    2015-09-01

    Confocal microscopy is a technique able to realize "optic sections" of a tissue with increasing applications. We wondered if we could apply an ex vivo confocal microscope designed for dermatological purpose in a routine use for the most frequent brain tumors. The aim of this work was to identify tumor tissue and its histopathological hallmarks, and to assess grading criteria used in neuropathological practice without tissue loss on freshly removed brain tissue. Seven infiltrating gliomas, nine meningiomas and three metastases of carcinomas were included. We compared imaging results obtained with the confocal microscope to frozen sections, smears and tissue sections of formalin-fixed tissue. Our results show that ex vivo confocal microscopy imaging can be applied to brain tumors in order to quickly identify tumor tissue without tissue loss. It can differentiate tumors and can assess most of grading criteria. Confocal microscopy could represent a new tool to identify tumor tissue on freshly removed sample and could help in selecting areas for biobanking of tumor tissue.

  9. Increased brain uptake of targeted nanoparticles by adding an acid-cleavable linkage between transferrin and the nanoparticle core.

    PubMed

    Clark, Andrew J; Davis, Mark E

    2015-10-01

    Most therapeutic agents are excluded from entering the central nervous system by the blood-brain barrier (BBB). Receptor mediated transcytosis (RMT) is a common mechanism used by proteins, including transferrin (Tf), to traverse the BBB. Here, we prepared Tf-containing, 80-nm gold nanoparticles with an acid-cleavable linkage between the Tf and the nanoparticle core to facilitate nanoparticle RMT across the BBB. These nanoparticles are designed to bind to Tf receptors (TfRs) with high avidity on the blood side of the BBB, but separate from their multidentate Tf-TfR interactions upon acidification during the transcytosis process to allow release of the nanoparticle into the brain. These targeted nanoparticles show increased ability to cross an in vitro model of the BBB and, most important, enter the brain parenchyma of mice in greater amounts in vivo after systemic administration compared with similar high-avidity nanoparticles containing noncleavable Tf. In addition, we investigated this design with nanoparticles containing high-affinity antibodies (Abs) to TfR. With the Abs, the addition of the acid-cleavable linkage provided no improvement to in vivo brain uptake for Ab-containing nanoparticles, and overall brain uptake was decreased for all Ab-containing nanoparticles compared with Tf-containing ones. These results are consistent with recent reports of high-affinity anti-TfR Abs trafficking to the lysosome within BBB endothelium. In contrast, high-avidity, Tf-containing nanoparticles with the acid-cleavable linkage avoid major endothelium retention by shedding surface Tf during their transcytosis. PMID:26392563

  10. Increased brain uptake of targeted nanoparticles by adding an acid-cleavable linkage between transferrin and the nanoparticle core.

    PubMed

    Clark, Andrew J; Davis, Mark E

    2015-10-01

    Most therapeutic agents are excluded from entering the central nervous system by the blood-brain barrier (BBB). Receptor mediated transcytosis (RMT) is a common mechanism used by proteins, including transferrin (Tf), to traverse the BBB. Here, we prepared Tf-containing, 80-nm gold nanoparticles with an acid-cleavable linkage between the Tf and the nanoparticle core to facilitate nanoparticle RMT across the BBB. These nanoparticles are designed to bind to Tf receptors (TfRs) with high avidity on the blood side of the BBB, but separate from their multidentate Tf-TfR interactions upon acidification during the transcytosis process to allow release of the nanoparticle into the brain. These targeted nanoparticles show increased ability to cross an in vitro model of the BBB and, most important, enter the brain parenchyma of mice in greater amounts in vivo after systemic administration compared with similar high-avidity nanoparticles containing noncleavable Tf. In addition, we investigated this design with nanoparticles containing high-affinity antibodies (Abs) to TfR. With the Abs, the addition of the acid-cleavable linkage provided no improvement to in vivo brain uptake for Ab-containing nanoparticles, and overall brain uptake was decreased for all Ab-containing nanoparticles compared with Tf-containing ones. These results are consistent with recent reports of high-affinity anti-TfR Abs trafficking to the lysosome within BBB endothelium. In contrast, high-avidity, Tf-containing nanoparticles with the acid-cleavable linkage avoid major endothelium retention by shedding surface Tf during their transcytosis.

  11. Stereotactic radiosurgery as therapy for melanoma, renal carcinoma, and sarcoma brain metastases: Impact of added surgical resection and whole-brain radiotherapy

    SciTech Connect

    Rao, Ganesh; Klimo, Paul; Thompson, Clinton J.; Samlowski, Wolfram; Wang, Michael; Watson, Gordon; Shrieve, Dennis; Jensen, Randy L. . E-mail: randy.jensen@hsc.utah.edu

    2006-11-15

    Purpose: Brain metastases of melanoma, renal carcinoma, and sarcoma have traditionally responded poorly to conventional treatments, including surgery and whole-brain radiotherapy (WBRT). Several studies have suggested a beneficial effect of stereotactic radiosurgery (SRS). We evaluated our institutional experience with systematic SRS in patients harboring these 'radioresistant' metastases. Methods and Materials: A total of 68 patients with brain metastases from melanoma, renal carcinoma, and sarcoma underwent SRS with or without WBRT or surgical resection. All patients had Karnofsky performance scores >70, and SRS was performed before the initiation of systemic therapy. The survival time was calculated from the diagnosis of brain metastases using the Kaplan-Meier product-limit method. Statistical significance was calculated using the log-rank test. Factors influencing survival, including surgical resection, WBRT, gender, number of SRS sessions, and histologic type, were evaluated retrospectively using Cox univariate models. Results: The overall median survival was 427 days (14.2 months), which appears superior to the results obtained with conventional WBRT. The addition of neither surgery nor WBRT to SRS provided a statistically significant increase in survival. Conclusion: Our results suggest that patients undergoing SRS for up to five cerebral metastases from 'radioresistant' tumors (melanoma, renal cell carcinoma, and sarcoma) have survival rates comparable to those in other series of more selected patients. The addition of surgical resection or WBRT did not result in improved survival in our series.

  12. Frontiers for the Early Diagnosis of AD by Means of MRI Brain Imaging and Support Vector Machines.

    PubMed

    Salvatore, Christian; Battista, Petronilla; Castiglioni, Isabella

    2016-01-01

    The emergence of Alzheimer's Disease (AD) as a consequence of increasing aging population makes urgent the availability of methods for the early and accurate diagnosis. Magnetic Resonance Imaging (MRI) could be used as in vivo, non invasive tool to identify sensitive and specific markers of very early AD progression. In recent years, multivariate pattern analysis (MVPA) and machine- learning algorithms have attracted strong interest within the neuroimaging community, as they allow automatic classification of imaging data with higher performance than univariate statistical analysis. An exhaustive search of PubMed, Web of Science and Medline records was performed in this work, in order to retrieve studies focused on the potential role of MRI in aiding the clinician in early diagnosis of AD by using Support Vector Machines (SVMs) as MVPA automated classification method. A total of 30 studies emerged, published from 2008 to date. This review aims to give a state-of-the-art overview about SVM for the early and differential diagnosis of AD-related pathologies by means of MRI data, starting from preliminary steps such as image pre-processing, feature extraction and feature selection, and ending with classification, validation strategies and extraction of MRI-related biomarkers. The main advantages and drawbacks of the different techniques were explored. Results obtained by the reviewed studies were reported in terms of classification performance and biomarker outcomes, in order to shed light on the parameters that accompany normal and pathological aging. Unresolved issues and possible future directions were finally pointed out. PMID:26567735

  13. Synchronous Multiscale Neuroimaging Environment for Critically Sampled Physiological Analysis of Brain Function: Hepta-Scan Concept

    PubMed Central

    Korhonen, Vesa; Hiltunen, Tuija; Myllylä, Teemu; Wang, Xindi; Kantola, Jussi; Nikkinen, Juha; Zang, Yu-Feng; LeVan, Pierre

    2014-01-01

    Abstract Functional connectivity of the resting-state networks of the brain is thought to be mediated by very-low-frequency fluctuations (VLFFs <0.1 Hz) in neuronal activity. However, vasomotor waves and cardiorespiratory pulsations influence indirect measures of brain function, such as the functional magnetic resonance imaging blood-oxygen-level-dependent (BOLD) signal. How strongly physiological oscillations correlate with spontaneous BOLD signals is not known, partially due to differences in the data-sampling rates of different methods. Recent ultrafast inverse imaging sequences, including magnetic resonance encephalography (MREG), enable critical sampling of these signals. In this study, we describe a multimodal concept, referred to as Hepta-scan, which incorporates synchronous MREG with scalp electroencephalography, near-infrared spectroscopy, noninvasive blood pressure, and anesthesia monitoring. Our preliminary results support the idea that, in the absence of aliased cardiorespiratory signals, VLFFs in the BOLD signal are affected by vasomotor and electrophysiological sources. Further, MREG signals showed a high correlation coefficient between the ventromedial default mode network (DMNvmpf) and electrophysiological signals, especially in the VLF range. Also, oxy- and deoxyhemoglobin and vasomotor waves were found to correlate with DMNvmpf. Intriguingly, usage of shorter time windows in these correlation measurements produced significantly (p<0.05) higher positive and negative correlation coefficients, suggesting temporal nonstationary behavior between the measurements. Focus on the VLF range strongly increased correlation strength. PMID:25131996

  14. Terahertz spectroscopy and detection of brain tumor in rat fresh-tissue samples

    NASA Astrophysics Data System (ADS)

    Yamaguchi, S.; Fukushi, Y.; Kubota, O.; Itsuji, T.; Yamamoto, S.; Ouchi, T.

    2015-03-01

    Terahertz (THz) spectroscopy and imaging of biomedical samples is expected to be an important application of THz analysis techniques. Identification and localization of tumor tissue, imaging of biological samples, and analysis of DNA by THz spectroscopy have been reported. THz time-domain spectroscopy (TDS) is useful for obtaining the refractive index over a broad frequency range. However, THz-TDS spectra of fresh tissue samples are sensitive to procedures such as sample preparation, and a standardized measurement protocol is required. Therefore, in this work, we establish a protocol for measurements of THz spectra of fresh tissue and demonstrate reliable detection of rat brain tumor tissue. We use a reflection THz-TDS system to measure the refractive index spectra of the samples mounted on a quartz plate. The tissue samples were measured immediately after sectioning to avoid sample denaturalization during storage. Special care was taken in THz data processing to eliminate parasitic reflections and reduce noise. The error level in our refractive index measurements was as low as 0.02 in the frequency range 0.8-1.5 THz. With increasing frequency, the refractive index in the tumor and normal regions monotonically decreased, similarly to water, and it was 0.02 higher in the tumor regions. The spectral data suggest that the tumor regions have higher water content. Hematoxylin-eosin stained images showed that increased cell density was also responsible for the observed spectral features. A set of samples from 10 rats showed consistent results. Our results suggest that reliable tumor detection in fresh tissue without pretreatment is possible with THz spectroscopy measurements. THz spectroscopy has the potential to become a real-time in vivo diagnostic method.

  15. The relationship between decorrelation time and sample thickness in acute rat brain tissue slices (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Brake, Joshua; Jang, Mooseok; Yang, Changhuei

    2016-03-01

    The optical opacity of biological tissue has long been a challenge in biomedical optics due to the strong scattering nature of tissue in the optical regime. While most conventional optical techniques attempt to gate out multiply scattered light and use only unscattered light, new approaches in the field of wavefront shaping exploit the time reversible symmetry of optical scattering in order to focus light inside or through scattering media. While these approaches have been demonstrated effectively on static samples, it has proven difficult to apply them to dynamic biological samples since even small changes in the relative positions of the scatterers within will cause the time symmetry that wavefront shaping relies upon to decorrelate. In this paper we investigate the decorrelation curves of acute rat brain slices for thicknesses in the range 1-3 mm (1/e decorrelation time on the order of seconds) using multi-speckle diffusing wave spectroscopy (MSDWS) and compare the results with theoretical predictions. The results of this study demonstrate that the 1/L^2 relationship between decorrelation time and thickness predicted by diffusing wave spectroscopy provides a good rule of thumb for estimating how the decorrelation of a sample will change with increasing thickness. Understanding this relationship will provide insight to guide the future development of biophotonic wavefront shaping tools by giving an estimate of how fast wavefront shaping systems need to operate to overcome the dynamic nature of biological samples.

  16. Early alterations in blood and brain RANTES and MCP-1 expression and the effect of exercise frequency in the 3xTg-AD mouse model of Alzheimer's disease.

    PubMed

    Haskins, Morgan; Jones, Terry E; Lu, Qun; Bareiss, Sonja K

    2016-01-01

    Exercise has been shown to protect against cognitive decline and Alzheimer's disease (AD) progression, however the dose of exercise required to protect against AD is unknown. Recent studies show that the pathological processes leading to AD cause characteristic alterations in blood and brain inflammatory proteins that are associated with the progression of AD, suggesting that these markers could be used to diagnosis and monitor disease progression. The purpose of this study was to determine the impact of exercise frequency on AD blood chemokine profiles, and correlate these findings with chemokine brain expression changes in the triple transgenic AD (3xTg-AD) mouse model. Three month old 3xTg-AD mice were subjected to 12 weeks of moderate intensity wheel running at a frequency of either 1×/week or 3×/week. Blood and cortical tissue were analyzed for expression of monocyte chemotactic protein-1 (MCP-1) and regulated and normal T cell expressed and secreted (RANTES). Alterations in blood RANTES and MCP-1 expression were evident at 3 and 6 month old animals compared to WT animals. Three times per week exercise but not 1×/week exercise was effective at reversing serum and brain RANTES and MCP-1 expression to the levels of WT controls, revealing a dose dependent response to exercise. Analysis of these chemokines showed a strong negative correlation between blood and brain expression of RANTES. The results indicate that alterations in serum and brain inflammatory chemokines are evident as early signs of Alzheimer's disease pathology and that higher frequency exercise was necessary to restore blood and brain inflammatory expression levels in this AD mouse model.

  17. [Late-onset Neurodegenerative Diseases Following Traumatic Brain Injury: Chronic Traumatic Encephalopathy (CTE) and Alzheimer's Disease Secondary to TBI (AD-TBI)].

    PubMed

    Takahata, Keisuke; Tabuchi, Hajime; Mimura, Masaru

    2016-07-01

    Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease, which is associated with mild repetitive traumatic brain injury (TBI). This long-term and progressive symptom due to TBI was initially called punch-drunk syndrome or dementia pugilistica, since it was believed to be associated with boxing. However, serial neuropathological studies of mild repetitive TBI in the last decade have revealed that CTE occurs not only in boxers but also in a wider population including American football players, wrestlers, and military personnel. CTE has gained large public interest owing to dramatic cases involving retired professional athletes wherein serious behavioral problems and tragic incidents were reported. Unlike mild repetitive TBI, a single episode of severe TBI can cause another type of late-onset neuropsychiatric disease including Alzheimer's disease (AD). Several epidemiological studies have shown that a single episode of severe TBI is one of the major risk factors of AD. Pathologically, both AD and CTE are characterized by abnormal accumulations of hyperphosphorylated tau proteins. However, recent neuropathological studies revealed that CTE demonstrates a unique pattern of tau pathology in neurons and astrocytes, and accumulation of other misfolded proteins such as TDP-43. Currently, no reliable biomarkers of late-onset neurodegenerative diseases following TBI are available, and a definitive diagnosis can be made only via postmortem neuropathological examination. Development in neuroimaging techniques such as tau and amyloid positron emission tomography imaging might not only enable early diagnosis of CTE, but also contribute to the interventions for prevention of late-onset neurodegenerative diseases following TBI. Further studies are necessary to elucidate the mechanisms of neurodegeneration in the living brain of patients with TBI. PMID:27395469

  18. [Application of solid sampling graphite furnace atomic absorption spectrophotometry to mensuration of brain iron content in rats].

    PubMed

    Zhang, Nan; Sheng, Qing-hai; Shi, Zhen-hua; Zhang, Zhi-guo; Duan, Xiang-lin; Chang, Yan-zhong

    2009-04-01

    In the present study, the authors performed the solid sampling and detected the iron levels in cortex, hippocampus and striatum of rat brain by GFAAS. The authors' results showed that there are no remarkable difference between the data obtained by solid sampling graphite furnace atomic absorption and liquid sampling graphite furnace atomic absorption. Compared to liquid sampling graphite furnace atomic absorption, the sample pre-treatment stage was obviously simplified, the cost was reduced significantly, and the time was shortened significantly in the solid sampling GFAAS. This study will be beneficial to the mensuration of iron content in micro-tissue of animal by solid sampling GFASS.

  19. Age-dependent inverse correlations in CSF and plasma amyloid-β(1–42) concentrations prior to amyloid plaque deposition in the brain of 3xTg-AD mice

    PubMed Central

    Cho, Soo Min; Lee, Sejin; Yang, Seung-Hoon; Kim, Hye Yun; Lee, Michael Jisoo; Kim, Hyunjin Vincent; Kim, Jiyoon; Baek, Seungyeop; Yun, Jin; Kim, Dohee; Kim, Yun Kyung; Cho, Yakdol; Woo, Jiwan; Kim, Tae Song; Kim, YoungSoo

    2016-01-01

    Amyloid-β (Aβ) plays a critical role as a biomarker in Alzheimer’s disease (AD) diagnosis. In addition to its diagnostic potential in the brain, recent studies have suggested that changes of Aβ level in the plasma can possibly indicate AD onset. In this study, we found that plasma Aβ(1–42) concentration increases with age, while the concentration of Aβ(1–42) in the cerebrospinal fluid (CSF) decreases in APPswe, PS1M146V and TauP301L transgenic (3xTg-AD) mice, if measurements were made before formation of ThS-positive plaques in the brain. Our data suggests that there is an inverse correlations between the plasma and CSF Aβ(1–42) levels until plaques form in transgenic mice’s brains and that the plasma Aβ concentration possesses the diagnostic potential as a biomarker for diagnosis of early AD stages. PMID:26830653

  20. Manganese-enhanced magnetic resonance imaging for mapping of whole brain activity patterns associated with the intake of snack food in ad libitum fed rats.

    PubMed

    Hoch, Tobias; Kreitz, Silke; Gaffling, Simone; Pischetsrieder, Monika; Hess, Andreas

    2013-01-01

    Non-homeostatic hyperphagia, which is a major contributor to obesity-related hyperalimentation, is associated with the diet's molecular composition influencing, for example, the energy content. Thus, specific food items such as snack food may induce food intake independent from the state of satiety. To elucidate mechanisms how snack food may induce non-homeostatic food intake, it was tested if manganese-enhanced magnetic resonance imaging (MEMRI) was suitable for mapping the whole brain activity related to standard and snack food intake under normal behavioral situation. Application of the MnCl2 solution by osmotic pumps ensured that food intake was not significantly affected by the treatment. After z-score normalization and a non-affine three-dimensional registration to a rat brain atlas, significantly different grey values of 80 predefined brain structures were recorded in ad libitum fed rats after the intake of potato chips compared to standard chow at the group level. Ten of these areas had previously been connected to food intake, in particular to hyperphagia (e.g., dorsomedial hypothalamus or the anterior paraventricular thalamic nucleus) or to the satiety system (e.g., arcuate hypothalamic nucleus or solitary tract); 27 areas were related to reward/addiction including the core and shell of the nucleus accumbens, the ventral pallidum and the ventral striatum (caudate and putamen). Eleven areas associated to sleep displayed significantly reduced Mn2+ -accumulation and six areas related to locomotor activity showed significantly increased Mn2+ -accumulation after the intake of potato chips. The latter changes were associated with an observed significantly higher locomotor activity. Osmotic pump-assisted MEMRI proved to be a promising technique for functional mapping of whole brain activity patterns associated to nutritional intake under normal behavior. PMID:23408973

  1. Enhanced Z-LDA for Small Sample Size Training in Brain-Computer Interface Systems

    PubMed Central

    Gao, Dongrui; Zhang, Rui; Liu, Tiejun; Li, Fali; Ma, Teng; Lv, Xulin; Li, Peiyang; Yao, Dezhong; Xu, Peng

    2015-01-01

    Background. Usually the training set of online brain-computer interface (BCI) experiment is small. For the small training set, it lacks enough information to deeply train the classifier, resulting in the poor classification performance during online testing. Methods. In this paper, on the basis of Z-LDA, we further calculate the classification probability of Z-LDA and then use it to select the reliable samples from the testing set to enlarge the training set, aiming to mine the additional information from testing set to adjust the biased classification boundary obtained from the small training set. The proposed approach is an extension of previous Z-LDA and is named enhanced Z-LDA (EZ-LDA). Results. We evaluated the classification performance of LDA, Z-LDA, and EZ-LDA on simulation and real BCI datasets with different sizes of training samples, and classification results showed EZ-LDA achieved the best classification performance. Conclusions. EZ-LDA is promising to deal with the small sample size training problem usually existing in online BCI system. PMID:26550023

  2. Total and Regional Brain Volumes in a Population-Based Normative Sample from 4 to 18 Years: The NIH MRI Study of Normal Brain Development

    PubMed Central

    2012-01-01

    Using a population-based sampling strategy, the National Institutes of Health (NIH) Magnetic Resonance Imaging Study of Normal Brain Development compiled a longitudinal normative reference database of neuroimaging and correlated clinical/behavioral data from a demographically representative sample of healthy children and adolescents aged newborn through early adulthood. The present paper reports brain volume data for 325 children, ages 4.5–18 years, from the first cross-sectional time point. Measures included volumes of whole-brain gray matter (GM) and white matter (WM), left and right lateral ventricles, frontal, temporal, parietal and occipital lobe GM and WM, subcortical GM (thalamus, caudate, putamen, and globus pallidus), cerebellum, and brainstem. Associations with cross-sectional age, sex, family income, parental education, and body mass index (BMI) were evaluated. Key observations are: 1) age-related decreases in lobar GM most prominent in parietal and occipital cortex; 2) age-related increases in lobar WM, greatest in occipital, followed by the temporal lobe; 3) age-related trajectories predominantly curvilinear in females, but linear in males; and 4) small systematic associations of brain tissue volumes with BMI but not with IQ, family income, or parental education. These findings constitute a normative reference on regional brain volumes in children and adolescents. PMID:21613470

  3. Effects of formalin fixation on tissue optical properties of in-vitro brain samples

    NASA Astrophysics Data System (ADS)

    Anand, Suresh; Cicchi, Riccardo; Martelli, Fabrizio; Giordano, Flavio; Buccoliero, Anna Maria; Guerrini, Renzo; Pavone, Francesco S.

    2015-03-01

    Application of light spectroscopy based techniques for the detection of cancers have emerged as a promising approach for tumor diagnostics. In-vivo or freshly excised samples are normally used for point spectroscopic studies. However, ethical issues related to in-vivo studies, rapid decay of surgically excised tissues and sample availability puts a limitation on in-vivo and in-vitro studies. There has been a few studies reported on the application of formalin fixed samples with good discrimination capability. Usually formalin fixation is performed to prevent degradation of tissues after surgical resection. Fixing tissues in formalin prevents cell death by forming cross-linkages with proteins. Previous investigations have revealed that washing tissues fixed in formalin using phosphate buffered saline is known to reduce the effects of formalin during spectroscopic measurements. But this could not be the case with reflectance measurements. Hemoglobin is a principal absorbing medium in biological tissues in the visible range. Formalin fixation causes hemoglobin to seep out from red blood cells. Also, there could be alterations in the refractive index of tissues when fixed in formalin. In this study, we propose to investigate the changes in tissue optical properties between freshly excised and formalin fixed brain tissues. The results indicate a complete change in the spectral profile in the visible range where hemoglobin has its maximum absorption peaks. The characteristic bands of oxy-hemoglobin at 540, 580 nm and deoxy-hemoglobin at 555 nm disappear in the case of samples fixed in formalin. In addition, an increased spectral intensity was observed for the wavelengths greater than 650 nm where scattering phenomena are presumed to dominate.

  4. A novel papillomavirus in Adélie penguin (Pygoscelis adeliae) faeces sampled at the Cape Crozier colony, Antarctica.

    PubMed

    Varsani, Arvind; Kraberger, Simona; Jennings, Scott; Porzig, Elizabeth L; Julian, Laurel; Massaro, Melanie; Pollard, Annie; Ballard, Grant; Ainley, David G

    2014-06-01

    Papillomaviruses are epitheliotropic viruses that have circular dsDNA genomes encapsidated in non-enveloped virions. They have been found to infect a variety of mammals, reptiles and birds, but so far they have not been found in amphibians. Using a next-generation sequencing de novo assembly contig-informed recovery, we cloned and Sanger sequenced the complete genome of a novel papillomavirus from the faecal matter of Adélie penguins (Pygoscelis adeliae) nesting on Ross Island, Antarctica. The genome had all the usual features of a papillomavirus and an E9 ORF encoding a protein of unknown function that is found in all avian papillomaviruses to date. This novel papillomavirus genome shared ~60 % pairwise identity with the genomes of the other three known avian papillomaviruses: Fringilla coelebs papillomavirus 1 (FcPV1), Francolinus leucoscepus papillomavirus 1 (FlPV1) and Psittacus erithacus papillomavirus 1. Pairwise identity analysis and phylogenetic analysis of the major capsid protein gene clearly indicated that it represents a novel species, which we named Pygoscelis adeliae papillomavirus 1 (PaCV1). No evidence of recombination was detected in the genome of PaCV1, but we did detect a recombinant region (119 nt) in the E6 gene of FlPV1 with the recombinant region being derived from ancestral FcPV1-like sequences. Previously only paramyxoviruses, orthomyxoviruses and avian pox viruses have been genetically identified in penguins; however, the majority of penguin viral identifications have been based on serology or histology. This is the first report, to our knowledge, of a papillomavirus associated with a penguin species.

  5. A novel papillomavirus in Adélie penguin (Pygoscelis adeliae) faeces sampled at the Cape Crozier colony, Antarctica.

    PubMed

    Varsani, Arvind; Kraberger, Simona; Jennings, Scott; Porzig, Elizabeth L; Julian, Laurel; Massaro, Melanie; Pollard, Annie; Ballard, Grant; Ainley, David G

    2014-06-01

    Papillomaviruses are epitheliotropic viruses that have circular dsDNA genomes encapsidated in non-enveloped virions. They have been found to infect a variety of mammals, reptiles and birds, but so far they have not been found in amphibians. Using a next-generation sequencing de novo assembly contig-informed recovery, we cloned and Sanger sequenced the complete genome of a novel papillomavirus from the faecal matter of Adélie penguins (Pygoscelis adeliae) nesting on Ross Island, Antarctica. The genome had all the usual features of a papillomavirus and an E9 ORF encoding a protein of unknown function that is found in all avian papillomaviruses to date. This novel papillomavirus genome shared ~60 % pairwise identity with the genomes of the other three known avian papillomaviruses: Fringilla coelebs papillomavirus 1 (FcPV1), Francolinus leucoscepus papillomavirus 1 (FlPV1) and Psittacus erithacus papillomavirus 1. Pairwise identity analysis and phylogenetic analysis of the major capsid protein gene clearly indicated that it represents a novel species, which we named Pygoscelis adeliae papillomavirus 1 (PaCV1). No evidence of recombination was detected in the genome of PaCV1, but we did detect a recombinant region (119 nt) in the E6 gene of FlPV1 with the recombinant region being derived from ancestral FcPV1-like sequences. Previously only paramyxoviruses, orthomyxoviruses and avian pox viruses have been genetically identified in penguins; however, the majority of penguin viral identifications have been based on serology or histology. This is the first report, to our knowledge, of a papillomavirus associated with a penguin species. PMID:24686913

  6. Human Anti-Aβ IgGs Target Conformational Epitopes on Synthetic Dimer Assemblies and the AD Brain-Derived Peptide

    PubMed Central

    Welzel, Alfred T.; Williams, Angela D.; McWilliams-Koeppen, Helen P.; Acero, Luis; Weber, Alfred; Blinder, Veronika; Mably, Alex; Bunk, Sebastian; Hermann, Corinna; Farrell, Michael A.; Ehrlich, Hartmut J.; Schwarz, Hans P.; Walsh, Dominic M.; Solomon, Alan; O’Nuallain, Brian

    2012-01-01

    Soluble non-fibrillar assemblies of amyloid-beta (Aβ) and aggregated tau protein are the proximate synaptotoxic species associated with Alzheimer’s disease (AD). Anti-Aβ immunotherapy is a promising and advanced therapeutic strategy, but the precise Aβ species to target is not yet known. Previously, we and others have shown that natural human IgGs (NAbs) target diverse Aβ conformers and have therapeutic potential. We now demonstrate that these antibodies bound with nM avidity to conformational epitopes on plate-immobilized synthetic Aβ dimer assemblies, including synaptotoxic protofibrils, and targeted these conformers in solution. Importantly, NAbs also recognized Aβ extracted from the water-soluble phase of human AD brain, including species that migrated on denaturing PAGE as SDS-stable dimers. The critical reliance on Aβ’s conformational state for NAb binding, and not a linear sequence epitope, was confirmed by the antibody’s nM reactivity with plate-immobilized protofibrills, and weak uM binding to synthetic Aβ monomers and peptide fragments. The antibody’s lack of reactivity against a linear sequence epitope was confirmed by our ability to isolate anti-Aβ NAbs from intravenous immunoglobulin using affinity matrices, immunoglobulin light chain fibrils and Cibacron blue, which had no sequence similarity with the peptide. These findings suggest that further investigations on the molecular basis and the therapeutic/diagnostic potential of anti-Aβ NAbs are warranted. PMID:23209707

  7. Human anti-Aβ IgGs target conformational epitopes on synthetic dimer assemblies and the AD brain-derived peptide.

    PubMed

    Welzel, Alfred T; Williams, Angela D; McWilliams-Koeppen, Helen P; Acero, Luis; Weber, Alfred; Blinder, Veronika; Mably, Alex; Bunk, Sebastian; Hermann, Corinna; Farrell, Michael A; Ehrlich, Hartmut J; Schwarz, Hans P; Walsh, Dominic M; Solomon, Alan; O'Nuallain, Brian

    2012-01-01

    Soluble non-fibrillar assemblies of amyloid-beta (Aβ) and aggregated tau protein are the proximate synaptotoxic species associated with Alzheimer's disease (AD). Anti-Aβ immunotherapy is a promising and advanced therapeutic strategy, but the precise Aβ species to target is not yet known. Previously, we and others have shown that natural human IgGs (NAbs) target diverse Aβ conformers and have therapeutic potential. We now demonstrate that these antibodies bound with nM avidity to conformational epitopes on plate-immobilized synthetic Aβ dimer assemblies, including synaptotoxic protofibrils, and targeted these conformers in solution. Importantly, NAbs also recognized Aβ extracted from the water-soluble phase of human AD brain, including species that migrated on denaturing PAGE as SDS-stable dimers. The critical reliance on Aβ's conformational state for NAb binding, and not a linear sequence epitope, was confirmed by the antibody's nM reactivity with plate-immobilized protofibrills, and weak uM binding to synthetic Aβ monomers and peptide fragments. The antibody's lack of reactivity against a linear sequence epitope was confirmed by our ability to isolate anti-Aβ NAbs from intravenous immunoglobulin using affinity matrices, immunoglobulin light chain fibrils and Cibacron blue, which had no sequence similarity with the peptide. These findings suggest that further investigations on the molecular basis and the therapeutic/diagnostic potential of anti-Aβ NAbs are warranted.

  8. Detection of adulteration in honey samples added various sugar syrups with 13C/12C isotope ratio analysis method.

    PubMed

    Tosun, Murat

    2013-06-01

    Honey can be adulterated in various ways. One of the adulteration methods is the addition of different sugar syrups during or after honey production. Starch-based sugar syrups, high fructose corn syrup (HFCS), glucose syrup (GS) and saccharose syrups (SS), which are produced from beet or canes, can be used for adulterating honey. In this study, adulterated honey samples were prepared with the addition of HFCS, GS and SS (beet sugar) at a ratio of 0%, 10%, 20%, 40% and 50% by weight. (13)C/(12)C analysis was conducted on these adulterated honey samples using an isotope ratio mass spectrometer in combination with an elemental analyser (EA-IRMS). As a result, adulteration using C(4) sugar syrups (HFCS and GS) could be detected to a certain extent while adulteration of honey using C(3) sugar syrups (beet sugar) could not be detected. Adulteration by using SS (beet sugar) still has a serious detection problem, especially in countries in which beet is used in manufacturing sugar. For this reason, practice and analysis methods are needed to meet this deficit and to detect the adulterations precisely in the studies that will be conducted. PMID:23411291

  9. Human apolipoprotein E4 worsens acute axonal pathology but not amyloid-β immunoreactivity after traumatic brain injury in 3xTG-AD mice.

    PubMed

    Bennett, Rachel E; Esparza, Thomas J; Lewis, Hal A; Kim, Eddie; Mac Donald, Christine L; Sullivan, Patrick M; Brody, David L

    2013-05-01

    Apolipoprotein E4 (APOE4) genotype is a risk factor for poor outcome after traumatic brain injury (TBI), particularly in young patients, but the underlying mechanisms are not known. By analogy to effects of APOE4 on the risk of Alzheimer disease (AD), the APOE genotype may influence β-amyloid (Aβ) and tau deposition after TBI. To test this hypothesis, we crossed 3xTG-AD transgenic mice carrying 3 human familial AD mutations (PS1(M146V), tauP(301)L, and APP(SWE)) to human ApoE2-, ApoE3-, and ApoE4-targeted replacement mice. Six- to 8-month-old 3xTG-ApoE mice were assayed by quantitative immunohistochemistry for amyloid precursor protein (APP), Aβ(1-40) (Aβ40), Aβ(1-42) (Aβ42), total human tau, and phospho-serine 199 (pS199) tau at 24 hours after moderate controlled cortical impact. There were increased numbers of APP-immunoreactive axonal varicosities in 3xTG-ApoE4 mice versus the other genotypes. This finding was repeated in a separate cohort of ApoE4-targeted replacement mice without human transgenes compared with ApoE3 and ApoE2 mice. There were no differences between genotypes in the extent of intra-axonal Aβ40 and Aβ42; none of the mice had extracellular Aβ deposition. Regardless of injury status, 3xTG-ApoE4 mice had more total human tau accumulation in both somatodendritic and intra-axonal compartments than other genotypes. These results suggest that the APOE4 genotype may have a primary effect on the severity of axonal injury in acute TBI.

  10. Sample collection and amino acids analysis of extracellular fluid of mouse brain slices with low flow push-pull perfusion.

    PubMed

    Ojeda-Torres, G; Williams, L; Featherstone, D E; Shippy, S A

    2015-10-01

    Brain tissue slices are a common neuroscience model that allows relatively sophisticated analysis of neuronal networks in a simplified preparation. Most experimental methodology utilizes electrophysiological tools to probe these model systems. The work here demonstrates the adaptation of low-flow push-pull perfusion sampling (LFPS) to a brain slice system. LFPS is used to sample from the hippocampus of mouse brain slices. Perfusate amino acid levels are quantified following sampling with capillary electrophoresis. Glutamate was measured from the CA1 region of the hippocampus in slices taken from a cystine-glutamate transporter deletion mutant, xCT(-/-), and the background strain C57BL/6J. Sampling is performed over up to 6.5 h with standard tissue slice preparation and experimentation methods. Four amino acids were quantified to demonstrate the ability to perform LFPS and show good agreement with published literature. Perfusate glutamate levels are found to be significantly lower with xCT(-/-) slices (1.9(±0.5) μM) relative to controls (4.90(±1.1) μM). But, experiments with control slices show a significant decrease in glutamate over the 6 h sampling period that are not seen with xCT(-/-) slices. Increasing the LFPS sample collection rate during the first 90 min of sampling did not show a sampling artifact in perfusate glutamate content. Sampling immediately following slicing did not show an early increasing glutamate level that would be indicative of a significant contribution from blood or tissue damage. The data presented here show a complementarity to electrophysiological studies of tissue slices. The ability to characterize extracellular fluid chemical content with LFPS in these slices provides an alternative data stream for probing neurochemical signaling networks in brain tissue slices. PMID:26299259

  11. Evaluation of a Portable Microchip Electrophoresis Fluorescence Detection System for the Analysis of Amino Acid Neurotransmitters in Brain Dialysis Samples.

    PubMed

    Oborny, Nathan J; Costa, Elton E Melo; Suntornsuk, Leena; Abreu, Fabiane C; Lunte, Susan M

    2016-01-01

    A portable fluorescence detection system for use with microchip electrophoresis was developed and compared to a benchtop system. Using this system, six neuroactive amines commonly found in brain dialysate (arginine, citrulline, taurine, histamine, glutamate, and aspartate) were derivatized offline with naphthalene-2,3-dicarboxaldehyde/cyanide, separated electrophoretically, and detected by fluorescence. The limits of detection for the analytes of interest were 50 - 250 nM for the benchtop system and 250 nM - 1.3 μM for the portable system, both of which were adequate for most analyte detection in brain microdialysis samples. The portable system was then demonstrated for the detection of the same six amines in a rat brain microdialysis sample.

  12. Phocaeicola abscessus gen. nov., sp. nov., an anaerobic bacterium isolated from a human brain abscess sample.

    PubMed

    Al Masalma, Mouhamad; Raoult, Didier; Roux, Véronique

    2009-09-01

    A strictly anaerobic bacterial strain, 7401987T, was isolated from a human brain abscess sample. Cells were Gram-negative, non-spore-forming, coccoid to rod-shaped and motile by flagella in a lophotrichous arrangement. The isolate was asaccharolytic and the major cellular fatty acids were anteiso-C15:0 (28.2%), C16:0 (18.0%), iso-C15:0 (12.3%) and iso-C17:0 3-OH (11.7%). 16S rRNA gene sequence comparisons showed that the isolate was distantly related to members of the genera Bacteroides (<83.6% similarity), Parabacteroides (<79.9% similarity), Tannerella (<79.8% similarity), Dysgonomonas (<79.6% similarity), Porphyromonas (<79.3% similarity) and Prevotella (<78.9% similarity). The low 16S rRNA gene sequence similarity values and physiological and biochemical characteristics differentiated strain 7401987T from all known species and indicate that our isolate represents a novel species in a new genus within the phylum Bacteroidetes. The name Phocaeicola abscessus gen. nov., sp. nov. is proposed; the type strain of Phocaeicola abscessus is 7401987T (=CCUG 55929T=CSUR P22T=DSM 21584T). PMID:19620382

  13. Sources of Technical Variability in Quantitative LC-MS Proteomics: Human Brain Tissue Sample Analysis.

    SciTech Connect

    Piehowski, Paul D.; Petyuk, Vladislav A.; Orton, Daniel J.; Xie, Fang; Moore, Ronald J.; Ramirez Restrepo, Manuel; Engel, Anzhelika; Lieberman, Andrew P.; Albin, Roger L.; Camp, David G.; Smith, Richard D.; Myers, Amanda J.

    2013-05-03

    To design a robust quantitative proteomics study, an understanding of both the inherent heterogeneity of the biological samples being studied as well as the technical variability of the proteomics methods and platform is needed. Additionally, accurately identifying the technical steps associated with the largest variability would provide valuable information for the improvement and design of future processing pipelines. We present an experimental strategy that allows for a detailed examination of the variability of the quantitative LC-MS proteomics measurements. By replicating analyses at different stages of processing, various technical components can be estimated and their individual contribution to technical variability can be dissected. This design can be easily adapted to other quantitative proteomics pipelines. Herein, we applied this methodology to our label-free workflow for the processing of human brain tissue. For this application, the pipeline was divided into four critical components: Tissue dissection and homogenization (extraction), protein denaturation followed by trypsin digestion and SPE clean-up (digestion), short-term run-to-run instrumental response fluctuation (instrumental variance), and long-term drift of the quantitative response of the LC-MS/MS platform over the 2 week period of continuous analysis (instrumental stability). From this analysis, we found the following contributions to variability: extraction (72%) >> instrumental variance (16%) > instrumental stability (8.4%) > digestion (3.1%). Furthermore, the stability of the platform and its’ suitability for discovery proteomics studies is demonstrated.

  14. A stacking method to study the gamma-ray emission of source samples based on the co-adding of Fermi-LAT count maps

    NASA Astrophysics Data System (ADS)

    Huber, B.; Farnier, C.; Manalaysay, A.; Straumann, U.; Walter, R.

    2012-11-01

    Aims: We present a stacking method that makes use of co-added maps of gamma-ray counts produced from data taken with the Fermi Large Area Telescope. Sources with low integrated gamma-ray fluxes that are not detected individually may become detectable when their corresponding count maps are added. Methods: The combined data set is analyzed with a maximum likelihood method taking into account the contribution from point-like and diffuse background sources. For both simulated and real data, detection significance and integrated gamma-ray flux are investigated for different numbers of stacked sources using the public Fermi Science Tools for analysis and data preparation. Results: The co-adding is done such that potential source signals add constructively, in contrast to the signals from background sources, which allows the stacked data to be described with simply structured models. We show, for different scenarios, that the stacking method can be used to increase the cumulative significance of a sample of sources and to characterize the corresponding gamma-ray emission. The method can, for instance, help to search for gamma-ray emission from galaxy clusters.

  15. Functional brain networks formed using cross-sample entropy are scale free.

    PubMed

    Pritchard, Walter S; Laurienti, Paul J; Burdette, Jonathan H; Hayasaka, Satoru

    2014-08-01

    Over the previous decade, there has been an explosion of interest in network science, in general, and its application to the human brain, in particular. Most brain network investigations to date have used linear correlations (LinCorr) between brain areas to construct and then interpret brain networks. In this study, we applied an entropy-based method to establish functional connectivity between brain areas. This method is sensitive to both nonlinear and linear associations. The LinCorr-based and entropy-based techniques were applied to resting-state functional magnetic resonance imaging data from 10 subjects, and the resulting networks were compared. The networks derived from the entropy-based method exhibited power-law degree distributions. Moreover, the entropy-based networks had a higher clustering coefficient and a shorter path length compared with that of the LinCorr-based networks. While the LinCorr-based networks were assortative, with nodes with similar degrees preferentially connected, the entropy-based networks were disassortative, with high-degree hubs directly connected to low-degree nodes. It is likely that the differences in clustering and assortativity are due to "mega-hubs" in the entropy-based networks. These mega-hubs connect to a large majority of the nodes in the network. This is the first work clearly demonstrating differences between functional brain networks using linear and nonlinear techniques. The key finding is that the nonlinear technique produced networks with scale-free degree distributions. There remains debate among the neuroscience community as to whether human brains are scale free. These data support the argument that at least some aspects of the human brain are perhaps scale free.

  16. Functional Brain Networks Formed Using Cross-Sample Entropy Are Scale Free

    PubMed Central

    Pritchard, Walter S.; Burdette, Jonathan H.; Hayasaka, Satoru

    2014-01-01

    Abstract Over the previous decade, there has been an explosion of interest in network science, in general, and its application to the human brain, in particular. Most brain network investigations to date have used linear correlations (LinCorr) between brain areas to construct and then interpret brain networks. In this study, we applied an entropy-based method to establish functional connectivity between brain areas. This method is sensitive to both nonlinear and linear associations. The LinCorr-based and entropy-based techniques were applied to resting-state functional magnetic resonance imaging data from 10 subjects, and the resulting networks were compared. The networks derived from the entropy-based method exhibited power-law degree distributions. Moreover, the entropy-based networks had a higher clustering coefficient and a shorter path length compared with that of the LinCorr-based networks. While the LinCorr-based networks were assortative, with nodes with similar degrees preferentially connected, the entropy-based networks were disassortative, with high-degree hubs directly connected to low-degree nodes. It is likely that the differences in clustering and assortativity are due to “mega-hubs” in the entropy-based networks. These mega-hubs connect to a large majority of the nodes in the network. This is the first work clearly demonstrating differences between functional brain networks using linear and nonlinear techniques. The key finding is that the nonlinear technique produced networks with scale-free degree distributions. There remains debate among the neuroscience community as to whether human brains are scale free. These data support the argument that at least some aspects of the human brain are perhaps scale free. PMID:24946057

  17. Multimodal Raman-fluorescence spectroscopy of formalin fixed samples is able to discriminate brain tumors from dysplastic tissue

    NASA Astrophysics Data System (ADS)

    Anand, Suresh; Cicchi, Riccardo; Giordano, Flavio; Buccoliero, Anna Maria; Pavone, Francesco Saverio

    2014-05-01

    In the recent years, there has been a considerable surge in the application of spectroscopy for disease diagnosis. Raman and fluorescence spectra provide characteristic spectral profile related to biochemical and morphological changes when tissues progress from normal state towards malignancy. Spectroscopic techniques offer the advantage of being minimally invasive compared to traditional histopathology, real time and quantitative. In biomedical optical diagnostics, freshly excised specimens are preferred for making ex-vivo spectroscopic measurements. With regard to fresh tissues, if the lab is located far away from the clinic it could pose a problem as spectral measurements have to be performed immediately after dissection. Tissue samples are usually placed in a fixative agent such as 4% formaldehyde to preserve the samples before processing them for routine histopathological studies. Fixation prevents the tissues from decomposition by arresting autolysis. In the present study, we intend to investigate the possibility of using formalin fixed samples for discrimination of brain tumours from dysplastic tissue using Raman and fluorescence spectroscopy. Formalin fixed samples were washed with phosphate buffered saline for about 5 minutes in order to remove the effects of formalin during spectroscopic measurements. In case of fluorescence spectroscopy, changes in spectral profile have been observed in the region between 550-670 nm between dysplastic and tumor samples. For Raman measurements, we found significant differences in the spectral profiles between dysplasia and tumor. In conclusion, formalin fixed samples can be potentially used for the spectroscopic discrimination of tumor against dysplastic tissue in brain samples.

  18. Day of Injury CT and Late MRI Findings: Cognitive Outcome in a Pediatric Sample with Complicated Mild Traumatic Brain Injury

    PubMed Central

    Jantz, Paul B; Farrer, Thomas J.; Abildskov, Tracy J.; Dennis, Maureen; Gerhardt, Cynthia A.; Rubin, Kenneth H.; Stancin, Terry; Taylor, H. Gerry; Vannatta, Kathryn; Yeates, Keith Owen

    2016-01-01

    Objectives Complicated mild traumatic brain injury (mTBI) or cmTBI is based on the presence of visibly identifiable brain pathology on the day-of-injury computed tomography (CT) scan. In a pediatric sample the relation of DOI CT to late MRI findings and neuropsychological outcome was examined. Methods MRI (> 12 months) was obtained in pediatric cmTBI patients and a sample of orthopedically injured (OI) children. Those children with positive imaging findings (MRI+) were quantitatively compared to those without (MRI-) or with the OI sample. Groups were also compared in neurocognitive outcome from WASI subtests and the WISC-IV Processing Speed Index (PSI), along with the Test of Everyday Attention for Children (TEA-Ch) and a parent-rated behavioral functioning measure (ABAS-II). Results Despite the MRI+ group having significantly more DOI CT findings than the MRI-group, no quantitative differences were found. WASI Vocabulary and Matrix Reasoning scores were significantly lower, but not PSI, TEA-Ch or ABAS-II scores. MRI+ and MRI-groups did not differ on these measures. Conclusions Heterogeneity in the occurrence of MRI-identified focal pathology was not associated with uniform changes in quantitative analyses of brain structure in cmTBI. Increased number of DOI CT abnormalities was associated with lowered neuropsychological performance. PMID:26186038

  19. Characteristics of the Healthy Brain Project Sample: Representing Diversity among Study Participants

    ERIC Educational Resources Information Center

    Bryant, Lucinda L.; Laditka, James N.; Laditka, Sarah B.; Mathews, Anna E.

    2009-01-01

    Purpose: Description of study participants and documentation of the desired diversity in the Prevention Research Centers Healthy Aging Research Network's Workgroup on Promoting Cognitive Health large multisite study designed to examine attitudes about brain health, behaviors associated with its maintenance, and information-receiving preferences…

  20. Associations Between IQ, Total and Regional Brain Volumes and Demography in a Large Normative Sample of Healthy Children and Adolescents

    PubMed Central

    Lange, Nicholas; Froimowitz, Michael P.; Bigler, Erin D.; Lainhart, Janet E.

    2010-01-01

    In the course of efforts to establish quantitative MRI-based norms for healthy brain development (Brain Development Cooperative Group, 2006), previously unreported associations of parental education and temporal and frontal lobe volumes with full scale IQ and its verbal and performance subscales were discovered. Our findings were derived from the largest, most representative MRI sample to date of healthy children and adolescents, ages 4 years 10 months to 18 years 4 months. We first find that parental education has a strong association with IQ in children that is not mediated by total or regional brain volumes. Second, we find that our observed associations between temporal gray matter, temporal white matter and frontal white matter volumes with full scale IQ, between 0.14 to 0.27 in children and adolescents, are due in large part to their correlations with performance IQ and not verbal IQ. The volumes of other lobar gray and white matter, subcortical gray matter (thalamus, caudate nucleus, putamen and globus pallidus), cerebellum and brainstem do not contribute significantly to IQ variation. Third, we find that head circumference is an insufficient index of cerebral volume in typically developing older children and adolescents. The relations between total and regional brain volumes and IQ can best be discerned when additional variables known to be associated with IQ, especially parental education and other demographic measures, are considered concurrently. PMID:20446134

  1. Hairy AdS solitons

    NASA Astrophysics Data System (ADS)

    Anabalón, Andrés; Astefanesei, Dumitru; Choque, David

    2016-11-01

    We construct exact hairy AdS soliton solutions in Einstein-dilaton gravity theory. We examine their thermodynamic properties and discuss the role of these solutions for the existence of first order phase transitions for hairy black holes. The negative energy density associated to hairy AdS solitons can be interpreted as the Casimir energy that is generated in the dual filed theory when the fermions are antiperiodic on the compact coordinate.

  2. Application of time sampling in brain CT perfusion imaging for dose reduction

    NASA Astrophysics Data System (ADS)

    Lee, S. H.; Kim, J. H.; Kim, K. G.; Park, S. J.; Im, Jung Gi

    2007-03-01

    The purpose of this study is to determine a stable sampling rate not to be affected by sampling shift for reducing radiation exposure with time sampling and interpolation in cerebral perfusion CT examination. Original images were obtained every 1 second for 40 time series from 3 patients, respectively. Time sampling was performed with sampling intervals (SI) from 2 to 10 seconds. Sampling shift was applied from +1 to SI-1 for each sampling rate. For each patient, 30 tissue concentration time-course data were collected, and arterial input curves were fitted by gamma-variate function. The sinc function was introduced for interpolation. Deconvolution analysis based on SVD was performed for quantifying perfusion parameters. The perfusion values through time-varying sampling and interpolation were statistically compared with the original perfusion values. The mean CBF values with increase of sampling interval and shift magnitude from the collected data had a wider fluctuation pattern centering around the original mean CBF. The mean CBV values had a similar tendency to the mean CBF values, but a relatively narrower deviation. The mean MTT values were fluctuated reversely to the trend of the mean CBF values. The stable sampling interval for quantifying perfusion parameters with lower radiation exposure was statistically acceptable up to 4 seconds. These results indicate that sampling shift limits sampling rate for acquiring acceptable perfusion values. This study will help in selecting more reasonable sampling rate for low-radiation-dose CT examination.

  3. Functional System and Areal Organization of a Highly Sampled Individual Human Brain.

    PubMed

    Laumann, Timothy O; Gordon, Evan M; Adeyemo, Babatunde; Snyder, Abraham Z; Joo, Sung Jun; Chen, Mei-Yen; Gilmore, Adrian W; McDermott, Kathleen B; Nelson, Steven M; Dosenbach, Nico U F; Schlaggar, Bradley L; Mumford, Jeanette A; Poldrack, Russell A; Petersen, Steven E

    2015-08-01

    Resting state functional MRI (fMRI) has enabled description of group-level functional brain organization at multiple spatial scales. However, cross-subject averaging may obscure patterns of brain organization specific to each individual. Here, we characterized the brain organization of a single individual repeatedly measured over more than a year. We report a reproducible and internally valid subject-specific areal-level parcellation that corresponds with subject-specific task activations. Highly convergent correlation network estimates can be derived from this parcellation if sufficient data are collected-considerably more than typically acquired. Notably, within-subject correlation variability across sessions exhibited a heterogeneous distribution across the cortex concentrated in visual and somato-motor regions, distinct from the pattern of intersubject variability. Further, although the individual's systems-level organization is broadly similar to the group, it demonstrates distinct topological features. These results provide a foundation for studies of individual differences in cortical organization and function, especially for special or rare individuals. VIDEO ABSTRACT. PMID:26212711

  4. Detection of adulteration in mulberry pekmez samples added various sugar syrups with ¹³C/¹²C isotope ratio analysis method.

    PubMed

    Tosun, Murat

    2014-12-15

    Mulberry pekmez can be adulterated in different ways either during the production process or after production is completed. To identify these adulterations, stable carbon isotope ratio analysis (SCIRA) was performed on the model examples prepared by adding saccharose syrup (SS), glucose syrup (GS) and high fructose corn syrup (HFCS) into two different pure mulberry pekmez samples in the ratios of 0%, 10%, 30% and 50%. The δ(13)C ratio of the pure mulberry pekmez was determined as -26.60‰ on average, the saccharose syrup as -24.80‰, the glucose syrup as -11.20‰ and the high-fructose corn syrup as -11.40‰. In identifying the adulteration made to pekmez, especially with the high-fructose corn syrup, which is obtained from corn starch, and with the glucose syrup, the δ(13)C ratio comes into prominence. However it remains impossible identify the adulterations made with the saccharose, which is obtained from beet sugar, or invert sugar syrups. PMID:25038711

  5. Detection of adulteration in mulberry pekmez samples added various sugar syrups with ¹³C/¹²C isotope ratio analysis method.

    PubMed

    Tosun, Murat

    2014-12-15

    Mulberry pekmez can be adulterated in different ways either during the production process or after production is completed. To identify these adulterations, stable carbon isotope ratio analysis (SCIRA) was performed on the model examples prepared by adding saccharose syrup (SS), glucose syrup (GS) and high fructose corn syrup (HFCS) into two different pure mulberry pekmez samples in the ratios of 0%, 10%, 30% and 50%. The δ(13)C ratio of the pure mulberry pekmez was determined as -26.60‰ on average, the saccharose syrup as -24.80‰, the glucose syrup as -11.20‰ and the high-fructose corn syrup as -11.40‰. In identifying the adulteration made to pekmez, especially with the high-fructose corn syrup, which is obtained from corn starch, and with the glucose syrup, the δ(13)C ratio comes into prominence. However it remains impossible identify the adulterations made with the saccharose, which is obtained from beet sugar, or invert sugar syrups.

  6. Evaluation of elemental status of ancient human bone samples from Northeastern Hungary dated to the 10th century AD by XRF

    NASA Astrophysics Data System (ADS)

    János, I.; Szathmáry, L.; Nádas, E.; Béni, A.; Dinya, Z.; Máthé, E.

    2011-11-01

    The present study is a multielemental analysis of bone samples belonging to skeletal individuals originating from two contemporaneous (10th century AD) cemeteries (Tiszavasvári Nagy-Gyepáros and Nagycserkesz-Nádasibokor sites) in Northeastern Hungary, using the XRF analytical technique. Emitted X-rays were detected in order to determine the elemental composition of bones and to appreciate the possible influence of the burial environment on the elemental content of the human skeletal remains. Lumbar vertebral bodies were used for analysis. Applying the ED(P)XRF technique concentration of the following elements were determined: P, Ca, K, Na, Mg, Al, Cl, Mn, Fe, Zn, Br and Sr. The results indicated post mortem mineral exchange between the burial environment (soil) and bones (e.g. the enhanced levels of Fe and Mn) and referred to diagenetic alteration processes during burials. However, other elements such as Zn, Sr and Br seemed to be accumulated during the past life. On the basis of statistical analysis, clear separation could not be observed between the two excavation sites in their bone elemental concentrations which denoted similar diagenetic influences, environmental conditions. The enhanced levels of Sr might be connected with the past dietary habits, especially consumption of plant food.

  7. Frequency and impact of recurrent traumatic brain injury in a population-based sample.

    PubMed

    Theadom, Alice; Parmar, Priya; Jones, Kelly; Barker-Collo, Suzanne; Starkey, Nicola J; McPherson, Kathryn M; Ameratunga, Shanthi; Feigin, Valery L

    2015-05-15

    The aim of this study was to determine the frequency, mechanism(s), and impact of recurrent traumatic brain injury (TBI) over a 1-year period. Population-based TBI incidence and 1-year outcomes study with embedded case-control analysis. All participants (adults and children) who experienced a recurrent TBI (more than one) in the 12 months after an index injury and matched controls who sustained one TBI within the same period were enrolled in a population-based TBI incidence and outcomes study. Details of all recurrent TBIs sustained within 12 months of the initial index injury were recorded. Each recurrent TBI case was matched to a case sustaining one TBI based on age (±2 years), gender, and index TBI severity. Cognitive ability, disability, and postconcussion symptoms (PCS) were assessed 1 year after the index injury. Overall, 9.9% (n=72) of TBI cases experienced at least one recurrent TBI within the year after initial index injury. Males, people <35 years of age, and those who had experienced a TBI before their index injury were at highest risk of recurrent TBI. Recurrent TBI cases reported significantly increased PCS at 1 year, compared to the matched controls (n=72) sustaining one TBI. There was no difference in overall cognitive ability and disability between the two groups. People experiencing recurrent TBIs are more likely to experience increased frequency and severity of PCS. Greater public awareness of the potential effects of recurrent brain injury is needed. PMID:25334048

  8. Polyelectrolyte Microcapsules Dispersed in Silicone Rubber for in Vivo Sampling in Fish Brains.

    PubMed

    Xu, Jianqiao; Wu, Rongben; Huang, Shuyao; Yang, Muzi; Liu, Yan; Liu, Yuan; Jiang, Ruifen; Zhu, Fang; Ouyang, Gangfeng

    2015-10-20

    Direct detection of fluoxetine and its metabolite norfluoxetine in living fish brains was realized for the first time by using a novel solid-phase microextraction fiber, which was prepared by mixing the polyelectrolyte in the oligomer of silicone rubber and followed by in-mold heat-curing. The polyelectrolyte was finally encased in microcapsules dispersed in the cured silicone rubber. The fiber exhibited excellent interfiber reproducibility (5.4-7.1%, n = 6), intrafiber reproducibility (3.7-4.6%, n = 6), and matrix effect-resistant capacity. Due to the capacity of simultaneously extracting the neutral and the protonated species of the analytes at physiological pH, the fiber exhibited high extraction efficiencies to fluoxetine and norfluoxetine. Besides, the effect of the salinity on the extraction performance and the competitive sorption between the analytes were also evaluated. Based on the small-sized custom-made fiber, the concentrations of fluoxetine and norfluoxetine in the brains of living fish, which were exposed to waterborne fluoxetine at an environmentally relevant concentration, were determined and found 4.4 to 9.2 and 5.0 to 9.2 times those in the dorsal-epaxial muscle. The fiber can be used to detect various protonated bioactive compounds in living animal tissues. PMID:26403643

  9. Value Added?

    ERIC Educational Resources Information Center

    UCLA IDEA, 2012

    2012-01-01

    Value added measures (VAM) uses changes in student test scores to determine how much "value" an individual teacher has "added" to student growth during the school year. Some policymakers, school districts, and educational advocates have applauded VAM as a straightforward measure of teacher effectiveness: the better a teacher, the better students…

  10. STP Position Paper: Recommended Practices for Sampling and Processing the Nervous System (Brain, Spinal Cord, Nerve, and Eye) during Nonclinical General Toxicity Studies

    EPA Science Inventory

    The Society of Toxicologic Pathology charged a Nervous System Sampling Working Group with devising recommended practices to routinely screen the central and peripheral nervous systems in Good Laboratory Practice-type nonclinical general toxicity studies. Brains should be trimmed ...

  11. Brain lateralization and self-reported symptoms of ADHD in a population sample of adults: a dimensional approach

    PubMed Central

    Mohamed, Saleh M. H.; Börger, Norbert A.; Geuze, Reint H.; van der Meere, Jaap J.

    2015-01-01

    Many clinical studies reported a compromised brain lateralization in patients with Attention-Deficit/Hyperactivity Disorder (ADHD) without being conclusive about whether the deficit existed in the left or right hemisphere. It is well-recognized that studying ADHD dimensionally is more controlled for comorbid problems and medication effects, and provides more accurate assessment of the symptoms. Therefore, the present study applied the dimensional approach to test the relationship between brain lateralization and self-reported ADHD symptoms in a population sample. Eighty-five right-handed university students filled in the Conners’ Adult ADHD Rating Scales and performed a lateralization reaction time task. The task consists of two matching conditions: one condition requires nominal identification for letters tapping left hemisphere specialization (Letter Name-Identity condition) and the other one requires physical and visuospatial identification for shapes tapping right hemisphere specialization (Shape Physical-Identity condition). The letters or shapes to be matched are presented in left or right visual field of a fixation cross. For both task conditions, brain lateralization was indexed as the difference in mean reaction time between left and right visual field. Linear regression analyses, controlled for mood symptoms reported by a depression, anxiety, and stress scale, showed no relationship between the variables. These findings from a population sample of adults do not support the dimensionality of lateralized information processing deficit in ADHD symptomatology. However, group comparison analyses showed that subjects with high level of inattention symptoms close to or above the clinical cut-off had a reduced right hemisphere processing in the Shape Physical-Identity condition. PMID:26441789

  12. Neuropsychological Assessment Battery (NAB): Performance in a sample of patients with moderate-to-severe traumatic brain injury.

    PubMed

    Zgaljardic, Dennis J; Temple, Richard O

    2010-10-01

    The Neuropsychological Assessment Battery (NAB; Stern & White, 2003) is a comprehensive test battery that assesses five cognitive domains (Attention, Language, Memory, Spatial, and Executive Functions). The purpose of the current descriptive study was to present data on the index and primary test scores from the five main NAB cognitive modules in a sample of patients with moderate-to-severe traumatic brain injury (TBI) admitted to a residential postacute rehabilitation program. Twenty patients were administered all five main NAB modules upon recommendation from the NAB Screening module. The sample performed significantly worse than normal on tests that assess selective and divided attention, psychomotor speed, verbal memory, and cognitive flexibility. The largest proportion of patients performing below an established impairment cutoff (10th percentile) occurred on the Numbers and Letters, List Learning, Story Learning, Daily Living Memory, and Categories Tests. Significant performance decrements were not observed on any indices or tests from the Language or Spatial cognitive domain modules. The pattern of performance on the NAB demonstrated by the current sample is consistent with the neuropsychological profile observed in postacute patients with moderate-to-severe TBI without focal deficits (e.g., aphasia), demonstrating its relative sensitivity in this patient population. A comparison between the current study sample and a related clinical sample from the NAB standardization data is discussed.

  13. On the Importance of Accounting for Competing Risks in Pediatric Brain Cancer: II. Regression Modeling and Sample Size

    SciTech Connect

    Tai, Bee-Choo; Grundy, Richard; Machin, David

    2011-03-15

    Purpose: To accurately model the cumulative need for radiotherapy in trials designed to delay or avoid irradiation among children with malignant brain tumor, it is crucial to account for competing events and evaluate how each contributes to the timing of irradiation. An appropriate choice of statistical model is also important for adequate determination of sample size. Methods and Materials: We describe the statistical modeling of competing events (A, radiotherapy after progression; B, no radiotherapy after progression; and C, elective radiotherapy) using proportional cause-specific and subdistribution hazard functions. The procedures of sample size estimation based on each method are outlined. These are illustrated by use of data comparing children with ependymoma and other malignant brain tumors. The results from these two approaches are compared. Results: The cause-specific hazard analysis showed a reduction in hazards among infants with ependymoma for all event types, including Event A (adjusted cause-specific hazard ratio, 0.76; 95% confidence interval, 0.45-1.28). Conversely, the subdistribution hazard analysis suggested an increase in hazard for Event A (adjusted subdistribution hazard ratio, 1.35; 95% confidence interval, 0.80-2.30), but the reduction in hazards for Events B and C remained. Analysis based on subdistribution hazard requires a larger sample size than the cause-specific hazard approach. Conclusions: Notable differences in effect estimates and anticipated sample size were observed between methods when the main event showed a beneficial effect whereas the competing events showed an adverse effect on the cumulative incidence. The subdistribution hazard is the most appropriate for modeling treatment when its effects on both the main and competing events are of interest.

  14. Preprocessing and Quality Control Strategies for Illumina DASL Assay-Based Brain Gene Expression Studies with Semi-Degraded Samples.

    PubMed

    Chow, Maggie L; Winn, Mary E; Li, Hai-Ri; April, Craig; Wynshaw-Boris, Anthony; Fan, Jian-Bing; Fu, Xiang-Dong; Courchesne, Eric; Schork, Nicholas J

    2012-01-01

    Available statistical preprocessing or quality control analysis tools for gene expression microarray datasets are known to greatly affect downstream data analysis, especially when degraded samples, unique tissue samples, or novel expression assays are used. It is therefore important to assess the validity and impact of the assumptions built in to preprocessing schemes for a dataset. We developed and assessed a data preprocessing strategy for use with the Illumina DASL-based gene expression assay with partially degraded postmortem prefrontal cortex samples. The samples were obtained from individuals with autism as part of an investigation of the pathogenic factors contributing to autism. Using statistical analysis methods and metrics such as those associated with multivariate distance matrix regression and mean inter-array correlation, we developed a DASL-based assay gene expression preprocessing pipeline to accommodate and detect problems with microarray-based gene expression values obtained with degraded brain samples. Key steps in the pipeline included outlier exclusion, data transformation and normalization, and batch effect and covariate corrections. Our goal was to produce a clean dataset for subsequent downstream differential expression analysis. We ultimately settled on available transformation and normalization algorithms in the R/Bioconductor package lumi based on an assessment of their use in various combinations. A log2-transformed, quantile-normalized, and batch and seizure-corrected procedure was likely the most appropriate for our data. We empirically tested different components of our proposed preprocessing strategy and believe that our results suggest that a preprocessing strategy that effectively identifies outliers, normalizes the data, and corrects for batch effects can be applied to all studies, even those pursued with degraded samples.

  15. Cytoskeletal Pathologies of Age-Related Diseases between Elderly Sri Lankan (Colombo) and Indian (Bangalore) Brain Samples.

    PubMed

    Wijesinghe, Printha; Shankar, S K; Chickabasaviah, Yasha T; Gorrie, Catherine; Amaratunga, Dhammika; Hulathduwa, Sanjayah; Kumara, K Sunil; Samarasinghe, Kamani; Suh, Yoo Hun; Steinbusch, H W; De Silva, K Ranil D

    2016-01-01

    Within South Asia, Sri Lanka represents fastest aging with 13% of the population was aged over 60's in 2011, whereas in India it was 8%. Majority of the Sri Lankan population based genetic studies have confirmed their origin on Indian mainland. As there were inadequate data on aging cytoskeletal pathologies of these two nations with their close genetic affiliations, we performed a comparison on their elderly. Autopsy brain samples of 50 individuals from Colombo, Sri Lanka (mean age 72.1 yrs ± 7.8, mean ± S.D.) and 42 individuals from Bangalore, India (mean age 65.9 yrs ± 9.3) were screened for neurodegenerative pathologies using immunohistochemical techniques. A total of 79 cases with incomplete clinical history (Colombo- 47 and Bangalore- 32) were subjected to statistical analysis and 13 cases, clinically diagnosed with dementia and/or Parkinsonism disorders were excluded. As per National Institute on Aging- Alzheimer's Association guidelines, between Colombo and Bangalore samples, Alzheimer's disease neuropathologic change for intermediate/ high level was 4.25% vs. 3.12% and low level was 19.15% vs. 15.62% respectively. Pathologies associated with Parkinsonism including brainstem predominant Lewy bodies- 6.4% and probable progressive supra nuclear palsy- 2.13% were found solely in Colombo samples. Alzheimer related pathologies were not different among elders, however, in Colombo males, neurofibrillary tangle grade was significantly higher in the region of hippocampus (odds ratio = 1.46, 95% confidence interval = 0.07-0.7) and at risk in midbrain substantia nigra (p = 0.075). Other age-related pathologies including spongiform changes (p < 0.05) and hippocampus cell loss in dentate gyrus region (p < 0.05) were also identified prominently in Colombo samples. Taken together, aging cytoskeletal pathologies are comparatively higher in elderly Sri Lankans and this might be due to their genetic, dietary and/ or environmental variations.

  16. Cytoskeletal Pathologies of Age-Related Diseases between Elderly Sri Lankan (Colombo) and Indian (Bangalore) Brain Samples.

    PubMed

    Wijesinghe, Printha; Shankar, S K; Chickabasaviah, Yasha T; Gorrie, Catherine; Amaratunga, Dhammika; Hulathduwa, Sanjayah; Kumara, K Sunil; Samarasinghe, Kamani; Suh, Yoo Hun; Steinbusch, H W; De Silva, K Ranil D

    2016-01-01

    Within South Asia, Sri Lanka represents fastest aging with 13% of the population was aged over 60's in 2011, whereas in India it was 8%. Majority of the Sri Lankan population based genetic studies have confirmed their origin on Indian mainland. As there were inadequate data on aging cytoskeletal pathologies of these two nations with their close genetic affiliations, we performed a comparison on their elderly. Autopsy brain samples of 50 individuals from Colombo, Sri Lanka (mean age 72.1 yrs ± 7.8, mean ± S.D.) and 42 individuals from Bangalore, India (mean age 65.9 yrs ± 9.3) were screened for neurodegenerative pathologies using immunohistochemical techniques. A total of 79 cases with incomplete clinical history (Colombo- 47 and Bangalore- 32) were subjected to statistical analysis and 13 cases, clinically diagnosed with dementia and/or Parkinsonism disorders were excluded. As per National Institute on Aging- Alzheimer's Association guidelines, between Colombo and Bangalore samples, Alzheimer's disease neuropathologic change for intermediate/ high level was 4.25% vs. 3.12% and low level was 19.15% vs. 15.62% respectively. Pathologies associated with Parkinsonism including brainstem predominant Lewy bodies- 6.4% and probable progressive supra nuclear palsy- 2.13% were found solely in Colombo samples. Alzheimer related pathologies were not different among elders, however, in Colombo males, neurofibrillary tangle grade was significantly higher in the region of hippocampus (odds ratio = 1.46, 95% confidence interval = 0.07-0.7) and at risk in midbrain substantia nigra (p = 0.075). Other age-related pathologies including spongiform changes (p < 0.05) and hippocampus cell loss in dentate gyrus region (p < 0.05) were also identified prominently in Colombo samples. Taken together, aging cytoskeletal pathologies are comparatively higher in elderly Sri Lankans and this might be due to their genetic, dietary and/ or environmental variations. PMID:26906356

  17. Cluster subtypes on the California Verbal Learning Test-Second Edition (CVLT-II) in a traumatic brain injury sample.

    PubMed

    DeJong, Joy; Donders, Jacobus

    2010-11-01

    Subtypes of learning and memory on the California Verbal Learning Test-Second Edition (CVLT-II; Delis, Kramer, Kaplan, & Ober, 2000) were examined in a clinical sample of 223 persons with traumatic brain injury (TBI), screened to remove individuals with complicating premorbid (e.g., psychiatric) or comorbid (e.g., financial compensation-seeking) histories. The z scores from 4 key CVLT-II variables were entered into a two-stage cluster analysis. These variables were selected to represent 4 latent constructs, identified in a recent confirmatory factor analysis: List A1 (Attention Span), List A5 (Learning Efficiency), Long Delay Free Recall (Delayed Memory), and False Positives (Inaccurate Memory). Six reliable subtypes were found (similar to those in the standardization sample) that were differentiated by both level and pattern of performance, with differences in level of performance meaningfully related to length of coma. In conclusion, the impact of TBI on CVLT-II performance can be manifested in various patterns that are not specifically unique, but are affected by injury severity. PMID:20408004

  18. Analysis of oxysterols and vitamin D metabolites in mouse brain and cell line samples by ultra-high-performance liquid chromatography-atmospheric pressure photoionization-mass spectrometry.

    PubMed

    Ahonen, Linda; Maire, Florian B R; Savolainen, Mari; Kopra, Jaakko; Vreeken, Rob J; Hankemeier, Thomas; Myöhänen, Timo; Kylli, Petri; Kostiainen, Risto

    2014-10-17

    We have developed an ultra-high-performance liquid chromatography-atmospheric pressure photoionization-tandem mass spectrometric (UHPLC-APPI-MS/MS) method for the simultaneous quantitative analyses of several oxysterols and vitamin D metabolites in mouse brain and cell line samples. An UHPLC-APPI-high resolution mass spectrometric (UHPLC-APPI-HRMS) method that uses a quadrupole-time of flight mass spectrometer was also developed for confirmatory analysis and for the identification of non-targeted oxysterols. Both methods showed good quantitative performance. Furthermore, APPI provides high ionization efficiency for determining oxysterols and vitamin D related compounds without the time consuming derivatization step needed in the conventionally used electrospray ionization method to achieve acceptable sensitivity. Several oxysterols were quantified in mouse brain and cell line samples. Additionally, 25-hydroxyvitamin D3 was detected in mouse brain samples for the first time.

  19. The NADPH oxidase NOX2 as a novel biomarker for suicidality: evidence from human post mortem brain samples

    PubMed Central

    Schiavone, S; Neri, M; Mhillaj, E; Morgese, M G; Cantatore, S; Bove, M; Riezzo, I; Tucci, P; Pomara, C; Turillazzi, E; Cuomo, V; Trabace, L

    2016-01-01

    Recent evidence points towards a role of oxidative stress in suicidality. However, few studies were carried out on the sources of reactive oxygen species (ROS) in subjects with suicidal behaviour. We have previously demonstrated that the NADPH oxidase NOX2-derived oxidative stress has a major role in the development of neuropathological alterations observed in an animal model of psychosis. Here, we investigated the possible increase in NOX2 in post mortem brain samples of subjects who died by asphyctic suicide (AS) compared with controls (CTRL) and subjects who died by non-suicidal asphyxia (NSA). We found that NOX2 expression was significantly higher in the cortex of AS subjects than in the other two experimental groups. NOX2 immunostaining was mainly detected in GABAergic neurons, with a minor presence of NOX2-positive-stained cells in glutamatergic and dopaminergic neurons, as well as astrocytes and microglia. A sustained increase in the expression of 8-hydroxy-2'-deoxyguanosine, an indirect marker of oxidative stress, was also detected in the cortex of AS subjects, compared with CTRL and NSA subjects. A significant elevation in cortical interleukin-6 immunoreactivity in AS subjects suggested an involvement of cytokine-associated molecular pathways in NOX2 elevations. Our results suggest that the increase in NOX2-derived oxidative stress in the brain might be involved in the neuropathological pathways leading to suicidal behaviour. These results may open innovative insights in the identification of new pathogenetic and necroscopic biomarkers, predictive for suicidality and potentially useful for suicide prevention. PMID:27187235

  20. Estimation of the unbound brain concentration of P-glycoprotein substrates or nonsubstrates by a serial cerebrospinal fluid sampling technique in rats.

    PubMed

    Mariappan, T Thanga; Kurawattimath, Vishwanath; Gautam, Shashyendra Singh; Kulkarni, Chetan P; Kallem, Rajareddy; Taskar, Kunal S; Marathe, Punit H; Mandlekar, Sandhya

    2014-02-01

    The unbound concentration in plasma drives the transport of the drug into the brain, and the unbound drug concentration in the central nervous system (CNS) drives the interaction with the target eliciting the pharmacological effect. Delivery of the drug to the CNS is a challenge because of the unique neurovascular unit, which restricts the passage of drugs into the brain. The efflux transporters [especially P-glycoprotein (P-gp)] present at the blood-brain barrier (BBB) act as one of the major detractors for keeping drugs outside the CNS. The cerebrospinal fluid (CSF) drug concentration has been used as a surrogate for unbound brain concentrations and has proven to be a good indicator to relate to CNS activity. Herein, we have established a serial CSF sampling technique in rats, which allowed CSF sampling from a single animal and reduced the number of animals required, as well as the interanimal variance associated with a composite/terminal study design. Concentrations in the CSF sampled from the cisterna magna serially from the same rat were compared with the concentrations obtained from discrete CSF sampling and with brain concentrations. The serial CSF sampling technique was also authenticated by ensuring no change in the barrier without any indication of damage caused by the repeated puncture of cisterna magna. This technique was corroborated using three passively permeable compounds (carbamazepine, theophylline, and propranolol), three P-gp substrates (quinidine, verapamil, and digoxin), and one l-amino acid uptake transporter substrate (gabapentin). The P-gp substrates were also used in separate studies with the P-gp inhibitor elacridar to assess the effect on CSF concentration versus brain concentration on P-gp inhibition. The CSF concentration and unbound brain concentration were comparable (within 3-fold) for all compounds, including P-gp substrates even in the presence of elacridar. Therefore, this technique can prove to be beneficial for predicting the

  1. Mitochondrial DNA Rearrangement Spectrum in Brain Tissue of Alzheimer’s Disease: Analysis of 13 Cases

    PubMed Central

    Chen, Yucai; Liu, Changsheng; Parker, William Davis; Chen, Hongyi; Beach, Thomas G.; Liu, Xinhua; Serrano, Geidy E.; Lu, Yanfen; Huang, Jianjun; Yang, Kunfang; Wang, Chunmei

    2016-01-01

    Background Mitochondrial dysfunction may play a central role in the pathologic process of Alzheimer’s disease (AD), but there is still a scarcity of data that directly links the pathology of AD with the alteration of mitochondrial DNA. This study aimed to provide a comprehensive assessment of mtDNA rearrangement events in AD brain tissue. Patients and Methods Postmortem frozen human brain cerebral cortex samples were obtained from the Banner Sun Health Research Institute Brain and Body Donation Program, Sun City, AZ. Mitochondria were isolated and direct sequence by using MiSeq®, and analyzed by relative software. Results Three types of mitochondrial DNA (mtDNA) rearrangements have been seen in post mortem human brain tissue from patients with AD and age matched control. These observed rearrangements include a deletion, F-type rearrangement, and R-type rearrangement. We detected a high level of mtDNA rearrangement in brain tissue from cognitively normal subjects, as well as the patients with Alzheimer's disease (AD). The rate of rearrangements was calculated by dividing the number of positive rearrangements by the coverage depth. The rearrangement rate was significantly higher in AD brain tissue than in control brain tissue (17.9%versus 6.7%; p = 0.0052). Of specific types of rearrangement, deletions were markedly increased in AD (9.2% versus 2.3%; p = 0.0005). Conclusions Our data showed that failure of mitochondrial DNA in AD brain might be important etiology of AD pathology. PMID:27299301

  2. DIS in AdS

    SciTech Connect

    Albacete, Javier L.; Kovchegov, Yuri V.; Taliotis, Anastasios

    2009-03-23

    We calculate the total cross section for the scattering of a quark-anti-quark dipole on a large nucleus at high energy for a strongly coupled N = 4 super Yang-Mills theory using AdS/CFT correspondence. We model the nucleus by a metric of a shock wave in AdS{sub 5}. We then calculate the expectation value of the Wilson loop (the dipole) by finding the extrema of the Nambu-Goto action for an open string attached to the quark and antiquark lines of the loop in the background of an AdS{sub 5} shock wave. We find two physically meaningful extremal string configurations. For both solutions we obtain the forward scattering amplitude N for the quark dipole-nucleus scattering. We study the onset of unitarity with increasing center-of-mass energy and transverse size of the dipole: we observe that for both solutions the saturation scale Q{sub s} is independent of energy/Bjorken-x and depends on the atomic number of the nucleus as Q{sub s}{approx}A{sup 1/3}. Finally we observe that while one of the solutions we found corresponds to the pomeron intercept of {alpha}{sub P} = 2 found earlier in the literature, when extended to higher energy or larger dipole sizes it violates the black disk limit. The other solution we found respects the black disk limit and yields the pomeron intercept of {alpha}{sub P} = 1.5. We thus conjecture that the right pomeron intercept in gauge theories at strong coupling may be {alpha}{sub P} = 1.5.

  3. Factor Structure of the Brief Multidimensional Measure of Religiousness/Spirituality in US and Indian Samples with Traumatic Brain Injury.

    PubMed

    Johnstone, Brick; Bhushan, Braj; Hanks, Robin; Yoon, Dong Pil; Cohen, Daniel

    2016-04-01

    The aim of this paper was to determine the factor structure of the Brief Multidimensional Measure of Religiousness/Spirituality (BMMRS) based on a sample of individuals from diverse cultures (i.e., USA, India), ethnicities (i.e., Caucasian, African-American, South Asian), and religions (i.e., Christian, Muslim, Hindu). A total of 109 individuals with traumatic brain injury (TBI) were included. Participants completed the BMMRS as part of a broader study on spirituality, religion, prosocial behaviors, and neuropsychological function. A principal components factor analysis with varimax rotation and Kaiser normalization identified a six-factor solution accounting for 72% of the variance in scores. Five of the factors were deemed to be interpretable and were labeled based on face validity as: (1) Positive Spirituality/Religious Practices; (2) Positive Congregational Support; (3) Negative Spirituality/Negative Congregational Support; (4) Organizational Religion; and (5) Forgiveness. The results were generally consistent with previous studies, suggesting the existence of universal religious, spiritual, and congregational support factors across different cultures and faith traditions. For health outcomes research, it is suggested that the BMMRS factors may be best conceptualized as measuring the following general domains: (a) emotional connectedness with a higher power (i.e., spirituality, positive/negative); (b) culturally based behavioral practices (i.e., religion); and (c) social support (i.e., positive/negative). The results indicate that factor relationships may differ among spiritual, religious, and congregational support variables according to culture and/or religious tradition. PMID:26708139

  4. A Confirmatory Factor Analysis of the California Verbal Learning Test-Second Edition (CVLT-II) in a Traumatic Brain Injury Sample

    ERIC Educational Resources Information Center

    DeJong, Joy; Donders, Jacobus

    2009-01-01

    The latent structure of the California Verbal Learning Test-Second Edition (CVLT-II) was examined in a clinical sample of 223 persons with traumatic brain injury that had been screened to remove individuals with complicating premorbid (e.g., psychiatric) or comorbid (e.g., financial compensation seeking) histories. Analyses incorporated the "z"…

  5. Improving the Sensitivity of the Xpert MTB/RIF Assay on Sputum Pellets by Decreasing the Amount of Added Sample Reagent: a Laboratory and Clinical Evaluation

    PubMed Central

    Amisano, Danielle; Mboowa, Gerald; Ssengooba, Willy; Blakemore, Robert; Kubiak, Rachel W.; Armstrong, Derek T.; Jones, Martin; Manabe, Yukari C.; Joloba, Moses L.; Ellner, Jerrold J.; Dorman, Susan E.; Alland, David

    2015-01-01

    The Xpert MTB/RIF (Xpert) assay permits rapid near-patient detection of Mycobacterium tuberculosis in sputum; however, the test sensitivity remains suboptimal in paucibacillary specimens that are negative for acid-fast bacilli using smear microscopy. Xpert testing includes dilution with sample reagent, and when processed sputum pellets are tested, the recommended sample reagent/pellet ratio is 3:1. We evaluated whether a decreased sample reagent/pellet ratio of 2:1 increased Xpert sensitivity compared to the recommended 3:1. The limit of detection was determined by inoculating serial dilutions of M. tuberculosis into sputum samples, preparing sputum pellets, and testing each pellet by Xpert at both sample reagent ratios. Processed sputum pellets obtained from M. tuberculosis culture-positive clinical specimens were also tested by Xpert at both ratios. Among spiked sputum pellets, the limit of detection was 1,478 CFU/ml (95% confidence interval [CI], 1,211 to 1,943) at a 3:1 ratio and decreased to 832 CFU/ml (95% CI, 671 to 1,134) at 2:1. The proportion of specimens in which M. tuberculosis was detected was greater at 2:1 than at 3:1 for almost all numbers of CFU/ml; this difference was most prominent at lower numbers of CFU/ml. Among 134 concentrated sputum pellets from the clinical study, the sensitivity of Xpert at 2:1 was greater than at 3:1 overall (80% versus 72%; P = 0.03) and for smear-negative specimens (67% versus 58%; P = 0.12). For Xpert testing of sputum pellets, using a lower sample reagent/pellet ratio increased M. tuberculosis detection, especially for paucibacillary specimens. Our study supports use of a 2:1 sample reagent/pellet dilution for Xpert testing of sputum pellets. PMID:25653410

  6. Brain investigation and brain conceptualization

    PubMed Central

    Redolfi, Alberto; Bosco, Paolo; Manset, David; Frisoni, Giovanni B.

    Summary The brain of a patient with Alzheimer’s disease (AD) undergoes changes starting many years before the development of the first clinical symptoms. The recent availability of large prospective datasets makes it possible to create sophisticated brain models of healthy subjects and patients with AD, showing pathophysiological changes occurring over time. However, these models are still inadequate; representations are mainly single-scale and they do not account for the complexity and interdependence of brain changes. Brain changes in AD patients occur at different levels and for different reasons: at the molecular level, changes are due to amyloid deposition; at cellular level, to loss of neuron synapses, and at tissue level, to connectivity disruption. All cause extensive atrophy of the whole brain organ. Initiatives aiming to model the whole human brain have been launched in Europe and the US with the goal of reducing the burden of brain diseases. In this work, we describe a new approach to earlier diagnosis based on a multimodal and multiscale brain concept, built upon existing and well-characterized single modalities. PMID:24139654

  7. EXTENSION OF THE INVERSE ADDING-DOUBLING METHOD TO THE MEASUREMENT OF WAVELENGTH-DEPENDENT ABSORPTION AND SCATTERING COEFFICIENTS OF BIOLOGICAL SAMPLES

    SciTech Connect

    Allegood, M.S.; Baba, J.S.

    2008-01-01

    Light interaction with biological tissue can be described using three parameters: the scattering and absorption coeffi cients (μs and μa), as well as the anisotropy (g) which describes the directional dependence of the scattered photons. Accurately determining these optical properties for different tissue types at specifi c wavelengths simultaneously would be benefi cial for a variety of different biomedical applications. The goal of this project was to take a user defi ned g-value and determine the remaining two parameters for a specifi ed wavelength range. A fully automated computer program and process was developed to collect data for all wavelengths in a timely and accurate manner. LabVIEW® was used to write programs to automate raw intensity data collection from a spectrometer equipped integrating sphere, conversion of the data into a format for analysis via Scott Prahl’s Inverse Adding-Doubling (IAD) C code execution, and fi nally computation of the optical properties based on the output from the IAD code. To allow data to be passed effi ciently between LabVIEW® and C code program modules, the two were combined into a single program (OPT 3.1). OPT 3.1 was tested using tissue mimicking phantoms. Determination of the absorption and scattering coeffi cients showed excellent agreement with theory for wavelengths where the user inputted single g-value was suffi ciently precise. Future improvements entail providing for multi-wavelength g-value entry to extend the accuracy of results to encompass the complete multispectral range. Ultimately, the data collection process and algorithms developed through this effort will be used to examine actual biological tissues for the purpose of building and refi ning models for light-tissue interactions.

  8. Gibbs distribution for statistical analysis of graphical data with a sample application to fcMRI brain images.

    PubMed

    La Rosa, Patricio S; Brooks, Terrence L; Deych, Elena; Shands, Berkley; Prior, Fred; Larson-Prior, Linda J; Shannon, William D

    2016-02-20

    This paper develops object-oriented data analysis (OODA) statistical methods that are novel and complementary to existing methods of analysis of human brain scan connectomes, defined as graphs representing brain anatomical or functional connectivity. OODA is an emerging field where classical statistical approaches (e.g., hypothesis testing, regression, estimation, and confidence intervals) are applied to data objects such as graphs or functions. By analyzing data objects directly we avoid loss of information that occurs when data objects are transformed into numerical summary statistics. By providing statistical tools that analyze sets of connectomes without loss of information, new insights into neurology and medicine may be achieved. In this paper we derive the formula for statistical model fitting, regression, and mixture models; test their performance in simulation experiments; and apply them to connectomes from fMRI brain scans collected during a serial reaction time task study. Software for fitting graphical object-oriented data analysis is provided. PMID:26608238

  9. Gibbs distribution for statistical analysis of graphical data with a sample application to fcMRI brain images.

    PubMed

    La Rosa, Patricio S; Brooks, Terrence L; Deych, Elena; Shands, Berkley; Prior, Fred; Larson-Prior, Linda J; Shannon, William D

    2016-02-20

    This paper develops object-oriented data analysis (OODA) statistical methods that are novel and complementary to existing methods of analysis of human brain scan connectomes, defined as graphs representing brain anatomical or functional connectivity. OODA is an emerging field where classical statistical approaches (e.g., hypothesis testing, regression, estimation, and confidence intervals) are applied to data objects such as graphs or functions. By analyzing data objects directly we avoid loss of information that occurs when data objects are transformed into numerical summary statistics. By providing statistical tools that analyze sets of connectomes without loss of information, new insights into neurology and medicine may be achieved. In this paper we derive the formula for statistical model fitting, regression, and mixture models; test their performance in simulation experiments; and apply them to connectomes from fMRI brain scans collected during a serial reaction time task study. Software for fitting graphical object-oriented data analysis is provided.

  10. Sensitive method for determination of picogram amounts of epinephrine and other catecholamines in microdissected samples of rat brain using liquid chromatography with electrochemical detection.

    PubMed

    Opacka-Juffry, J; Tacconelli, F; Coen, C W

    1988-12-01

    Liquid chromatography with high-sensitivity electrochemical detection has been employed to measure picogram amounts of epinephrine and other catecholamines in microdissected samples of the rat hypothalamus. Tissue catecholamines are purified by solvent extraction; this provides better selectivity and recovery than methods involving alumina. The solvent extraction technique has been modified in order to eliminate its major disadvantage, the presence of electroactive substances separating with catecholamines. Detection limits of below 1 pg allow for analysis of catecholamines including epinephrine in very small brain samples such as micropunches.

  11. Three-dimensional printed sample load/inject valves enabling online monitoring of extracellular calcium and zinc ions in living rat brains.

    PubMed

    Su, Cheng-Kuan; Hsia, Sheng-Chieh; Sun, Yuh-Chang

    2014-08-01

    We have developed a simple and low-cost flow injection system coupled to a quadruple ICP-MS for the direct and continuous determination of multi-element in microdialysates. To interface microdialysis sampling to an inductively coupled plasma mass spectrometer (ICP-MS), we employed 3D printing to manufacture an as-designed sample load/inject valve featuring an in-valve sample loop for precise handling of microliter samples with a dissolved solids content of 0.9% NaCl (w/v). To demonstrate the practicality of our developed on-line system, we applied the 3D printed valve equipped a 5-μL sample loop to minimize the occurrence of salt matrix effects and facilitate an online dynamic monitoring of extracellular calcium and zinc ions in living rat brains. Under the practical condition (temporal resolution: 10h(-1)), dynamic profiling of these two metal ions in living rat brain extracellular fluid after probe implantation (the basal values for Ca and Zn were 12.11±0.10mg L(-1) and 1.87±0.05μg L(-1), respectively) and real-time monitoring of the physiological response to excitotoxic stress elicited upon perfusing a solution of 2.5mM N-methyl-d-aspartate were performed. PMID:25064244

  12. Microbiota-Gut-Brain Axis: Yeast Species Isolated from Stool Samples of Children with Suspected or Diagnosed Autism Spectrum Disorders and In Vitro Susceptibility Against Nystatin and Fluconazole.

    PubMed

    Kantarcioglu, A Serda; Kiraz, Nuri; Aydin, Ahmet

    2016-02-01

    Autism spectrum disorder (ASD) is a general term for a group of complex neurodevelopmental disorders of brain development that limits a person's ability to function normally. Etiology has not been clearly defined up to date. However, gut microbiota and the bidirectional communication between the gastrointestinal tract and brain, the so-called microbiota-gut-brain axis, are hypothesized, which may be involved in the etiology of several mental disorders. Recent reports suggest that Candida, particularly Candida albicans, growth in intestines may cause lower absorption of carbohydrates and minerals and higher toxin levels which are thought to contribute autistic behaviors. The aim of this study was to identify the 3-year deposited yeasts isolated from stool samples of children with diagnosed or suspected ASD and to determine in vitro activity of nystatin and fluconazole against these isolates using Clinical Laboratory Standards Institute M27-A3 guidelines. A 17-year retrospective assessment was also done using our laboratory records. Among the species identified, intrinsically fluconazole-resistant Candida krusei (19.8 %) and Candida glabrata (14.8 %) with elevated MICs were remarkable. Overall, C. albicans (57.4 %) was the most commonly isolated species in 17 years. The species identification and/or antifungal susceptibility tests have to be performed using the strain isolated from stool sample, to select the appropriate antifungal agent, if antimycotic therapy is needed.

  13. Changes in brain volume and cognition in a randomized trial of exercise and social interaction in a community-based sample of non-demented Chinese elders.

    PubMed

    Mortimer, James A; Ding, Ding; Borenstein, Amy R; DeCarli, Charles; Guo, Qihao; Wu, Yougui; Zhao, Qianhua; Chu, Shugang

    2012-01-01

    Physical exercise has been shown to increase brain volume and improve cognition in randomized trials of non-demented elderly. Although greater social engagement was found to reduce dementia risk in observational studies, randomized trials of social interventions have not been reported. A representative sample of 120 elderly from Shanghai, China was randomized to four groups (Tai Chi, Walking, Social Interaction, No Intervention) for 40 weeks. Two MRIs were obtained, one before the intervention period, the other after. A neuropsychological battery was administered at baseline, 20 weeks, and 40 weeks. Comparison of changes in brain volumes in intervention groups with the No Intervention group were assessed by t-tests. Time-intervention group interactions for neuropsychological measures were evaluated with repeated-measures mixed models. Compared to the No Intervention group, significant increases in brain volume were seen in the Tai Chi and Social Intervention groups (p < 0.05). Improvements also were observed in several neuropsychological measures in the Tai Chi group, including the Mattis Dementia Rating Scale score (p = 0.004), the Trailmaking Test A (p = 0.002) and B (p = 0.0002), the Auditory Verbal Learning Test (p = 0.009), and verbal fluency for animals (p = 0.01). The Social Interaction group showed improvement on some, but fewer neuropsychological indices. No differences were observed between the Walking and No Intervention groups. The findings differ from previous clinical trials in showing increases in brain volume and improvements in cognition with a largely non-aerobic exercise (Tai Chi). In addition, intellectual stimulation through social interaction was associated with increases in brain volume as well as with some cognitive improvements.

  14. Intact lipid imaging of mouse brain samples: MALDI, nanoparticle-laser desorption ionization, and 40 keV argon cluster secondary ion mass spectrometry.

    PubMed

    Mohammadi, Amir Saeid; Phan, Nhu T N; Fletcher, John S; Ewing, Andrew G

    2016-09-01

    We have investigated the capability of nanoparticle-assisted laser desorption ionization mass spectrometry (NP-LDI MS), matrix-assisted laser desorption ionization (MALDI) MS, and gas cluster ion beam secondary ion mass spectrometry (GCIB SIMS) to provide maximum information available in lipid analysis and imaging of mouse brain tissue. The use of Au nanoparticles deposited as a matrix for NP-LDI MS is compared to MALDI and SIMS analysis of mouse brain tissue and allows selective detection and imaging of groups of lipid molecular ion species localizing in the white matter differently from those observed using conventional MALDI with improved imaging potential. We demonstrate that high-energy (40 keV) GCIB SIMS can act as a semi-soft ionization method to extend the useful mass range of SIMS imaging to analyze and image intact lipids in biological samples, closing the gap between conventional SIMS and MALDI techniques. The GCIB SIMS allowed the detection of more intact lipid compounds in the mouse brain compared to MALDI with regular organic matrices. The 40 keV GCIB SIMS also produced peaks observed in the NP-LDI analysis, and these peaks were strongly enhanced in intensity by exposure of the sample to trifluororacetic acid (TFA) vapor prior to analysis. These MS techniques for imaging of different types of lipids create a potential overlap and cross point that can enhance the information for imaging lipids in biological tissue sections. Graphical abstract Schematic of mass spectral imaging of a mouse brain tissue using GCIB-SIMS and MALDI techniques. PMID:27549796

  15. Intact lipid imaging of mouse brain samples: MALDI, nanoparticle-laser desorption ionization, and 40 keV argon cluster secondary ion mass spectrometry.

    PubMed

    Mohammadi, Amir Saeid; Phan, Nhu T N; Fletcher, John S; Ewing, Andrew G

    2016-09-01

    We have investigated the capability of nanoparticle-assisted laser desorption ionization mass spectrometry (NP-LDI MS), matrix-assisted laser desorption ionization (MALDI) MS, and gas cluster ion beam secondary ion mass spectrometry (GCIB SIMS) to provide maximum information available in lipid analysis and imaging of mouse brain tissue. The use of Au nanoparticles deposited as a matrix for NP-LDI MS is compared to MALDI and SIMS analysis of mouse brain tissue and allows selective detection and imaging of groups of lipid molecular ion species localizing in the white matter differently from those observed using conventional MALDI with improved imaging potential. We demonstrate that high-energy (40 keV) GCIB SIMS can act as a semi-soft ionization method to extend the useful mass range of SIMS imaging to analyze and image intact lipids in biological samples, closing the gap between conventional SIMS and MALDI techniques. The GCIB SIMS allowed the detection of more intact lipid compounds in the mouse brain compared to MALDI with regular organic matrices. The 40 keV GCIB SIMS also produced peaks observed in the NP-LDI analysis, and these peaks were strongly enhanced in intensity by exposure of the sample to trifluororacetic acid (TFA) vapor prior to analysis. These MS techniques for imaging of different types of lipids create a potential overlap and cross point that can enhance the information for imaging lipids in biological tissue sections. Graphical abstract Schematic of mass spectral imaging of a mouse brain tissue using GCIB-SIMS and MALDI techniques.

  16. Segmented strings in AdS 3

    NASA Astrophysics Data System (ADS)

    Callebaut, Nele; Gubser, Steven S.; Samberg, Andreas; Toldo, Chiara

    2015-11-01

    We study segmented strings in flat space and in AdS 3. In flat space, these well known classical motions describe strings which at any instant of time are piecewise linear. In AdS 3, the worldsheet is composed of faces each of which is a region bounded by null geodesics in an AdS 2 subspace of AdS 3. The time evolution can be described by specifying the null geodesic motion of kinks in the string at which two segments are joined. The outcome of collisions of kinks on the worldsheet can be worked out essentially using considerations of causality. We study several examples of closed segmented strings in AdS 3 and find an unexpected quasi-periodic behavior. We also work out a WKB analysis of quantum states of yo-yo strings in AdS 5 and find a logarithmic term reminiscent of the logarithmic twist of string states on the leading Regge trajectory.

  17. Polarised black holes in AdS

    NASA Astrophysics Data System (ADS)

    Costa, Miguel S.; Greenspan, Lauren; Oliveira, Miguel; Penedones, João; Santos, Jorge E.

    2016-06-01

    We consider solutions in Einstein-Maxwell theory with a negative cosmological constant that asymptote to global AdS 4 with conformal boundary {S}2× {{{R}}}t. At the sphere at infinity we turn on a space-dependent electrostatic potential, which does not destroy the asymptotic AdS behaviour. For simplicity we focus on the case of a dipolar electrostatic potential. We find two new geometries: (i) an AdS soliton that includes the full backreaction of the electric field on the AdS geometry; (ii) a polarised neutral black hole that is deformed by the electric field, accumulating opposite charges in each hemisphere. For both geometries we study boundary data such as the charge density and the stress tensor. For the black hole we also study the horizon charge density and area, and further verify a Smarr formula. Then we consider this system at finite temperature and compute the Gibbs free energy for both AdS soliton and black hole phases. The corresponding phase diagram generalizes the Hawking-Page phase transition. The AdS soliton dominates the low temperature phase and the black hole the high temperature phase, with a critical temperature that decreases as the external electric field increases. Finally, we consider the simple case of a free charged scalar field on {S}2× {{{R}}}t with conformal coupling. For a field in the SU(N ) adjoint representation we compare the phase diagram with the above gravitational system.

  18. Altered Expression Patterns of Inflammation-Associated and Trophic Molecules in Substantia Nigra and Striatum Brain Samples from Parkinson's Disease, Incidental Lewy Body Disease and Normal Control Cases

    PubMed Central

    Walker, Douglas G.; Lue, Lih-Fen; Serrano, Geidy; Adler, Charles H.; Caviness, John N.; Sue, Lucia I.; Beach, Thomas G.

    2016-01-01

    Evidence of inflammation has been consistently associated with pathology in Parkinson's disease (PD)-affected brains, and has been suggested as a causative factor. Dopaminergic neurons in the substantia nigra (SN) pars compacta, whose loss results in the clinical symptoms associated with PD, are particularly susceptible to inflammatory damage and oxidative stress. Inflammation in the striatum, where SN dopaminergic neurons project, is also a feature of PD brains. It is not known whether inflammatory changes occur first in striatum or SN. Many animal models of PD have implicated certain inflammatory molecules with dopaminergic cell neuronal loss; however, there have been few studies to validate these findings by measuring the levels of these and other inflammatory factors in human PD brain samples. This study also included samples from incidental Lewy body disease (ILBD) cases, since ILBD is considered a non-symptomatic precursor to PD, with subjects having significant loss of tyrosine hydroxylase-producing neurons. We hypothesized that there may be a progressive change in key inflammatory factors in ILBD samples intermediate between neurologically normal and PD. To address this, we used a quantitative antibody-array platform (Raybiotech-Quantibody arrays) to measure the levels of 160 different inflammation-associated cytokines, chemokines, growth factors, and related molecules in extracts of SN and striatum from clinically and neuropathologically characterized PD, ILBD, and normal control cases. Patterns of changes in inflammation and related molecules were distinctly different between SN and striatum. Our results showed significantly different levels of interleukin (IL)-5, IL-15, monokine induced by gamma interferon, and IL-6 soluble receptor in SN between disease groups. A different panel of 13 proteins with significant changes in striatum, with IL-15 as the common feature, was identified. Although the ability to detect some proteins was limited by sensitivity

  19. Hg sup 2+ induces GTP-tubulin interactions in rat brain similar to those observed in Alzheimer's disease

    SciTech Connect

    Duhr, E.; Pendergrass, C.; Kasarskis, E.; Slevin, J.; Haley, B. )

    1991-03-11

    The pathogenesis of Alzheimer's Disease (AD) is unknown. Using SDS-PAGE and autoradiography the authors' laboratory has shown: (1) that the tubulin in AD brain is less photolabeled by ({sup 32}P)8N{sub 3}GTP than is tubulin from control brain and (2) that low {mu}M levels of preformed Hg{sup 2+}EDTA specifically blocked interactions of tubulin-({sup 32}P)8N{sub 3}GTP in control human brain homogenates giving a photolabeling profile identical to AD brain. Elevated levels of Hg{sup 2+} have been reported in AD brain by others. Earlier work using ({sup 32}P)8N{sub 3}GTP with Al{sup 3+} treated rat and rabbit brain showed no differences from control with regards to tubulin photolabeling. However, our latest data show that brain samples from Hg{sup 2+} fed rats display an abolished GTP-tubulin interaction similar to AD brain samples as determined by ({sup 32}P)8N{sub 3}GTP photolabeling profiles. Removal of Hg{sup 2+} from treated rats did not reverse the effect. These results suggest that certain complexed forms of Hg{sup 2+} must be considered as a potential source for the etiology of AD.

  20. Brain aging, Alzheimer's disease, and mitochondria

    PubMed Central

    Swerdlow, Russell H.

    2011-01-01

    The relationship between brain aging and Alzheimer’s disease (AD) is contentious. One view holds AD results when brain aging surpasses a threshold. The other view postulates AD is not a consequence of brain aging. This review discusses this conundrum from the perspective of different investigative lines that have tried to address it, as well as from the perspective of the mitochondrion, an organelle that appears to play a role in both AD and brain aging. Specific issues addressed include the question of whether AD and brain aging should be conceptually lumped or split, the extent to which AD and brain aging potentially share common molecular mechanisms, whether beta amyloid should be primarily considered a marker of AD or simply brain aging, and the definition of AD itself. PMID:21920438

  1. AdS duals of matrix strings

    NASA Astrophysics Data System (ADS)

    Morales, Jose F.; Samtleben, Henning

    2003-06-01

    We review recent work on the holographic duals of type II and heterotic matrix string theories described by warped AdS3 supergravities. In particular, we compute the spectra of Kaluza-Klein primaries for type I, II supergravities on warped AdS3 × S7 and match them with the primary operators in the dual two-dimensional gauge theories. The presence of non-trivial warp factors and dilaton profiles requires a modification of the familiar dictionary between masses and 'scaling' dimensions of fields and operators. We present these modifications for the general case of domain wall/QFT correspondences between supergravities on warped AdSd+1 × Sq geometries and super Yang-Mills theories with 16 supercharges.

  2. Different Brain Regions are Infected with Fungi in Alzheimer’s Disease

    PubMed Central

    Pisa, Diana; Alonso, Ruth; Rábano, Alberto; Rodal, Izaskun; Carrasco, Luis

    2015-01-01

    The possibility that Alzheimer’s disease (AD) has a microbial aetiology has been proposed by several researchers. Here, we provide evidence that tissue from the central nervous system (CNS) of AD patients contain fungal cells and hyphae. Fungal material can be detected both intra- and extracellularly using specific antibodies against several fungi. Different brain regions including external frontal cortex, cerebellar hemisphere, entorhinal cortex/hippocampus and choroid plexus contain fungal material, which is absent in brain tissue from control individuals. Analysis of brain sections from ten additional AD patients reveals that all are infected with fungi. Fungal infection is also observed in blood vessels, which may explain the vascular pathology frequently detected in AD patients. Sequencing of fungal DNA extracted from frozen CNS samples identifies several fungal species. Collectively, our findings provide compelling evidence for the existence of fungal infection in the CNS from AD patients, but not in control individuals. PMID:26468932

  3. Pathological changes in Alzheimer"s brain evaluated with fluorescence emission analysis (FEA)

    NASA Astrophysics Data System (ADS)

    Christov, Alexander; Ottman, Todd; Grammas, Paula

    2004-07-01

    Development of AD is associated with cerebrovascular deposition of amyloid beta (Aβ) as well as a progressive increase in vasular collagen content. Both AΒ and collagen are naturally fluorescent compounds when exposed to UV light. We analyzed autofluorescence emitted from brain tissue samples and isolated brain resistance vessels harvested postmortem from patients with Alzheimer's disease (AD) and age-matched controls. Fluorescence emission, excited at 355 nm with an Nd:YAG laser, was measured using a fiber-optic based fluorescence spectroscopic system for tissue analysis. Significantly higher values of fluorescence emission intensity (P<0.001) in the spectral region from 465 to 490 nm were detected in brain resistance vessel samples from AD patients compared to the normal individuals. Results from western blot analysis showed elevated levels of type I and type III collagen, and reduced levels of type IV collagen in resistance vessels from AD patients, compared to control samples. In addition, using direct scanning of the cortical suface for fluoresxcence emission by the laser-induced fluorescence spectroscopy system we detected a significantly (P<0.05) higher level of apoptosis in AD brain tissue compared to age-matched controls. Fluorescence emission analysis (FEA) appears to be a sensitive technique for detecting structural changes in AD brain tissue.

  4. Volume shrinkage of bone, brain and muscle tissue in sample preparation for micro-CT and light sheet fluorescence microscopy (LSFM).

    PubMed

    Buytaert, Jan; Goyens, Jana; De Greef, Daniel; Aerts, Peter; Dirckx, Joris

    2014-08-01

    Two methods are especially suited for tomographic imaging with histological detail of macroscopic samples that consist of multiple tissue types (bone, muscle, nerve or fat): Light sheet (based) fluorescence microscopy (LSFM) and micro-computed tomography (micro-CT). Micro-CT requires staining with heavy chemical elements (and thus fixation and sometimes dehydration) in order to make soft tissue imageable when measured alongside denser structures. LSMF requires fixation, decalcification, dehydration, clearing and staining with a fluorescent dye. The specimen preparation of both imaging methods is prone to shrinkage, which is often not mentioned, let alone quantified. In this paper the presence and degree of shrinkage are quantitatively identified for the selected preparation methods/stains. LSFM delivers a volume shrinkage of 17% for bone, 56% for muscle and 62% for brain tissue. The three most popular micro-CT stains (phosphotungstic acid, iodine with potassium iodide, and iodine in absolute ethanol) deliver a volume shrinkage ranging from 10 to 56% for muscle and 27-66% for brain, while bone does not shrink in micro-CT preparation. PMID:24963987

  5. The Impact of Docosahexaenoic Acid on Alzheimer's Disease: Is There a Role of the Blood-Brain Barrier?

    PubMed

    Pan, Yijun; Khalil, Hanan; Nicolazzo, Joseph A

    2015-01-01

    There currently is no cure or established preventative treatment for Alzheimer's disease (AD). Considering the increasing aging population and the subsequent high prevalence of AD worldwide, identifying a cost-effective way to prevent AD is an essential unmet medical need. Relative to healthy human brain samples, postmortem AD brain samples have been shown to exhibit lower docosahexaenoic acid (DHA) levels, an essential polyunsaturated fatty acid required for normal neuronal function. However, findings from different studies are controversial and it is not clear whether this alteration in DHA brain levels is a cause or consequence of AD. Animal studies have also demonstrated that administration of DHA can alleviate the underlying pathophysiology of AD, including but not limited to amyloid pathology, tau pathology, and neuroinflammation. Moreover, DHA has been suggested to exert cognitive-enhancing effects and epidemiological studies have suggested that regular consumption of fish or omega-3 fatty acid enriched diets can attenuate the cognitive decline in AD and/or lower the risk of developing AD. However, the beneficial effects of DHA in AD have not been clearly demonstrated by current human randomised-control trials. In addition, the underlying reasons for the lower brain levels of DHA in AD remain to be fully characterised. However, given that the brain has limited capacity to produce DHA de novo and obtains DHA from the plasma, one plausible explanation for the lower brain levels of DHA in AD is reduced bloodbrain barrier (BBB) transport of this fatty acid in AD, as has been reported in one mouse model of AD. Unfortunately, the actual mechanisms governing the BBB transport of DHA in healthy conditions are not clearly understood, complicating the relationship between reduced BBB transport of DHA, attenuated DHA brain levels and AD pathology. The purpose of this review, therefore, is to summarise the findings of the biochemical, functional and epidemiological

  6. Preparation of highly stable fullerene C60 decorated graphene oxide nanocomposite and its sensitive electrochemical detection of dopamine in rat brain and pharmaceutical samples.

    PubMed

    Thirumalraj, Balamurugan; Palanisamy, Selvakumar; Chen, Shen-Ming; Lou, Bih-Show

    2016-01-15

    The research community has continuously paid much attention on the preparation of hybrid of carbon nanomaterials owing to combine their unique properties. Herein, we report the preparation of highly stable fullerene C60 (C60) wrapped graphene oxide (GO) nanocomposite by using a simple sonication method. The fabricated GO-C60 nanocomposite modified glassy carbon electrode shows a good sensitivity and lower oxidation overpotential towards dopamine (DA) than that of pristine GO and C60. The fabricated sensor detects the DA in the linear response range of 0.02-73.5μM. The limit of detection is estimated to be 0.008μM based on 3σ with a sensitivity of 4.23μAμM(-1)cm(-2). The fabricated sensor also exhibits other features such as good selectivity, stability, reproducibility and repeatability. The proposed sensor exhibits good practicality towards the detection of DA in rat brain and commercial DA injection samples.

  7. Agricultural Education: Value Adding.

    ERIC Educational Resources Information Center

    Riesenberg, Lou E.; And Others

    1989-01-01

    This issue develops the theme of "Agricultural Education--Value Adding." The concept value adding has been a staple in the world of agricultural business for describing adding value to a commodity that would profit the producer and the local community. Agricultural education should add value to individuals and society to justify agricultural…

  8. Plasma and brain fatty acid profiles in mild cognitive impairment and Alzheimer's disease.

    PubMed

    Cunnane, Stephen C; Schneider, Julie A; Tangney, Christine; Tremblay-Mercier, Jennifer; Fortier, Mélanie; Bennett, David A; Morris, Martha Clare

    2012-01-01

    Alzheimer's disease (AD) is generally associated with lower omega-3 fatty acid intake from fish but despite numerous studies, it is still unclear whether there are differences in omega-3 fatty acids in plasma or brain. In matched plasma and brain samples provided by the Memory and Aging Project, fatty acid profiles were quantified in several plasma lipid classes and in three brain cortical regions. Fatty acid data were expressed as % composition and as concentrations (mg/dL for plasma or mg/g for brain). Differences in plasma fatty acid profiles between AD, mild cognitive impairment (MCI), and those with no cognitive impairment (NCI) were most apparent in the plasma free fatty acids (lower oleic acid isomers and omega-6 fatty acids in AD) and phospholipids (lower omega-3 fatty acids in AD). In brain, % DHA was lower only in phosphatidylserine of mid-frontal cortex and superior temporal cortex in AD compared to NCI (-14% and -12%, respectively; both p < 0.05). The only significant correlation between plasma and brain fatty acids was between % DHA in plasma total lipids and % DHA in phosphatidylethanolamine of the angular gyrus, but only in the NCI group (+0.77, p < 0.05). We conclude that AD is associated with altered plasma status of both DHA and other fatty acids unrelated to DHA, and that the lipid class-dependent nature of these differences reflects a combination of differences in intake and metabolism. PMID:22466064

  9. Associations between a History of Traumatic Brain Injuries and Current Cigarette Smoking, Substance Use, and Elevated Psychological Distress in a Population Sample of Canadian Adults.

    PubMed

    Ilie, Gabriela; Adlaf, Edward M; Mann, Robert E; Ialomiteanu, Anca; Hamilton, Hayley; Rehm, Jürgen; Asbridge, Mark; Cusimano, Michael D

    2015-07-15

    This study describes the prevalence of reported history of traumatic brain injury (TBI) and its association with reports of current substance use, cigarette smoking, and psychological distress among Canadian adults in a population sample. A cross-sectional sample of 1999 Ontario adults 18-93 years of age were surveyed by telephone in 2011 as part of the Center for Addiction and Mental Health's ongoing representative survey of adult mental health and substance use in Ontario, Canada. Loss of consciousness for at least 5 min or at least one overnight hospitalization resulting from symptoms associated with the TBI injury represented minimum criteria for TBI. An estimated 16.8% (95% confidence interval, 14.8, 19.0) of adults reported a TBI in their lifetime. Men had higher prevalence of TBI than women. Adults who reported a history of TBI had higher odds of reported past-year daily smoking (adjusted odds ratio [AOR] = 2.15), using cannabis (AOR = 2.80) and nonmedical opioids (AOR = 2.90), as well as screened significantly for recent elevated psychological distress (AOR = 1.97) in the past few weeks, compared to adults without a history of TBI. Co-occurrence of a history of TBI with current elevated psychological distress and substance use warrants vigilance among medical practitioners to assess the possibility of a history of TBI during reviews of the history leading to the occurrence of these conditions. PMID:25496189

  10. Associations between a History of Traumatic Brain Injuries and Current Cigarette Smoking, Substance Use, and Elevated Psychological Distress in a Population Sample of Canadian Adults

    PubMed Central

    Adlaf, Edward M.; Mann, Robert E.; Ialomiteanu, Anca; Hamilton, Hayley; Rehm, Jürgen; Asbridge, Mark; Cusimano, Michael D.

    2015-01-01

    Abstract This study describes the prevalence of reported history of traumatic brain injury (TBI) and its association with reports of current substance use, cigarette smoking, and psychological distress among Canadian adults in a population sample. A cross-sectional sample of 1999 Ontario adults 18–93 years of age were surveyed by telephone in 2011 as part of the Center for Addiction and Mental Health's ongoing representative survey of adult mental health and substance use in Ontario, Canada. Loss of consciousness for at least 5 min or at least one overnight hospitalization resulting from symptoms associated with the TBI injury represented minimum criteria for TBI. An estimated 16.8% (95% confidence interval, 14.8, 19.0) of adults reported a TBI in their lifetime. Men had higher prevalence of TBI than women. Adults who reported a history of TBI had higher odds of reported past-year daily smoking (adjusted odds ratio [AOR]=2.15), using cannabis (AOR=2.80) and nonmedical opioids (AOR=2.90), as well as screened significantly for recent elevated psychological distress (AOR=1.97) in the past few weeks, compared to adults without a history of TBI. Co-occurrence of a history of TBI with current elevated psychological distress and substance use warrants vigilance among medical practitioners to assess the possibility of a history of TBI during reviews of the history leading to the occurrence of these conditions. PMID:25496189

  11. Associations between a History of Traumatic Brain Injuries and Current Cigarette Smoking, Substance Use, and Elevated Psychological Distress in a Population Sample of Canadian Adults.

    PubMed

    Ilie, Gabriela; Adlaf, Edward M; Mann, Robert E; Ialomiteanu, Anca; Hamilton, Hayley; Rehm, Jürgen; Asbridge, Mark; Cusimano, Michael D

    2015-07-15

    This study describes the prevalence of reported history of traumatic brain injury (TBI) and its association with reports of current substance use, cigarette smoking, and psychological distress among Canadian adults in a population sample. A cross-sectional sample of 1999 Ontario adults 18-93 years of age were surveyed by telephone in 2011 as part of the Center for Addiction and Mental Health's ongoing representative survey of adult mental health and substance use in Ontario, Canada. Loss of consciousness for at least 5 min or at least one overnight hospitalization resulting from symptoms associated with the TBI injury represented minimum criteria for TBI. An estimated 16.8% (95% confidence interval, 14.8, 19.0) of adults reported a TBI in their lifetime. Men had higher prevalence of TBI than women. Adults who reported a history of TBI had higher odds of reported past-year daily smoking (adjusted odds ratio [AOR] = 2.15), using cannabis (AOR = 2.80) and nonmedical opioids (AOR = 2.90), as well as screened significantly for recent elevated psychological distress (AOR = 1.97) in the past few weeks, compared to adults without a history of TBI. Co-occurrence of a history of TBI with current elevated psychological distress and substance use warrants vigilance among medical practitioners to assess the possibility of a history of TBI during reviews of the history leading to the occurrence of these conditions.

  12. Topographic regulation of kinase activity in Alzheimer's disease brains.

    PubMed

    Grant, Philip; Pant, Harish C

    2002-08-01

    phosphorylation in control white extracts, the kinase activities of P13(suc1)-derived multimeric complexes from gray and white matter were also similar in control and AD brains. Here, too, variances between control and AD distributions were significantly different (p < 0.001-0.02) suggesting that the P13 complexes were different. We also found differences in the Western blot profiles of P13suc1-associated kinases and cytoskeletal proteins; higher expression of phosphorylated NF-H and PHF-tau in gray matter of AD brains was detected. We believe that such differences in P13 complexes from human control and AD brain samples displaying extensive heterogeneity in age, post mortem time and clinical history, may be important.

  13. Sex steroid levels and AD-like pathology in 3xTgAD mice.

    PubMed

    Overk, C R; Perez, S E; Ma, C; Taves, M D; Soma, K K; Mufson, E J

    2013-02-01

    Decreases in testosterone and 17β-oestradiol (E(2)) are associated with an increased risk for Alzheimer's disease (AD), which has been attributed to an increase in β-amyloid and tau pathological lesions. Although recent studies have used transgenic animal models to test the effects of sex steroid manipulations on AD-like pathology, almost none have systematically characterised the associations between AD lesions and sex steroid levels in the blood or brain in any mutant model. The present study evaluated age-related changes in testosterone and E(2) concentrations, as well as androgen receptor (AR) and oestrogen receptor (ER) α and β expression, in brain regions displaying AD pathology in intact male and female 3xTgAD and nontransgenic (ntg) mice. We report for the first time that circulating and brain testosterone levels significantly increase in male 3xTgAD mice with age, but without changes in AR-immunoreactive (IR) cell number in the hippocampal CA1 or medial amygdala. The age-related increase in hippocampal testosterone levels correlated positively with increases in the conformational tau isoform, Alz50. These data suggest that the over-expression of human tau up-regulate the hypothalamic-pituitary-gonadal axis in these mice. Although circulating and brain E(2) levels remained stable with age in both male and female 3xTgAD and ntg mice, ER-IR cell number in the hippocampus and medial amygdala decreased with age in female transgenic mice. Furthermore, E(2) levels were significantly higher in the hippocampus than in serum, suggesting local production of E(2). Although triple transgenic mice mimic AD-like pathology, they do not fully replicate changes in human sex steroid levels, and may not be the best model for studying the effects of sex steroids on AD lesions.

  14. Next-Generation A/D Sampler ADS3000+ for VLBI2010

    NASA Technical Reports Server (NTRS)

    Takefuji, Kazuhiro; Takeuchi, Hiroshi; Tsutsumi, Masanori; Koyama, Yasuhiro

    2010-01-01

    A high-speed A/D sampler, called ADS3000+, has been developed in 2008, which can sample one analog signal up to 4 Gbps to versatile Linux PC. After A/D conversion, the ADS3000+ can perform digital signal processing such as real-time DBBC (Digital Base Band Conversion) and FIR filtering such as simple CW RFI filtering using the installed FPGAs. A 4 Gsps fringe test with the ADS3000+ has been successfully performed. The ADS3000+ will not exclusively be used for VLBI but will also be employed in other applications.

  15. Adding flavor to AdS4/CFT3

    NASA Astrophysics Data System (ADS)

    Ammon, Martin; Erdmenger, Johanna; Meyer, René; O'Bannon, Andy; Wrase, Timm

    2009-11-01

    Aharony, Bergman, Jafferis, and Maldacena have proposed that the low-energy description of multiple M2-branes at a Bbb C4/Bbb Zk singularity is a (2+1)-dimensional Script N = 6 supersymmetric U(Nc) × U(Nc) Chern-Simons matter theory, the ABJM theory. In the large-Nc limit, its holographic dual is supergravity in AdS4 × S7/Bbb Zk. We study various ways to add fields that transform in the fundamental representation of the gauge groups, i.e. flavor fields, to the ABJM theory. We work in a probe limit and perform analyses in both the supergravity and field theory descriptions. In the supergravity description we find a large class of supersymmetric embeddings of probe flavor branes. In the field theory description, we present a general method to determine the couplings of the flavor fields to the fields of the ABJM theory. We then study four examples in detail: codimension-zero Script N = 3 supersymmetric flavor, described in supergravity by Kaluza-Klein monopoles or D6-branes; codimension-one Script N = (0,6) supersymmetric chiral flavor, described by D8-branes; codimension-one Script N = (3,3) supersymmetric non-chiral flavor, described by M5/D4-branes; codimension-two Script N = 4 supersymmetric flavor, described by M2/D2-branes. Finally we discuss special physical equivalences between brane embeddings in M-theory, and their interpretation in the field theory description.

  16. Twistor methods for AdS5

    NASA Astrophysics Data System (ADS)

    Adamo, Tim; Skinner, David; Williams, Jack

    2016-08-01

    We consider the application of twistor theory to five-dimensional anti-de Sitter space. The twistor space of AdS5 is the same as the ambitwistor space of the four-dimensional conformal boundary; the geometry of this correspondence is reviewed for both the bulk and boundary. A Penrose transform allows us to describe free bulk fields, with or without mass, in terms of data on twistor space. Explicit representatives for the bulk-to-boundary propagators of scalars and spinors are constructed, along with twistor action functionals for the free theories. Evaluating these twistor actions on bulk-to-boundary propagators is shown to produce the correct two-point functions.

  17. AdS3: the NHEK generation

    NASA Astrophysics Data System (ADS)

    Bena, Iosif; Heurtier, Lucien; Puhm, Andrea

    2016-05-01

    It was argued in [1] that the five-dimensional near-horizon extremal Kerr (NHEK) geometry can be embedded in String Theory as the infrared region of an infinite family of non-supersymmetric geometries that have D1, D5, momentum and KK monopole charges. We show that there exists a method to embed these geometries into asymptotically- {AdS}_3× {S}^3/{{Z}}_N solutions, and hence to obtain infinite families of flows whose infrared is NHEK. This indicates that the CFT dual to the NHEK geometry is the IR fixed point of a Renormalization Group flow from a known local UV CFT and opens the door to its explicit construction.

  18. Sampled sinusoidal stimulation profile and multichannel fuzzy logic classification for monitor-based phase-coded SSVEP brain-computer interfacing

    NASA Astrophysics Data System (ADS)

    Manyakov, Nikolay V.; Chumerin, Nikolay; Robben, Arne; Combaz, Adrien; van Vliet, Marijn; Van Hulle, Marc M.

    2013-06-01

    Objective. The performance and usability of brain-computer interfaces (BCIs) can be improved by new paradigms, stimulation methods, decoding strategies, sensor technology etc. In this study we introduce new stimulation and decoding methods for electroencephalogram (EEG)-based BCIs that have targets flickering at the same frequency but with different phases. Approach. The phase information is estimated from the EEG data, and used for target command decoding. All visual stimulation is done on a conventional (60-Hz) LCD screen. Instead of the ‘on/off’ visual stimulation, commonly used in phase-coded BCI, we propose one based on a sampled sinusoidal intensity profile. In order to fully exploit the circular nature of the evoked phase response, we introduce a filter feature selection procedure based on circular statistics and propose a fuzzy logic classifier designed to cope with circular information from multiple channels jointly. Main results. We show that the proposed visual stimulation enables us not only to encode more commands under the same conditions, but also to obtain EEG responses with a more stable phase. We also demonstrate that the proposed decoding approach outperforms existing ones, especially for the short time windows used. Significance. The work presented here shows how to overcome some of the limitations of screen-based visual stimulation. The superiority of the proposed decoding approach demonstrates the importance of preserving the circularity of the data during the decoding stage.

  19. Shadows, currents, and AdS fields

    SciTech Connect

    Metsaev, R. R.

    2008-11-15

    Conformal totally symmetric arbitrary spin currents and shadow fields in flat space-time of dimension greater than or equal to four are studied. A gauge invariant formulation for such currents and shadow fields is developed. Gauge symmetries are realized by involving the Stueckelberg fields. A realization of global conformal boost symmetries is obtained. Gauge invariant differential constraints for currents and shadow fields are obtained. AdS/CFT correspondence for currents and shadow fields and the respective normalizable and non-normalizable solutions of massless totally symmetric arbitrary spin AdS fields are studied. The bulk fields are considered in a modified de Donder gauge that leads to decoupled equations of motion. We demonstrate that leftover on shell gauge symmetries of bulk fields correspond to gauge symmetries of boundary currents and shadow fields, while the modified de Donder gauge conditions for bulk fields correspond to differential constraints for boundary conformal currents and shadow fields. Breaking conformal symmetries, we find interrelations between the gauge invariant formulation of the currents and shadow fields, and the gauge invariant formulation of massive fields.

  20. Challenges to be overcome using population-based sampling methods to recruit veterans for a study of post-traumatic stress disorder and traumatic brain injury

    PubMed Central

    2014-01-01

    Background Many investigators are interested in recruiting veterans from recent conflicts in Afghanistan and Iraq with Traumatic Brain Injury (TBI) and/or Post Traumatic Stress Disorder (PTSD). Researchers pursuing such studies may experience problems in recruiting sufficient numbers unless effective strategies are used. Currently, there is very little information on recruitment strategies for individuals with TBI and/or PTSD. It is known that groups of patients with medical conditions may be less likely to volunteer for clinical research. This study investigated the feasibility of recruiting veterans returning from recent military conflicts— Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) - using a population-based sampling method. Methods Individuals were sampled from a previous epidemiological study. Three study sites focused on recruiting survey respondents (n = 445) who lived within a 60 mile radius of one of the sites. Results Overall, the successful recruitment of veterans using a population-based sampling method was dependent on the ability to contact potential participants following mass mailing. Study enrollment of participants with probable TBI and/or PTSD had a recruitment yield (enrolled/total identified) of 5.4%. We were able to contact 146 individuals, representing a contact rate of 33%. Sixty-six of the individuals contacted were screened. The major reasons for not screening included a stated lack of interest in the study (n = 37), a failure to answer screening calls after initial contact (n = 30), and an unwillingness or inability to travel to a study site (n = 10). Based on the phone screening, 36 veterans were eligible for the study. Twenty-four veterans were enrolled, (recruitment yield = 5.4%) and twelve were not enrolled for a variety of reasons. Conclusions Our experience with a population-based sampling method for recruitment of recent combat veterans illustrates the challenges encountered

  1. Fortress brain.

    PubMed

    Royall, Donald R

    2013-02-01

    Neurodegenerative diseases are associated with neuronal inclusions, comprised of protein aggregates. In Alzheimer's Disease (AD) and Lewy Body Disease (LBD) such lesions are distributed in a hierarchical retrograde transynaptic spatial pattern. This implies a retrograde transynaptic temporal propagation as well. There can be few explanations for this other than infectious agents (prions and viruses). This suggests that AD and LBD (at least) may have infectious origins. Transynaptic infiltration of the CNS along cranial nerve or other major projections, by one or more infectious agents has important implications. The clinical syndrome and natural history of each neurodegenerative disorder will reflect its portal of entry. There may be a different neurodegenerative syndrome for each cranial nerve or other portal of entry, and not all may manifest as "dementia". Each syndrome may be associated with more than one pathological lesion. Each pathology may be associated with several clinical syndromes. Host-parasite interactions are species specific. This may explain the rarity of AD-like pathology in most other older mammals. Over evolutionary timescales, the human brain should be adapted to predation by neurotropic agents. Viewed from this perspective, the prion-like pro-inflammatory and pro-apoptotic properties of β-amyloid and other proteins may be adaptive, and anti-microbial. Reductions in synaptic density may slow the progress of invading pathogens, while perineuronal nets and other structures may guard the gates. This suggests a defense in depth of a structure, the brain, that is inherently vulnerable to invasion along its neural networks.

  2. BACE1 activity in cerebrospinal fluid and its relation to markers of AD pathology.

    PubMed

    Mulder, Sandra D; van der Flier, Wiesje M; Verheijen, Jan H; Mulder, Cees; Scheltens, Philip; Blankenstein, Marinus A; Hack, C Erik; Veerhuis, Robert

    2010-01-01

    Several studies have shown that reduced amyloid-beta 1-42 (Abeta(42)) and increased tau levels in cerebrospinal fluid (CSF) reflect increased Alzheimer's disease (AD) pathology in the brain. beta-site APP cleaving enzyme (BACE1) is thought to be the major beta-secretase involved in Abeta production in the brain, and therefore we investigated the relation between BACE1 activity and CSF markers Abeta(40), Abeta(42), total tau (t-tau), and tau phosphorylated at threonine 181 (p-tau) in CSF of control (n=12), mild cognitive impairment (n=18), and AD (n=17) subjects. Patients were classified according to their Abeta(42), t-tau, and p-tau CSF biomarker levels, with either an AD-like biomarker profile (two or three biomarkers abnormal: Abeta(42) < 495 pg/ml in combination with t-tau > 356 pg/ml, and/or p-tau > 54 pg/ml) or a normal biomarker profile (AD-like biomarker profile (66 +/- 6 years, 53% female, and Mini-Mental Status Examination (MMSE) score: 23 +/- 5) and 28 subjects with a normal biomarker profile (62 +/- 11 years, 43% female, and MMSE score: 27 +/- 4). Subjects with an AD-like biomarker profile had higher CSF BACE1 activity levels, compared to patients with a normal biomarker profile (20 pg/ml and 16 pg/ml respectively; p=0.01), when controlled for age and gender. In the whole sample, BACE1 activity correlated with CSF levels of Abeta(40), t-tau, and p-tau (r=0.38, r=0.63, and r=0.65; all p< 0.05), but not with Abeta(42). These data suggest that increased BACE1 activity in CSF relates to AD pathology in the brain.

  3. BACE1 activity in cerebrospinal fluid and its relation to markers of AD pathology.

    PubMed

    Mulder, Sandra D; van der Flier, Wiesje M; Verheijen, Jan H; Mulder, Cees; Scheltens, Philip; Blankenstein, Marinus A; Hack, C Erik; Veerhuis, Robert

    2010-01-01

    Several studies have shown that reduced amyloid-beta 1-42 (Abeta(42)) and increased tau levels in cerebrospinal fluid (CSF) reflect increased Alzheimer's disease (AD) pathology in the brain. beta-site APP cleaving enzyme (BACE1) is thought to be the major beta-secretase involved in Abeta production in the brain, and therefore we investigated the relation between BACE1 activity and CSF markers Abeta(40), Abeta(42), total tau (t-tau), and tau phosphorylated at threonine 181 (p-tau) in CSF of control (n=12), mild cognitive impairment (n=18), and AD (n=17) subjects. Patients were classified according to their Abeta(42), t-tau, and p-tau CSF biomarker levels, with either an AD-like biomarker profile (two or three biomarkers abnormal: Abeta(42) < 495 pg/ml in combination with t-tau > 356 pg/ml, and/or p-tau > 54 pg/ml) or a normal biomarker profile (AD-like biomarker profile (66 +/- 6 years, 53% female, and Mini-Mental Status Examination (MMSE) score: 23 +/- 5) and 28 subjects with a normal biomarker profile (62 +/- 11 years, 43% female, and MMSE score: 27 +/- 4). Subjects with an AD-like biomarker profile had higher CSF BACE1 activity levels, compared to patients with a normal biomarker profile (20 pg/ml and 16 pg/ml respectively; p=0.01), when controlled for age and gender. In the whole sample, BACE1 activity correlated with CSF levels of Abeta(40), t-tau, and p-tau (r=0.38, r=0.63, and r=0.65; all p< 0.05), but not with Abeta(42). These data suggest that increased BACE1 activity in CSF relates to AD pathology in the brain. PMID:20164582

  4. Identification of Novel Tau Interactions with Endoplasmic Reticulum Proteins in Alzheimer’s Disease Brain

    PubMed Central

    Meier, Shelby; Bell, Michelle; Lyons, Danielle N.; Ingram, Alexandria; Chen, Jing; Gensel, John C.; Zhu, Haining; Nelson, Peter T.; Abisambra, Jose F.

    2016-01-01

    Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that is pathologically characterized by the formation of extracellular amyloid plaques and intraneuronal tau tangles. We recently identified that tau associates with proteins known to participate in endoplasmic reticulum (ER)-associated degradation (ERAD); consequently, ERAD becomes dysfunctional and causes neurotoxicity. We hypothesized that tau associates with other ER proteins, and that this association could also lead to cellular dysfunction in AD. Portions of human AD and non-demented age matched control brains were fractionated to obtain microsomes, from which tau was co-immunoprecipitated. Samples from both conditions containing tau and its associated proteins were analyzed by mass spectrometry. In total, we identified 91 ER proteins that co-immunoprecipitated with tau; 15.4% were common between AD and control brains, and 42.9% only in the AD samples. The remainder, 41.8% of the proteins, was only seen in the control brain samples. We identified a variety of previously unreported interactions between tau and ER proteins. These proteins participate in over sixteen functional categories, the most abundant being involved in RNA translation. We then determined that association of tau with these ER proteins was different between the AD and control samples. We found that tau associated equally with the ribosomal protein L28 but more robustly with the ribosomal protein P0. These data suggest that the differential association between tau and ER proteins in disease could reveal the pathogenic processes by which tau induces cellular dysfunction. PMID:26402096

  5. Characterizing the Role of Brain Derived Neurotrophic Factor Genetic Variation in Alzheimer’s Disease Neurodegeneration

    PubMed Central

    Honea, Robyn A.; Cruchaga, Carlos; Perea, Rodrigo D.; Saykin, Andrew J.; Burns, Jeffrey M.; Weinberger, Daniel R.; Goate, Alison M.

    2013-01-01

    There is accumulating evidence that neurotrophins, like brain-derived neurotrophic factor (BDNF), may impact aging and Alzheimer’s Disease. However, traditional genetic association studies have not found a clear relationship between BDNF and AD. Our goal was to test whether BDNF single nucleotide polymorphisms (SNPs) impact Alzheimer’s Disease-related brain imaging and cognitive markers of disease. We completed an imaging genetics study on 645 Alzheimer’s Disease Neuroimaging Initiative participants (ND=175, MCI=316, AD=154) who had cognitive, brain imaging, and genetics data at baseline and a subset of those with brain imaging data at two years. Samples were genotyped using the Illumina Human610-Quad BeadChip. 13 SNPs in BDNF were identified in the dataset following quality control measures (rs6265(Val66Met), rs12273363, rs11030094, rs925946, rs1050187, rs2203877, rs11030104, rs11030108, rs10835211, rs7934165, rs908867, rs1491850, rs1157459). We analyzed a subgroup of 8 SNPs that were in low linkage disequilibrium with each other. Automated brain morphometric measures were available through ADNI investigators, and we analyzed baseline cognitive scores, hippocampal and whole brain volumes, and rates of hippocampal and whole brain atrophy and rates of change in the ADAS-Cog over one and two years. Three out of eight BDNF SNPs analyzed were significantly associated with measures of cognitive decline (rs1157659, rs11030094, rs11030108). No SNPs were significantly associated with baseline brain volume measures, however six SNPs were significantly associated with hippocampal and/or whole brain atrophy over two years (rs908867, rs11030094, rs6265, rs10501087, rs1157659, rs1491850). We also found an interaction between the BDNF Val66Met SNP and age with whole brain volume. Our imaging-genetics analysis in a large dataset suggests that while BDNF genetic variation is not specifically associated with a diagnosis of AD, it appears to play a role in AD-related brain

  6. For Uncontrolled Tremor, Ultrasound Instead of Brain Surgery?

    MedlinePlus

    ... failed, doctors could only offer brain surgery -- including deep brain stimulation -- as a potential treatment, the researchers said. Focused ... outcomes were as good as those seen with deep brain stimulation, Tierney added. If the tremor recurs, the procedure ...

  7. ADS pilot program Plan

    NASA Technical Reports Server (NTRS)

    Clauson, J.; Heuser, J.

    1981-01-01

    The Applications Data Service (ADS) is a system based on an electronic data communications network which will permit scientists to share the data stored in data bases at universities and at government and private installations. It is designed to allow users to readily locate and access high quality, timely data from multiple sources. The ADS Pilot program objectives and the current plans for accomplishing those objectives are described.

  8. Brain changes in older adults at very low risk for Alzheimer's disease.

    PubMed

    Fjell, Anders M; McEvoy, Linda; Holland, Dominic; Dale, Anders M; Walhovd, Kristine B

    2013-05-01

    Alzheimer's disease (AD) has a slow onset, so it is challenging to distinguish brain changes in healthy elderly persons from incipient AD. One-year brain changes with a distinct frontotemporal pattern have been shown in older adults. However, it is not clear to what extent these changes may have been affected by undetected, early AD. To address this, we estimated 1-year atrophy by magnetic resonance imaging (MRI) in 132 healthy elderly persons who had remained free of diagnosed mild cognitive impairment or AD for at least 3 years. We found significant volumetric reductions throughout the brain. The sample was further divided into low-risk groups based on clinical, biomarker, genetic, or cognitive criteria. Although sample sizes varied, significant reductions were observed in all groups, with rates and topographical distribution of atrophy comparable to that of the full sample. Volume reductions were especially pronounced in the default mode network, closely matching the previously described frontotemporal pattern of changes in healthy aging. Atrophy in the hippocampus predicted change in memory, with no additional default mode network contributions. In conclusion, reductions in regional brain volumes can be detected over the course of 1 year even in older adults who are unlikely to be in a presymptomatic stage of AD.

  9. Profiles of Alzheimer's disease-related pathology in an aging urban population sample in India.

    PubMed

    Purohit, Dushyant P; Batheja, Nirmala O; Sano, Mary; Jashnani, Kusum D; Kalaria, Rajesh N; Karunamurthy, Arivarasan; Kaur, Shalinder; Shenoy, Asha S; Van Dyk, Kathleen; Schmeidler, James; Perl, Daniel P

    2011-01-01

    Systematic studies on Alzheimer's disease (AD)-related pathology that complement clinical and epidemiological data on dementia from low and middle income countries are rare. We report the first large study on AD-related pathology in autopsy service-derived brains from an urban center in India, a low/middle income country, and compare findings with a similar sample from New York. Amyloid-β plaques and neurofibrillary tangles were assessed in 91 brain specimens derived from hospital autopsy cases from Mumbai, India (age 60+ years; mean age 71.1 years, ± 8.3 SD; range 60-107 years) and compared with identically examined age-matched sample obtained in New York. These cases had no known clinical history of dementia. Our study showed that in comparison with the New York sample, the mean brain weight of the Mumbai sample was lower (p = 0.013) and mean diffuse plaque density was higher (p = 0.019), while differences in mean density and counts of neurofibrillary tangles and neuritic plaques were not statistically significant (p > 0.05). Our findings indicate that the burden of AD-related pathology was approximately equivalent in Mumbai and New York samples, which is at variance with expected lower AD-related lesion burden based on the clinical/epidemiological studies suggesting lower prevalence of AD in India.

  10. Reduced sample sizes for atrophy outcomes in Alzheimer's disease trials: baseline adjustment.

    PubMed

    Schott, J M; Bartlett, J W; Barnes, J; Leung, K K; Ourselin, S; Fox, N C

    2010-08-01

    Cerebral atrophy rate is increasingly used as an outcome measure for Alzheimer's disease (AD) trials. We used the Alzheimer's disease Neuroimaging initiative (ADNI) dataset to assess if adjusting for baseline characteristics can reduce sample sizes. Controls (n = 199), patients with mild cognitive impairment (MCI) (n = 334) and AD (n = 144) had two MRI scans, 1-year apart; approximately 55% had baseline CSF tau, p-tau, and Abeta1-42. Whole brain (KN-BSI) and hippocampal (HMAPS-HBSI) atrophy rate, and ventricular expansion (VBSI) were calculated for each group; numbers required to power a placebo-controlled trial were estimated. Sample sizes per arm (80% power, 25% absolute rate reduction) for AD were (95% CI): brain atrophy = 81 (64,109), hippocampal atrophy = 88 (68,119), ventricular expansion = 118 (92,157); and for MCI: brain atrophy = 149 (122,188), hippocampal atrophy = 201 (160,262), ventricular expansion = 234 (191,295). To detect a 25% reduction relative to normal aging required increased sample sizes approximately 3-fold (AD), and approximately 5-fold (MCI). Disease severity and Abeta1-42 contributed significantly to atrophy rate variability. Adjusting for 11 predefined covariates reduced sample sizes by up to 30%. Treatment trials in AD should consider the effects of normal aging; adjusting for baseline characteristics can significantly reduce required sample sizes.

  11. Functional Brain Imaging

    PubMed Central

    2006-01-01

    Database of Systematic Reviews, CENTRAL, and International Network of Agencies for Health Technology Assessment (INAHTA). The database search was supplemented with a search of relevant Web sites and a review of the bibliographies of selected papers. General inclusion criteria were applied to all conditions. Those criteria included the following: Full reports of systematic reviews, randomized controlled trials (RCTs), cohort-control studies, prospective cohort studies (PCS’), and retrospective studies. Sample sizes of at least 20 patients (≥ 10 with condition being reviewed). English-language studies. Human studies. Any age. Studying at least one of the following: fMRI, PET, MRS, or MEG. Functional brain imaging modality must be compared with a clearly defined reference standard. Must report at least one of the following outcomes: sensitivity, specificity, accuracy, positive predictive value (PPV), receiver operating characteristic curve, outcome measuring impact on diagnostic testing, treatment, patient health, or cost. Summary of Findings There is evidence to indicate that PET can accurately diagnose AD; however, at this time, there is no evidence to suggest that a diagnosis of AD with PET alters the clinical outcomes of patients. The addition of MRS or O-(2-18F-Fluoroethyl)-L-Tyrosine (FET)-PET to gadolinium (Gd)-enhanced MRI for distinguishing malignant from benign tumours during primary diagnosis may provide a higher specificity than Gd-enhanced MRI alone. The clinical utility of additional imaging in patients to distinguish malignant from benign tumours is unclear, because patients with a suspected brain tumour will likely undergo a biopsy despite additional imaging results. The addition of MRS, FET-PET, or MRI T2 to Gd-enhanced MRI for the differentiation of recurrence from radiation necrosis may provide a higher specificity than Gd-enhanced MRI alone. The clinical utility of additional imaging in patients with a suspected recurrence is in the monitoring of

  12. The miR-137 schizophrenia susceptibility variant rs1625579 does not predict variability in brain volume in a sample of schizophrenic patients and healthy individuals.

    PubMed

    Rose, Emma J; Morris, Derek W; Fahey, Ciara; Cannon, Dara; McDonald, Colm; Scanlon, Cathy; Kelly, Sinead; Gill, Michael; Corvin, Aiden; Donohoe, Gary

    2014-09-01

    The micro RNA 137 (miR-137) variant rs1625579 has been identified as a genome-wide significant risk variant for schizophrenia. miR-137 has an established role in neurodevelopment and may mediate cognitive dysfunction in schizophrenia. This role of miR-137 may be related to changes in brain morphology for risk-related genotypes; however this has not yet been delineated. Here we considered whether rs1625579 genotype was predictive of indices of brain structure in patients with schizophrenia and healthy controls. Structural magnetic resonance imaging (sMRI) data (i.e. 3T T1-TFE or 1.5T T1-MPRAGE) were acquired from 150 healthy controls and 163 schizophrenic patients. Two volumetric analyses that considered the impact of miR-137/rs1625579 genotype were carried out on sMRI data. In the first analysis, voxel based morphometry was employed to consider genotype-related variability in local grey and white matter across the entire brain volume. Our secondary analysis utilized the FIRST protocol in FSL to consider the volume of subcortical structures (i.e. bilateral accumbens, amygdala, caudate, hippocampus, pallidum, putamen and thalamus). Several brain regions in both analyses demonstrated the expected main effect of participant group (i.e. schizophrenics < controls), yet there were no regions where we observed an impact of rs1635579 genotype on brain volume. Our analyses suggest that the mechanism by which miR-137 confers risk for schizophrenia and impacts upon cognitive function may not be mediated by changes in local brain volume. However, it remains to be determined whether or not alternative measures of brain structure are related to these functions of miR-137. PMID:25044277

  13. A Preliminary Study of the Effects of an Arts Education Program on Executive Function, Behavior, and Brain Structure in a Sample of Nonclinical School-Aged Children.

    PubMed

    Park, Subin; Lee, Jong-Min; Baik, Young; Kim, Kihyun; Yun, Hyuk Jin; Kwon, Hunki; Jung, Yeon-Kyung; Kim, Bung-Nyun

    2015-11-01

    The authors examined the effects of arts education on cognition, behavior, and brain of children. Twenty-nine nonclinical children participated in a 15-week arts education program that was composed of either creative movement or musical arts. Children completed the Wisconsin Card Sorting Test, clinical scales, and brain magnetic resonance imaging before and after the intervention. Following program completion, performances on the Wisconsin Card Sorting Test, the Children's Depression Inventory scores, and conduct disorder scores were significantly improved. Furthermore, cortical thickness in the left postcentral gyrus and superior parietal lobule were increased, and the mean diffusivity values in the right posterior corona radiate and superior longitudinal fasciculus were decreased. Positive correlations between changes in cognitive measurements and changes in cortical thickness were observed. This preliminary study suggests a positive effect of arts education on executive functions in association with brain changes. However, these findings must be interpreted with caution due to the noncomparative study design.

  14. What Value "Value Added"?

    ERIC Educational Resources Information Center

    Richards, Andrew

    2015-01-01

    Two quantitative measures of school performance are currently used, the average points score (APS) at Key Stage 2 and value-added (VA), which measures the rate of academic improvement between Key Stage 1 and 2. These figures are used by parents and the Office for Standards in Education to make judgements and comparisons. However, simple…

  15. Brain herniation

    MedlinePlus

    ... herniation; Uncal herniation; Subfalcine herniation; Tonsillar herniation; Herniation - brain ... Brain herniation occurs when something inside the skull produces pressure that moves brain tissues. This is most ...

  16. Introducing ADS Labs

    NASA Astrophysics Data System (ADS)

    Accomazzi, Alberto; Henneken, E.; Grant, C. S.; Kurtz, M. J.; Di Milia, G.; Luker, J.; Thompson, D. M.; Bohlen, E.; Murray, S. S.

    2011-05-01

    ADS Labs is a platform that ADS is introducing in order to test and receive feedback from the community on new technologies and prototype services. Currently, ADS Labs features a new interface for abstract searches, faceted filtering of results, visualization of co-authorship networks, article-level recommendations, and a full-text search service. The streamlined abstract search interface provides a simple, one-box search with options for ranking results based on a paper relevancy, freshness, number of citations, and downloads. In addition, it provides advanced rankings based on collaborative filtering techniques. The faceted filtering interface allows users to narrow search results based on a particular property or set of properties ("facets"), allowing users to manage large lists and explore the relationship between them. For any set or sub-set of records, the co-authorship network can be visualized in an interactive way, offering a view of the distribution of contributors and their inter-relationships. This provides an immediate way to detect groups and collaborations involved in a particular research field. For a majority of papers in Astronomy, our new interface will provide a list of related articles of potential interest. The recommendations are based on a number of factors, including text similarity, citations, and co-readership information. The new full-text search interface allows users to find all instances of particular words or phrases in the body of the articles in our full-text archive. This includes all of the scanned literature in ADS as well as a select portion of the current astronomical literature, including ApJ, ApJS, AJ, MNRAS, PASP, A&A, and soon additional content from Springer journals. Fulltext search results include a list of the matching papers as well as a list of "snippets" of text highlighting the context in which the search terms were found. ADS Labs is available at http://adslabs.org

  17. Brain perfusion correlates of visuoperceptual deficits in Mild Cognitive Impairment and mild Alzheimer’s disease

    PubMed Central

    Alegret, Montserrat; Vinyes-Junqué, Georgina; Boada, Mercè; Martínez-Lage, Pablo; Cuberas, Gemma; Espinosa, Ana; Roca, Isabel; Hernández, Isabel; Valero, Sergi; Rosende-Roca, Maitée; Mauleón, Ana; Becker, James T.; Tárraga, Lluís

    2012-01-01

    Background Visuoperceptual processing is impaired early in the clinical course of Alzheimer’s disease (AD). The 15-Objects Test (15-OT) detects such subtle performance deficits in Mild Cognitive Impairment (MCI) and mild AD. Reduced brain perfusion in the temporal, parietal and prefrontal regions have been found in early AD and MCI patients. Objectives To confirm the role of the 15-OT in the diagnosis of MCI and AD, and to investigate the brain perfusion correlates of visuoperceptual dysfunction (15-OT) in subjects with MCI, AD and normal aging. Methods Forty-two AD, 42 MCI and 42 healthy elderly control (EC) subjects underwent a brain Single Photon Emission Tomography (SPECT) and separately completed the 15-OT. An analysis of variance compared 15-OT scores between groups. SPM5 was used to analyse the SPECT data. Results 15-OT performace was impaired in the MCI and AD patients. In terms of the SPECT scans, AD patients showed reduced perfusion in temporal-parietal regions, while the MCI subjects had decreased perfusion in the middle and posterior cingulate. When MCI and AD groups were compared, a significant brain perfusion reduction was found in temporo-parietal regions. In the whole sample, 15-OT performance was significantly correlated with the clinical dementia rating scores, and with the perfusion in the bilateral posterior cingulate and the right temporal pole, with no significant correlation in each separate group. Conclusion Our findings suggest that the 15-OT performance provides a useful gradation of impairment from normal aging to AD, and it seems to be related to perfusion in the bilateral posterior cingulate and the right temporal pole. PMID:20555146

  18. Raft disorganization leads to reduced plasmin activity in Alzheimer's disease brains.

    PubMed

    Ledesma, Maria Dolores; Abad-Rodriguez, José; Galvan, Cristian; Biondi, Elisa; Navarro, Pilar; Delacourte, Andre; Dingwall, Colin; Dotti, Carlos G

    2003-12-01

    The serine protease plasmin can efficiently degrade amyloid peptide in vitro, and is found at low levels in the hippocampus of patients with Alzheimer's disease (AD). The cause of such paucity remains unknown. We show here that the levels of total brain plasminogen and plasminogen-binding molecules are normal in these brain samples, yet plasminogen membrane binding is greatly reduced. Biochemical analysis reveals that the membranes of these brains have a mild, still significant, cholesterol reduction compared to age-matched controls, and anomalous raft microdomains. This was reflected by the loss of raft-enriched proteins, including plasminogen-binding and -activating molecules. Using hippocampal neurons in culture, we demonstrate that removal of a similar amount of membrane cholesterol is sufficient to induce raft disorganization, leading to reduced plasminogen membrane binding and low plasmin activity. These results suggest that brain raft alterations may contribute to AD by rendering the plasminogen system inefficient.

  19. Adding stress plot function to NASTRAN

    NASA Technical Reports Server (NTRS)

    Katoh, S.

    1978-01-01

    Stress plot function was developed and added to the NASTRAN level 15.5. Computed stress distribution can be displayed by this function, with vectors showing the principal stresses of the finite elements over the specified portions of the structure. NASTRAN is reviewed in the aspect of plotting capabilities. Stress tensor field is examined in preparation of stress display. Then the stress plot function as added to the NASTRAN is described. A sample plotout by this function is shown.

  20. The Added Value of the Combined Use of the Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule: Diagnostic Validity in a Clinical Swedish Sample of Toddlers and Young Preschoolers

    ERIC Educational Resources Information Center

    Zander, Eric; Sturm, Harald; Bölte, Sven

    2015-01-01

    The diagnostic validity of the new research algorithms of the Autism Diagnostic Interview-Revised and the revised algorithms of the Autism Diagnostic Observation Schedule was examined in a clinical sample of children aged 18-47 months. Validity was determined for each instrument separately and their combination against a clinical consensus…

  1. Segmentation and quantification for Alzheimer's disease (AD): a preliminary study

    NASA Astrophysics Data System (ADS)

    Lei, Tianhu; Udupa, Jayaram K.; Zhuge, Ying; Moonis, Gul; Clark, Christopher

    2003-05-01

    Alzheimer's is a progressive brain disease and is clinically characterized by cognitive symptoms that, in combination with behavioral disturbances, significantly interfere with activities of daily living. The purpose of this study is to investigate the possibility of developing volumetric measures of the structural damage and atrophy of brain derived from multiprotocol MR imaging. Our approach first applies intensity inhomogeneity correction and intensity standardization to PD and T2 weighted MR images to create base images for quantitative image analysis. Then, vectorial scale-based fuzzy connectedness segmentation (VSFCS) and morphological operations are applied to the base images to extract masks of cerebrospinal fluid (CSF), grey matter (GM), and white matter (WM), and further to create a clean and accurate intracranial (IC) mask. After separating CSF from brain parenchyma (BP), VSFCS is applied to BP (PD and T2) images to generate pure GM and WM masks, and then subtracting these pure from the BP mask to detect AD lesions. This method was applied to a set of conventional PD and T2 weighted MR images that were obtained from 5 patients with probable AD and 5 healthy normal control subjects. The segmented images of individual brain tissue regions (CSF, GM, WM, and AD lesion) are consistent with a Neuroradiologist's examination. The quantitative analysis shows that patients with AD have more atrophy. The mean value of the volume of brain parenchyma of patients with AD is about 10% less than that of healthy controls.

  2. Lunar Sample Compendium

    NASA Technical Reports Server (NTRS)

    Meyer, C.

    2009-01-01

    The Lunar Sample Compendium is a succinct summary of what has been learned from the study of Apollo and Luna samples of the Moon. Basic information is compiled, sample-by-sample, in the form of an advanced catalog in order to provide a basic description of each sample. Information presented is carefully attributed to the original source publication, thus the Compendium also serves as a ready access to the now vast scientific literature pertaining to lunar smples. The Lunar Sample Compendium is a work in progress (and may always be). Future plans include: adding sections on additional samples, adding new thin section photomicrographs, replacing the faded photographs with newly digitized photos from the original negatives, attempting to correct the age data using modern decay constants, adding references to each section, and adding an internal search engine.

  3. Two Virasoro symmetries in stringy warped AdS3

    NASA Astrophysics Data System (ADS)

    Compère, Geoffrey; Guica, Monica; Rodriguez, Maria J.

    2014-12-01

    We study three-dimensional consistent truncations of type IIB supergravity which admit warped AdS3 solutions. These theories contain subsectors that have no bulk dynamics. We show that the symplectic form for these theories, when restricted to the non-dynamical subsectors, equals the symplectic form for pure Einstein gravity in AdS3. Consequently, for each consistent choice of boundary conditions in AdS3, we can define a consistent phase space in warped AdS3 with identical conserved charges. This way, we easily obtain a Virasoro × Virasoro asymptotic symmetry algebra in warped AdS3; two different types of Virasoro × Kač-Moody symmetries are also consistent alternatives.

  4. Leading Change, Adding Value.

    PubMed

    Evans, Nick

    2016-09-12

    Essential facts Leading Change, Adding Value is NHS England's new nursing and midwifery framework. It is designed to build on Compassion in Practice (CiP), which was published 3 years ago and set out the 6Cs: compassion, care, commitment, courage, competence and communication. CiP established the values at the heart of nursing and midwifery, while the new framework sets out how staff can help transform the health and care sectors to meet the aims of the NHS England's Five Year Forward View. PMID:27615573

  5. Plasma clusterin concentration is associated with longitudinal brain atrophy in mild cognitive impairment.

    PubMed

    Thambisetty, Madhav; An, Yang; Kinsey, Anna; Koka, Deepthi; Saleem, Muzamil; Güntert, Andreas; Kraut, Michael; Ferrucci, Luigi; Davatzikos, Christos; Lovestone, Simon; Resnick, Susan M

    2012-01-01

    Recent genetic and proteomic studies demonstrate that clusterin/apolipoprotein-J is associated with risk, pathology, and progression of Alzheimer's disease (AD). Our main aim was to examine associations between plasma clusterin concentration and longitudinal changes in brain volume in normal aging and mild cognitive impairment (MCI). A secondary objective was to examine associations between peripheral concentration of clusterin and its concentration in the brain within regions that undergo neuropathological changes in AD. Non-demented individuals (N=139; mean baseline age 70.5 years) received annual volumetric MRI (912 MRI scans in total) over a mean six-year interval. Sixteen participants (92 MRI scans in total) were diagnosed during the course of the study with amnestic MCI. Clusterin concentration was assayed by ELISA in plasma samples collected within a year of the baseline MRI. Mixed effects regression models investigated whether plasma clusterin concentration was associated with rates of brain atrophy for control and MCI groups and whether these associations differed between groups. In a separate autopsy sample of individuals with AD (N=17) and healthy controls (N=4), we examined the association between antemortem clusterin concentration in plasma and postmortem levels in the superior temporal gyrus, hippocampus and cerebellum. The associations of plasma clusterin concentration with rates of change in brain volume were significantly different between MCI and control groups in several volumes including whole brain, ventricular CSF, temporal gray matter as well as parahippocampal, superior temporal and cingulate gyri. Within the MCI but not control group, higher baseline concentration of plasma clusterin was associated with slower rates of brain atrophy in these regions. In the combined autopsy sample of AD and control cases, representing a range of severity in AD pathology, we observed a significant association between clusterin concentration in the plasma and

  6. Identification of Differentially Expressed Genes through Integrated Study of Alzheimer’s Disease Affected Brain Regions

    PubMed Central

    Berretta, Regina; Moscato, Pablo

    2016-01-01

    Background Alzheimer’s disease (AD) is the most common form of dementia in older adults that damages the brain and results in impaired memory, thinking and behaviour. The identification of differentially expressed genes and related pathways among affected brain regions can provide more information on the mechanisms of AD. In the past decade, several studies have reported many genes that are associated with AD. This wealth of information has become difficult to follow and interpret as most of the results are conflicting. In that case, it is worth doing an integrated study of multiple datasets that helps to increase the total number of samples and the statistical power in detecting biomarkers. In this study, we present an integrated analysis of five different brain region datasets and introduce new genes that warrant further investigation. Methods The aim of our study is to apply a novel combinatorial optimisation based meta-analysis approach to identify differentially expressed genes that are associated to AD across brain regions. In this study, microarray gene expression data from 161 samples (74 non-demented controls, 87 AD) from the Entorhinal Cortex (EC), Hippocampus (HIP), Middle temporal gyrus (MTG), Posterior cingulate cortex (PC), Superior frontal gyrus (SFG) and visual cortex (VCX) brain regions were integrated and analysed using our method. The results are then compared to two popular meta-analysis methods, RankProd and GeneMeta, and to what can be obtained by analysing the individual datasets. Results We find genes related with AD that are consistent with existing studies, and new candidate genes not previously related with AD. Our study confirms the up-regualtion of INFAR2 and PTMA along with the down regulation of GPHN, RAB2A, PSMD14 and FGF. Novel genes PSMB2, WNK1, RPL15, SEMA4C, RWDD2A and LARGE are found to be differentially expressed across all brain regions. Further investigation on these genes may provide new insights into the development of AD

  7. Nonlinear realization of local symmetries of AdS space

    SciTech Connect

    Clark, T.E.; Love, S.T.; Nitta, Muneto; Veldhuis, T. ter

    2005-10-15

    Coset methods are used to construct the action describing the dynamics associated with the spontaneous breaking of the local symmetries of AdS{sub d+1} space due to the embedding of an AdS{sub d} brane. The resulting action is an SO(2,d) invariant AdS form of the Einstein-Hilbert action, which in addition to the AdS{sub d} gravitational vielbein, also includes a massive vector field localized on the brane. Its long wavelength dynamics is the same as a massive Abelian vector field coupled to gravity in AdS{sub d} space.

  8. Latent feature representation with stacked auto-encoder for AD/MCI diagnosis.

    PubMed

    Suk, Heung-Il; Lee, Seong-Whan; Shen, Dinggang

    2015-03-01

    Recently, there have been great interests for computer-aided diagnosis of Alzheimer's disease (AD) and its prodromal stage, mild cognitive impairment (MCI). Unlike the previous methods that considered simple low-level features such as gray matter tissue volumes from MRI, and mean signal intensities from PET, in this paper, we propose a deep learning-based latent feature representation with a stacked auto-encoder (SAE). We believe that there exist latent non-linear complicated patterns inherent in the low-level features such as relations among features. Combining the latent information with the original features helps build a robust model in AD/MCI classification, with high diagnostic accuracy. Furthermore, thanks to the unsupervised characteristic of the pre-training in deep learning, we can benefit from the target-unrelated samples to initialize parameters of SAE, thus finding optimal parameters in fine-tuning with the target-related samples, and further enhancing the classification performances across four binary classification problems: AD vs. healthy normal control (HC), MCI vs. HC, AD vs. MCI, and MCI converter (MCI-C) vs. MCI non-converter (MCI-NC). In our experiments on ADNI dataset, we validated the effectiveness of the proposed method, showing the accuracies of 98.8, 90.7, 83.7, and 83.3 % for AD/HC, MCI/HC, AD/MCI, and MCI-C/MCI-NC classification, respectively. We believe that deep learning can shed new light on the neuroimaging data analysis, and our work presented the applicability of this method to brain disease diagnosis.

  9. Dressing phases of AdS3/CFT2

    NASA Astrophysics Data System (ADS)

    Borsato, Riccardo; Ohlsson Sax, Olof; Sfondrini, Alessandro; Stefański, Bogdan, Jr.; Torrielli, Alessandro

    2013-09-01

    We determine the all-loop dressing phases of the AdS3/CFT2 integrable system related to type IIB string theory on AdS3×S3×T4 by solving the recently found crossing relations and studying their singularity structure. The two resulting phases present a novel structure with respect to the ones appearing in AdS5/CFT4 and AdS4/CFT3. In the strongly coupled regime, their leading order reduces to the universal Arutyunov-Frolov-Staudacher phase as expected. We also compute their subleading order and compare it with recent one-loop perturbative results and comment on their weak-coupling expansion.

  10. Bubbling geometries for AdS2× S2

    NASA Astrophysics Data System (ADS)

    Lunin, Oleg

    2015-10-01

    We construct BPS geometries describing normalizable excitations of AdS2×S2. All regular horizon-free solutions are parameterized by two harmonic functions in R 3 with sources along closed curves. This local structure is reminiscent of the "bubbling solutions" for the other AdS p ×S q cases, however, due to peculiar asymptotic properties of AdS2, one copy of R 3 does not cover the entire space, and we discuss the procedure for analytic continuation, which leads to a nontrivial topological structure of the new geometries. We also study supersymmetric brane probes on the new geometries, which represent the AdS2×S2 counterparts of the giant gravitons.

  11. Brain Tumors

    MedlinePlus

    A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are ...

  12. [Value-Added--Adding Economic Value in the Food Industry].

    ERIC Educational Resources Information Center

    Welch, Mary A., Ed.

    1989-01-01

    This booklet focuses on the economic concept of "value added" to goods and services. A student activity worksheet illustrates how the steps involved in processing food are examples of the concept of value added. The booklet further links food processing to the idea of value added to the Gross National Product (GNP). Discussion questions, a student…

  13. Increased O-GlcNAc Levels Correlate with Decreased O-GlcNAcase Levels in Alzheimer Disease Brain

    PubMed Central

    Förster, Sarah; Welleford, Andrew S.; Triplett, Judy C.; Sultana, Rukhsana; Schmitz, Brigitte; Butterfield, D. Allan

    2014-01-01

    The potential role of the posttranslational modification of proteins with O-linked N-acetyl-β-D-glucosamine (O-GlcNAc) in the pathogenesis of Alzheimer disease (AD) has been studied extensively, yet the exact function of O-GlcNAc in AD remains elusive. O-GlcNAc cycling is facilitated by only two highly conserved enzymes: O-GlcNAc transferase (OGT) catalyzes the addition, while O-GlcNAcase (OGA) catalyzes the removal of GlcNAc from proteins. Studies analyzing global O-GlcNAc levels in AD brain have produced inconsistent results and the reasons for altered O-GlcNAcylation in AD are still poorly understood. In this study, we show a 1.2 fold increase in cytosolic protein O-GlcNAc modification in AD brain when compared to age-matched controls. Interestingly, O-GlcNAc changes seem to be attributable to differential modification of a few individual proteins. While our finding of augmented O-GlcNAcylation concurs with some reports, it is contrary to others demonstrating decreased O-GlcNAc levels in AD brain. These conflicting results emphasize the need for further studies providing conclusive evidence on the subject of O-GlcNAcylation in AD. We further demonstrate that, while OGT protein levels are unaffected in AD, OGA protein levels are significantly decreased to 75 % of those in control samples. In addition, augmented protein O-GlcNAc modification correlates to decreased OGA protein levels in AD subjects. While OGA inhibitors are already being tested for AD treatment, our results provide a strong indication that the general subject of O-GlcNAcylation and specifically its regulation by OGA and OGT in AD need further investigation to conclusively elucidate its potential role in AD pathogenesis and treatment. PMID:24859566

  14. Brain surgery

    MedlinePlus

    Craniotomy; Surgery - brain; Neurosurgery; Craniectomy; Stereotactic craniotomy; Stereotactic brain biopsy; Endoscopic craniotomy ... cut depends on where the problem in the brain is located. The surgeon creates a hole in ...

  15. Brain Malformations

    MedlinePlus

    Most brain malformations begin long before a baby is born. Something damages the developing nervous system or causes it ... medicines, infections, or radiation during pregnancy interferes with brain development. Parts of the brain may be missing, ...

  16. Action growth for AdS black holes

    NASA Astrophysics Data System (ADS)

    Cai, Rong-Gen; Ruan, Shan-Ming; Wang, Shao-Jiang; Yang, Run-Qiu; Peng, Rong-Hui

    2016-09-01

    Recently a Complexity-Action (CA) duality conjecture has been proposed, which relates the quantum complexity of a holographic boundary state to the action of a Wheeler-DeWitt (WDW) patch in the anti-de Sitter (AdS) bulk. In this paper we further investigate the duality conjecture for stationary AdS black holes and derive some exact results for the growth rate of action within the Wheeler-DeWitt (WDW) patch at late time approximation, which is supposed to be dual to the growth rate of quantum complexity of holographic state. Based on the results from the general D-dimensional Reissner-Nordström (RN)-AdS black hole, rotating/charged Bañados-Teitelboim-Zanelli (BTZ) black hole, Kerr-AdS black hole and charged Gauss-Bonnet-AdS black hole, we present a universal formula for the action growth expressed in terms of some thermodynamical quantities associated with the outer and inner horizons of the AdS black holes. And we leave the conjecture unchanged that the stationary AdS black hole in Einstein gravity is the fastest computer in nature.

  17. MRI-based brain atrophy rates in ADNI phase 2: acceleration and enrichment considerations for clinical trials.

    PubMed

    Hua, Xue; Ching, Christopher R K; Mezher, Adam; Gutman, Boris A; Hibar, Derrek P; Bhatt, Priya; Leow, Alex D; Jack, Clifford R; Bernstein, Matt A; Weiner, Michael W; Thompson, Paul M

    2016-01-01

    The goal of this work was to assess statistical power to detect treatment effects in Alzheimer's disease (AD) clinical trials using magnetic resonance imaging (MRI)-derived brain biomarkers. We used unbiased tensor-based morphometry (TBM) to analyze n = 5,738 scans, from Alzheimer's Disease Neuroimaging Initiative 2 participants scanned with both accelerated and nonaccelerated T1-weighted MRI at 3T. The study cohort included 198 healthy controls, 111 participants with significant memory complaint, 182 with early mild cognitive impairment (EMCI) and 177 late mild cognitive impairment (LMCI), and 155 AD patients, scanned at screening and 3, 6, 12, and 24 months. The statistical power to track brain change in TBM-based imaging biomarkers depends on the interscan interval, disease stage, and methods used to extract numerical summaries. To achieve reasonable sample size estimates for potential clinical trials, the minimal scan interval was 6 months for LMCI and AD and 12 months for EMCI. TBM-based imaging biomarkers were not sensitive to MRI scan acceleration, which gave results comparable with nonaccelerated sequences. ApoE status and baseline amyloid-beta positron emission tomography data improved statistical power. Among healthy, EMCI, and LMCI participants, sample size requirements were significantly lower in the amyloid+/ApoE4+ group than for the amyloid-/ApoE4- group. ApoE4 strongly predicted atrophy rates across brain regions most affected by AD, but the remaining 9 of the top 10 AD risk genes offered no added predictive value in this cohort.

  18. Superstring theory in AdS(3) and plane waves

    NASA Astrophysics Data System (ADS)

    Son, John Sang Won

    This thesis is devoted to the study of string theory in AdS 3 and its applications to recent developments in string theory. The difficulties associated with formulating a consistent string theory in AdS3 and its underlying SL(2, R) WZW model are explained. We describe how these difficulties can be overcome by assuming that the SL(2, R) WZW model contains spectral flow symmetry. The existence of spectral flow symmetry in the fully quantum treatment is proved by a calculation of the one-loop string partition function. We consider Euclidean AdS 3 with the time direction periodically identified, and compute the torus partition function in this background. The string spectrum can be reproduced by viewing the one-loop calculation as the free energy of a gas of strings, thus providing a rigorous proof of the results based on spectral flow arguments. Next, we turn to spacetimes that are quotients of AdS 3, which include the BTZ black hole and conical spaces. Strings propagating in the conical space are described by taking an orbifold of strings in AdS3. We show that the twisted states of these orbifolds can be obtained by fractional spectral flow. We show that the shift in the ground state energy usually associated with orbifold twists is absent in this case, and offer a unified framework in which to view spectral flow. Lastly, we consider the RNS superstrings in AdS 3 x S3 x M , where M may be K3 or T 4, based on supersymmetric extensions of SL(2, R) and SU(2) WZW models. We construct the physical states and calculate the spectrum. A subsector of this theory describes strings propagating in the six dimensional plane wave obtained by the Penrose limit of AdS3 x S3 x M . We reproduce the plane wave spectrum by taking J and the radius to infinity. We show that the plane wave spectrum actually coincides with the large J spectrum at fixed radius, i.e. in AdS3 x S3. Relation to some recent topics of interest such as the Frolov-Tseytlin string and strings with critical tension

  19. Visualisation of Microglia with the use of Immunohistochemical Double Staining Method for CD-68 and Iba-1 of Cerebral Tissue Samples in Cases of Brain Contusions.

    PubMed

    Stankov, Aleksandar; Belakaposka-Srpanova, Viktorija; Bitoljanu, Natasa; Cakar, Ljupco; Cakar, Zdravko; Rosoklija, Gorazd

    2015-01-01

    In the recent years it has been confirmed that the main component of the immune response in an injury of the nerve cell comes from microglia and macrophages. The main challenge in the field of microglia research is to detect the different stages of cellular activation by visualization of the cell morphology. The existing visualization techniques are based on surface molecules expression in resting and activated microglia cells. For visualization of the microglial cells and their functional state we used double labeling method for cd-68 and iba1 in brain contusions with different survival time. Microglia are stained brown with Iba-1, whereas microglia impregnated with black, grainy color, represents activated microglia stained with CD 68. We had significantly positive results, and we were able to observe changes in the morphology of the microglia that correlated with the survival time. Using double labeling with Iba-1 and cd68 we were able to determine their physiological state based on the morphology and immunoreactivity. PMID:27442380

  20. Entanglement entropy for free scalar fields in AdS

    NASA Astrophysics Data System (ADS)

    Sugishita, Sotaro

    2016-09-01

    We compute entanglement entropy for free massive scalar fields in anti-de Sitter (AdS) space. The entangling surface is a minimal surface whose boundary is a sphere at the boundary of AdS. The entropy can be evaluated from the thermal free energy of the fields on a topological black hole by using the replica method. In odd-dimensional AdS, exact expressions of the Rényi entropy S n are obtained for arbitrary n. We also evaluate 1-loop corrections coming from the scalar fields to holographic entanglement entropy. Applying the results, we compute the leading difference of entanglement entropy between two holographic CFTs related by a renormalization group flow triggered by a double trace deformation. The difference is proportional to the shift of a central charge under the flow.

  1. Asymptotically AdS spacetimes with a timelike Kasner singularity

    NASA Astrophysics Data System (ADS)

    Ren, Jie

    2016-07-01

    Exact solutions to Einstein's equations for holographic models are presented and studied. The IR geometry has a timelike cousin of the Kasner singularity, which is the less generic case of the BKL (Belinski-Khalatnikov-Lifshitz) singularity, and the UV is asymptotically AdS. This solution describes a holographic RG flow between them. The solution's appearance is an interpolation between the planar AdS black hole and the AdS soliton. The causality constraint is always satisfied. The entanglement entropy and Wilson loops are discussed. The boundary condition for the current-current correlation function and the Laplacian in the IR is examined. There is no infalling wave in the IR, but instead, there is a normalizable solution in the IR. In a special case, a hyperscaling-violating geometry is obtained after a dimensional reduction.

  2. New massive gravity and AdS(4) counterterms.

    PubMed

    Jatkar, Dileep P; Sinha, Aninda

    2011-04-29

    We show that the recently proposed Dirac-Born-Infeld extension of new massive gravity emerges naturally as a counterterm in four-dimensional anti-de Sitter space (AdS(4)). The resulting on-shell Euclidean action is independent of the cutoff at zero temperature. We also find that the same choice of counterterm gives the usual area law for the AdS(4) Schwarzschild black hole entropy in a cutoff-independent manner. The parameter values of the resulting counterterm action correspond to a c=0 theory in the context of the duality between AdS(3) gravity and two-dimensional conformal field theory. We rewrite this theory in terms of the gauge field that is used to recast 3D gravity as a Chern-Simons theory. PMID:21635026

  3. Detailed ultraviolet asymptotics for AdS scalar field perturbations

    NASA Astrophysics Data System (ADS)

    Evnin, Oleg; Jai-akson, Puttarak

    2016-04-01

    We present a range of methods suitable for accurate evaluation of the leading asymptotics for integrals of products of Jacobi polynomials in limits when the degrees of some or all polynomials inside the integral become large. The structures in question have recently emerged in the context of effective descriptions of small amplitude perturbations in anti-de Sitter (AdS) spacetime. The limit of high degree polynomials corresponds in this situation to effective interactions involving extreme short-wavelength modes, whose dynamics is crucial for the turbulent instabilities that determine the ultimate fate of small AdS perturbations. We explicitly apply the relevant asymptotic techniques to the case of a self-interacting probe scalar field in AdS and extract a detailed form of the leading large degree behavior, including closed form analytic expressions for the numerical coefficients appearing in the asymptotics.

  4. Brain heart infusion broth may not be a required component for the decontamination process for the isolation of Mycobacterium avium subspecies Paratuberculosis from fecal samples using ESP broth cultures.

    PubMed

    Rajeev, Sreekumari; Berghaus, Roy D; Johnson, Jill; Pence, Mel; Byrum, Beverly; Farrell, Troy; Baldwin, Charles

    2007-11-01

    Based on the authors' laboratory experience indicating that increased bacterial contamination in Mycobacterium avium ssp. paratuberculosis (MAP) cultures may be because of the addition of brain heart infusion broth (BHI) during the decontamination process, this study was designed to examine whether BHI is a required component for the isolation of MAP from ESP(R) broth cultures. Twenty-six National Veterinary Services Laboratory (NVSL) proficiency test samples supplied for the year 2005 were used for the comparison. Two paired sets of samples were processed in the experiment. In one set, the hexadecylpyridinium chloride monohydrate (HPC) and antibiotic brew were prepared in half strength BHI and for the other set, HPC and antibiotic brew were prepared in sterile distilled water. Culture of the 26 samples using the BHI/HPC decontamination method identified 13 (50%) positives, whereas culture using the water/HPC decontamination method identified 14 (54%) positives. The proportions of samples with a positive result did not differ significantly between the 2 decontamination methods. Although in most cases it took longer to identify a positive result by the BHI method, the difference between methods with respect to the number of days to a positive culture result was not statistically significant. Retrospective data collected from the Animal Disease Diagnostic Laboratory, Ohio also suggest that inclusion of BHI in the decontamination protocol may not have any effect on MAP recovery or contamination rate. Elimination of BHI from broth cultures may increase the sensitivity of MAP isolation, and reduce the cost of testing.

  5. Intraperitoneal injection of the pancreatic peptide amylin potently reduces behavioral impairment and brain amyloid pathology in murine models of Alzheimer's disease.

    PubMed

    Zhu, H; Wang, X; Wallack, M; Li, H; Carreras, I; Dedeoglu, A; Hur, J-Y; Zheng, H; Li, H; Fine, R; Mwamburi, M; Sun, X; Kowall, N; Stern, R A; Qiu, W Q

    2015-02-01

    Amylin, a pancreatic peptide, and amyloid-beta peptides (Aβ), a major component of Alzheimer's disease (AD) brain, share similar β-sheet secondary structures, but it is not known whether pancreatic amylin affects amyloid pathogenesis in the AD brain. Using AD mouse models, we investigated the effects of amylin and its clinical analog, pramlintide, on AD pathogenesis. Surprisingly, chronic intraperitoneal (i.p.) injection of AD animals with either amylin or pramlintide reduces the amyloid burden as well as lowers the concentrations of Aβ in the brain. These treatments significantly improve their learning and memory assessed by two behavioral tests, Y maze and Morris water maze. Both amylin and pramlintide treatments increase the concentrations of Aβ1-42 in cerebral spinal fluid (CSF). A single i.p. injection of either peptide also induces a surge of Aβ in the serum, the magnitude of which is proportionate to the amount of Aβ in brain tissue. One intracerebroventricular injection of amylin induces a more significant surge in serum Aβ than one i.p. injection of the peptide. In 330 human plasma samples, a positive association between amylin and Aβ1-42 as well as Aβ1-40 is found only in patients with AD or amnestic mild cognitive impairment. As amylin readily crosses the blood-brain barrier, our study demonstrates that peripheral amylin's action on the central nervous system results in translocation of Aβ from the brain into the CSF and blood that could be an explanation for a positive relationship between amylin and Aβ in blood. As naturally occurring amylin may play a role in regulating Aβ in brain, amylin class peptides may provide a new avenue for both treatment and diagnosis of AD.

  6. Left Brain/Right Brain: Research and Learning. Focused Access to Selected Topics (FAST) Bibliography No. 12.

    ERIC Educational Resources Information Center

    Eppele, Ruth

    This 27-item bibliography represents the variety of articles added to the ERIC database from 1983 through 1988 on left-brain/right-brain research, theory, and application as it relates to classroom incorporation. Included are conflicting opinions as to the usefulness of left-brain/right-brain studies and their application in the learning…

  7. Brain-Derived Neurotrophic Factor Gene Val66Met Polymorphism Is a Risk Factor for Attention-Deficit Hyperactivity Disorder in a Turkish Sample

    PubMed Central

    Ozturk, Onder; Basay, Burge Kabukcu; Buber, Ahmet; Basay, Omer; Alacam, Huseyin; Bacanlı, Ali; Yılmaz, Şenay Görücü; Erdal, Mehmet Emin; Ercan, Eyup Sabri

    2016-01-01

    Objective Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that negatively affects different areas of life. We aimed to evaluate the associations between the Val66Met polymorphism of brain-derived neurotrophic factor (BDNF) and ADHD and to assess the effect of the BDNF polymorphism on the neurocognitive profile and clinical symptomatology in ADHD. Methods Two hundred one ADHD cases and 99 typically developing subjects (TD) between the ages of 8 and 15 years were involved in the study. All subjects were evaluated using a complete neuropsychological battery, Child Behavior Checklist, the Teacher's Report Form (TRF) and the DSM-IV Disruptive Behavior Disorders Rating Scale-teacher and parent forms. Results The GG genotype was significantly more frequent in the patients with ADHD than in the TD controls, and the GG genotype was also significantly more frequent in the ADHD-combined (ADHD-C) subtype patients than in the TDs. However, there were no significant associations of the BDNF polymorphism with the ADHD subtypes or neurocognitive profiles of the patients. The teacher-assessed hyperactivity and inattention symptom count and the total score were higher, and the appropriately behaving subtest score of the TRF was lower in the GG genotypes than in the GA and AA (i.e., the A-containing) genotypes. Conclusion We found a positive association between the BDNF gene Val66Met polymorphism and ADHD, and this association was observed specifically in the ADHD-C subtype and not the ADHD-predominantly inattentive subtype. Our findings support that the Val66Met polymorphism of BDNF gene might be involved in the pathogenesis of ADHD. Furthermore Val66Met polymorphism of BDNF gene may be more closely associated with hyperactivity rather than inattention. PMID:27757130

  8. Holography and AdS4 self-gravitating dyons

    NASA Astrophysics Data System (ADS)

    Lugo, A. R.; Moreno, E. F.; Schaposnik, F. A.

    2010-11-01

    We present a self-gravitating dyon solution of the Einstein-Yang-Mills-Higgs equations of motion in asymptotically AdS space. The back reaction of gauge and Higgs fields on the space-time geometry leads to the metric of an asymptotically AdS black hole. Using the gauge/gravity correspondence we analyze relevant properties of the finite temperature quantum field theory defined on the boundary. In particular we identify an order operator, characterize a phase transition of the dual theory on the border and also compute the expectation value of the finite temperature Wilson loop.

  9. AdS box graphs, unitarity and operator product expansions

    NASA Astrophysics Data System (ADS)

    Hoffmann, L.; Mesref, L.; Rühl, W.

    2000-11-01

    We develop a method of singularity analysis for conformal graphs which, in particular, is applicable to the holographic image of AdS supergravity theory. It can be used to determine the critical exponents for any such graph in a given channel. These exponents determine the towers of conformal blocks that are exchanged in this channel. We analyze the scalar AdS box graph and show that it has the same critical exponents as the corresponding CFT box graph. Thus pairs of external fields couple to the same exchanged conformal blocks in both theories. This is looked upon as a general structural argument supporting the Maldacena hypothesis.

  10. Phases of global AdS black holes

    NASA Astrophysics Data System (ADS)

    Basu, Pallab; Krishnan, Chethan; Subramanian, P. N. Bala

    2016-06-01

    We study the phases of gravity coupled to a charged scalar and gauge field in an asymptotically Anti-de Sitter spacetime ( AdS 4) in the grand canonical ensemble. For the conformally coupled scalar, an intricate phase diagram is charted out between the four relevant solutions: global AdS, boson star, Reissner-Nordstrom black hole and the hairy black hole. The nature of the phase diagram undergoes qualitative changes as the charge of the scalar is changed, which we discuss. We also discuss the new features that arise in the extremal limit.

  11. CFH Variants Affect Structural and Functional Brain Changes and Genetic Risk of Alzheimer's Disease.

    PubMed

    Zhang, Deng-Feng; Li, Jin; Wu, Huan; Cui, Yue; Bi, Rui; Zhou, He-Jiang; Wang, Hui-Zhen; Zhang, Chen; Wang, Dong; Kong, Qing-Peng; Li, Tao; Fang, Yiru; Jiang, Tianzi; Yao, Yong-Gang

    2016-03-01

    The immune response is highly active in Alzheimer's disease (AD). Identification of genetic risk contributed by immune genes to AD may provide essential insight for the prognosis, diagnosis, and treatment of this neurodegenerative disease. In this study, we performed a genetic screening for AD-related top immune genes identified in Europeans in a Chinese cohort, followed by a multiple-stage study focusing on Complement Factor H (CFH) gene. Effects of the risk SNPs on AD-related neuroimaging endophenotypes were evaluated through magnetic resonance imaging scan, and the effects on AD cerebrospinal fluid biomarkers (CSF) and CFH expression changes were measured in aged and AD brain tissues and AD cellular models. Our results showed that the AD-associated top immune genes reported in Europeans (CR1, CD33, CLU, and TREML2) have weak effects in Chinese, whereas CFH showed strong effects. In particular, rs1061170 (P(meta)=5.0 × 10(-4)) and rs800292 (P(meta)=1.3 × 10(-5)) showed robust associations with AD, which were confirmed in multiple world-wide sample sets (4317 cases and 16 795 controls). Rs1061170 (P=2.5 × 10(-3)) and rs800292 (P=4.7 × 10(-4)) risk-allele carriers have an increased entorhinal thickness in their young age and a higher atrophy rate as the disease progresses. Rs800292 risk-allele carriers have higher CSF tau and Aβ levels and severe cognitive decline. CFH expression level, which was affected by the risk-alleles, was increased in AD brains and cellular models. These comprehensive analyses suggested that CFH is an important immune factor in AD and affects multiple pathological changes in early life and during disease progress.

  12. CFH Variants Affect Structural and Functional Brain Changes and Genetic Risk of Alzheimer's Disease.

    PubMed

    Zhang, Deng-Feng; Li, Jin; Wu, Huan; Cui, Yue; Bi, Rui; Zhou, He-Jiang; Wang, Hui-Zhen; Zhang, Chen; Wang, Dong; Kong, Qing-Peng; Li, Tao; Fang, Yiru; Jiang, Tianzi; Yao, Yong-Gang

    2016-03-01

    The immune response is highly active in Alzheimer's disease (AD). Identification of genetic risk contributed by immune genes to AD may provide essential insight for the prognosis, diagnosis, and treatment of this neurodegenerative disease. In this study, we performed a genetic screening for AD-related top immune genes identified in Europeans in a Chinese cohort, followed by a multiple-stage study focusing on Complement Factor H (CFH) gene. Effects of the risk SNPs on AD-related neuroimaging endophenotypes were evaluated through magnetic resonance imaging scan, and the effects on AD cerebrospinal fluid biomarkers (CSF) and CFH expression changes were measured in aged and AD brain tissues and AD cellular models. Our results showed that the AD-associated top immune genes reported in Europeans (CR1, CD33, CLU, and TREML2) have weak effects in Chinese, whereas CFH showed strong effects. In particular, rs1061170 (P(meta)=5.0 × 10(-4)) and rs800292 (P(meta)=1.3 × 10(-5)) showed robust associations with AD, which were confirmed in multiple world-wide sample sets (4317 cases and 16 795 controls). Rs1061170 (P=2.5 × 10(-3)) and rs800292 (P=4.7 × 10(-4)) risk-allele carriers have an increased entorhinal thickness in their young age and a higher atrophy rate as the disease progresses. Rs800292 risk-allele carriers have higher CSF tau and Aβ levels and severe cognitive decline. CFH expression level, which was affected by the risk-alleles, was increased in AD brains and cellular models. These comprehensive analyses suggested that CFH is an important immune factor in AD and affects multiple pathological changes in early life and during disease progress. PMID:26243271

  13. Frozen yogurt with added inulin and isomalt.

    PubMed

    Isik, U; Boyacioglu, D; Capanoglu, E; Erdil, D Nilufer

    2011-04-01

    The objective of this study was to produce a frozen yogurt containing low fat and no added sugar. Samples containing 5% polydextrose, 0.065% aspartame and acesulfame-K mixture, and different levels of inulin and isomalt (5.0, 6.5, and 8.0%) were produced at pilot scale and analyzed for their physical and chemical properties including proximate composition, viscosity, acidity, overrun, melting rate, heat shock stability, as well as sensory characteristics, and viability of lactic acid bacteria. With the addition of inulin and isomalt, viscosity increased by 19 to 52% compared with that of sample B (reduced-fat control). The average calorie values of samples substituted with sweeteners were about 43% lower than that of original sample. Low-calorie frozen yogurt samples melted about 33 to 48% slower than the reduced-fat control sample at 45 min. Based on quantitative descriptive profile test results, statistically significant differences among products were observed for hardness, iciness, foamy melting, whey separation, and sweetness characteristics. The results of principal component analysis showed that the sensory properties of the sample containing 6.5% inulin and 6.5% isomalt were similar to those of control. Lactic acid bacteria counts of frozen yogurt were found to be between 8.12 and 8.49 log values, 3 mo after the production. The overall results showed that it is possible to produce an attractive frozen yogurt product with the incorporation of inulin and isomalt with no added sugar and reduced fat.

  14. The forecaster's added value

    NASA Astrophysics Data System (ADS)

    Turco, M.; Milelli, M.

    2009-09-01

    skill scores of two competitive forecast. It is important to underline that the conclusions refer to the analysis of the Piemonte operational alert system, so they cannot be directly taken as universally true. But we think that some of the main lessons that can be derived from this study could be useful for the meteorological community. In details, the main conclusions are the following: - despite the overall improvement in global scale and the fact that the resolution of the limited area models has increased considerably over recent years, the QPF produced by the meteorological models involved in this study has not improved enough to allow its direct use, that is, the subjective HQPF continues to offer the best performance; - in the forecast process, the step where humans have the largest added value with respect to mathematical models, is the communication. In fact the human characterisation and communication of the forecast uncertainty to end users cannot be replaced by any computer code; - eventually, although there is no novelty in this study, we would like to show that the correct application of appropriated statistical techniques permits a better definition and quantification of the errors and, mostly important, allows a correct (unbiased) communication between forecasters and decision makers.

  15. D-branes on AdS flux compactifications

    NASA Astrophysics Data System (ADS)

    Koerber, Paul; Martucci, Luca

    2008-01-01

    We study D-branes in Script N = 1 flux compactifications to AdS4. We derive their supersymmetry conditions and express them in terms of background generalized calibrations. Basically because AdS has a boundary, the analysis of stability is more subtle and qualitatively different from the usual case of Minkowski compactifications. For instance, stable D-branes filling AdS4 may wrap trivial internal cycles. Our analysis gives a geometric realization of the four-dimensional field theory approach of Freedman and collaborators. Furthermore, the one-to-one correspondence between the supersymmetry conditions of the background and the existence of generalized calibrations for D-branes is clarified and extended to any supersymmetric flux background that admits a time-like Killing vector and for which all fields are time-independent with respect to the associated time. As explicit examples, we discuss supersymmetric D-branes on IIA nearly Kähler AdS4 flux compactifications.

  16. Dyonic AdS black holes from magnetohydrodynamics

    NASA Astrophysics Data System (ADS)

    Caldarelli, Marco M.; Dias, Óscar J. C.; Klemm, Dietmar

    2009-03-01

    We use the AdS/CFT correspondence to argue that large dyonic black holes in anti-de Sitter spacetime are dual to stationary solutions of the equations of relativistic magnetohydrodynamics on the conformal boundary of AdS. The dyonic Kerr-Newman-AdS4 solution corresponds to a charged diamagnetic fluid not subject to any net Lorentz force, due to orthogonal magnetic and electric fields compensating each other. The conserved charges, stress tensor and R-current of the fluid are shown to be in exact agreement with the corresponding quantities of the black hole. Furthermore, we obtain stationary solutions of the Navier-Stokes equations in four dimensions, which yield predictions for (yet to be constructed) charged rotating black strings in AdS5 carrying nonvanishing momentum along the string. Finally, we consider Scherk-Schwarz reduced AdS gravity on a circle. In this theory, large black holes and black strings are dual to lumps of deconfined plasma of the associated CFT. We analyze the effects that a magnetic field introduces in the Rayleigh-Plateau instability of a plasma tube, which is holographically dual to the Gregory-Laflamme instability of a magnetically charged black string.

  17. AdS Branes from Partial Breaking of Superconformal Symmetries

    SciTech Connect

    Ivanov, E.A.

    2005-10-01

    It is shown how the static-gauge world-volume superfield actions of diverse superbranes on the AdS{sub d+1} superbackgrounds can be systematically derived from nonlinear realizations of the appropriate AdS supersymmetries. The latter are treated as superconformal symmetries of flat Minkowski superspaces of the bosonic dimension d. Examples include the N = 1 AdS{sub 4} supermembrane, which is associated with the 1/2 partial breaking of the OSp(1|4) supersymmetry down to the N = 1, d = 3 Poincare supersymmetry, and the T-duality related L3-brane on AdS{sub 5} and scalar 3-brane on AdS{sub 5} x S{sup 1}, which are associated with two different patterns of 1/2 breaking of the SU(2, 2|1) supersymmetry. Another (closely related) topic is the AdS/CFT equivalence transformation. It maps the world-volume actions of the codimension-one AdS{sub d+1} (super)branes onto the actions of the appropriate Minkowski (super)conformal field theories in the dimension d.

  18. Worldsheet dilatation operator for the AdS superstring

    NASA Astrophysics Data System (ADS)

    Ramírez, Israel; Vallilo, Brenno Carlini

    2016-05-01

    In this work we propose a systematic way to compute the logarithmic divergences of composite operators in the pure spinor description of the AdS 5 × S 5 superstring. The computations of these divergences can be summarized in terms of a dilatation operator acting on the local operators. We check our results with some important composite operators of the formalism.

  19. Entanglement temperature and perturbed AdS3 geometry

    NASA Astrophysics Data System (ADS)

    Levine, G. C.; Caravan, B.

    2016-06-01

    Generalizing the first law of thermodynamics, the increase in entropy density δ S (x ) of a conformal field theory (CFT) is proportional to the increase in energy density, δ E (x ) , of a subsystem divided by a spatially dependent entanglement temperature, TE(x ) , a fixed parameter determined by the geometry of the subsystem, crossing over to thermodynamic temperature at high temperatures. In this paper we derive a generalization of the thermodynamic Clausius relation, showing that deformations of the CFT by marginal operators are associated with spatial temperature variations, δ TE(x ) , and spatial energy correlations play the role of specific heat. Using AdS/CFT duality we develop a relationship between a perturbation in the local entanglement temperature of the CFT and the perturbation of the bulk AdS metric. In two dimensions, we demonstrate a method through which direct diagonalizations of the boundary quantum theory may be used to construct geometric perturbations of AdS3 .

  20. Semiquantitative proteomic analysis of human hippocampal tissues from Alzheimer’s disease and age-matched control brains

    PubMed Central

    2013-01-01

    Background Alzheimer’s disease (AD) is the most common type of dementia affecting people over 65 years of age. The hallmarks of AD are the extracellular deposits known as amyloid β plaques and the intracellular neurofibrillary tangles, both of which are the principal players involved in synaptic loss and neuronal cell death. Tau protein and Aβ fragment 1–42 have been investigated so far in cerebrospinal fluid as a potential AD biomarkers. However, an urgent need to identify novel biomarkers which will capture disease in the early stages and with better specificity remains. High-throughput proteomic and pathway analysis of hippocampal tissue provides a valuable source of disease-related proteins and biomarker candidates, since it represents one of the earliest affected brain regions in AD. Results In this study 2954 proteins were identified (with at least 2 peptides for 1203 proteins) from both control and AD brain tissues. Overall, 204 proteins were exclusively detected in AD and 600 proteins in control samples. Comparing AD and control exclusive proteins with cerebrospinal fluid (CSF) literature-based proteome, 40 out of 204 AD related proteins and 106 out of 600 control related proteins were also present in CSF. As most of these proteins were extracellular/secretory origin, we consider them as a potential source of candidate biomarkers that need to be further studied and verified in CSF samples. Conclusions Our semiquantitative proteomic analysis provides one of the largest human hippocampal proteome databases. The lists of AD and control related proteins represent a panel of proteins potentially involved in AD pathogenesis and could also serve as prospective AD diagnostic biomarkers. PMID:23635041

  1. Effective Ad-Hoc Committees.

    ERIC Educational Resources Information Center

    Young, David G.

    1983-01-01

    Ad-hoc committees may be symbolic, informational, or action committees. A literature survey indicates such committees' structural components include a suprasystem and three subsystems involving linkages, production, and implementation. Other variables include size, personal factors, and timing. All the factors carry implications about ad-hoc…

  2. Lorentzian AdS geometries, wormholes, and holography

    SciTech Connect

    Arias, Raul E.; Silva, Guillermo A.; Botta Cantcheff, Marcelo

    2011-03-15

    We investigate the structure of two-point functions for the quantum field theory dual to an asymptotically Lorentzian Anti de Sitter (AdS) wormhole. The bulk geometry is a solution of five-dimensional second-order Einstein-Gauss-Bonnet gravity and causally connects two asymptotically AdS spacetimes. We revisit the Gubser-Klebanov-Polyakov-Witten prescription for computing two-point correlation functions for dual quantum field theories operators O in Lorentzian signature and we propose to express the bulk fields in terms of the independent boundary values {phi}{sub 0}{sup {+-}} at each of the two asymptotic AdS regions; along the way we exhibit how the ambiguity of normalizable modes in the bulk, related to initial and final states, show up in the computations. The independent boundary values are interpreted as sources for dual operators O{sup {+-}} and we argue that, apart from the possibility of entanglement, there exists a coupling between the degrees of freedom living at each boundary. The AdS{sub 1+1} geometry is also discussed in view of its similar boundary structure. Based on the analysis, we propose a very simple geometric criterion to distinguish coupling from entanglement effects among two sets of degrees of freedom associated with each of the disconnected parts of the boundary.

  3. One-loop diagrams in AdS space

    SciTech Connect

    Hung Lingyan; Shang Yanwen

    2011-01-15

    We study the complex scalar loop corrections to the boundary-boundary gauge two-point function in pure AdS space in Poincare coordinates, in the presence of boundary quadratic perturbations to the scalar. These perturbations correspond to double-trace perturbations in the dual CFT and modify the boundary conditions of the bulk scalars in AdS. We find that, in addition to the usual UV divergences, the one-loop calculation suffers from a divergence originating in the limit as the loop vertices approach the AdS horizon. We show that this type of divergence is independent of the boundary coupling; making use of this we extract the finite relative variation of the imaginary part of the loop via Cutkosky rules as the boundary perturbation varies. Applying our methods to compute the effects of a time-dependent impurity to the conductivities using the replica trick in AdS/CFT, we find that generally an IR-relevant disorder reduces the conductivity and that in the extreme low frequency limit the correction due to the impurities overwhelms the planar CFT result even though it is supposedly 1/N{sup 2} suppressed. We also comment on the more physical scenario of a time-independent impurity.

  4. Imaging the Alzheimer Brain

    PubMed Central

    Ashford, J. Wesson; Salehi, Ahmad; Furst, Ansgar; Bayley, Peter; Frisoni, Giovanni B.; Jack, Clifford R.; Sabri, Osama; Adamson, Maheen M.; Coburn, Kerry L.; Olichney, John; Schuff, Norbert; Spielman, Daniel; Edland, Steven D.; Black, Sandra; Rosen, Allyson; Kennedy, David; Weiner, Michael; Perry, George

    2013-01-01

    This supplement to the Journal of Alzheimer's Disease contains more than half of the chapters from The Handbook of Imaging the Alzheimer Brain, which was first presented at the International Conference on Alzheimer's Disease in Paris, in July, 2011. While the Handbook contains 27 chapters that are modified articles from 2009, 2010, and 2011 issues of the Journal of Alzheimer's Disease, this supplement contains the 31 new chapters of that book and an introductory article drawn from the introductions to each section of the book. The Handbook was designed to provide a multilevel overview of the full field of brain imaging related to Alzheimer's disease (AD). The Handbook, as well as this supplement, contains both reviews of the basic concepts of imaging, the latest developments in imaging, and various discussions and perspectives of the problems of the field and promising directions. The Handbook was designed to be useful for students and clinicians interested in AD as well as scientists studying the brain and pathology related to AD. PMID:21971448

  5. Kolmogorov-Zakharov spectrum in AdS gravitational collapse.

    PubMed

    de Oliveira, H P; Pando Zayas, Leopoldo A; Rodrigues, E L

    2013-08-01

    We study black hole formation during the gravitational collapse of a massless scalar field in asymptotically D-dimensional anti-de Sitter AdS(D) spacetimes for D = 4, 5. We conclude that spherically symmetric gravitational collapse in asymptotically AdS spaces is turbulent and characterized by a Kolmogorov-Zakharov spectrum. Namely, we find that after an initial period of weakly nonlinear evolution, there is a regime where the power spectrum of the Ricci scalar evolves as ω(-s) with the frequency, ω, and s ≈ 1.7 ± 0.1.

  6. Brain Power.

    ERIC Educational Resources Information Center

    Albrecht, Karl

    2002-01-01

    Reviews significant findings of recent brain research, including the concept of five minds: automatic, subconscious, practical, creative, and spiritual. Suggests approaches to training the brain that are related to this hierarchy of thinking. (JOW)

  7. Brain Basics

    MedlinePlus

    ... have been linked to many mental disorders, including autism , obsessive compulsive disorder (OCD) , schizophrenia , and depression . Brain ... studies show that brain growth in children with autism appears to peak early. And as they grow ...

  8. Brain components

    MedlinePlus

    ... 3 major components of the brain are the cerebrum, cerebellum, and brain stem. The cerebrum is divided into left and right hemispheres, each ... gray matter) is the outside portion of the cerebrum and provides us with functions associated with conscious ...

  9. Brain Diseases

    MedlinePlus

    The brain is the control center of the body. It controls thoughts, memory, speech, and movement. It regulates the function of many organs. When the brain is healthy, it works quickly and automatically. However, ...

  10. Brain abscess

    MedlinePlus

    Tunkel AR. Brain abscess. In: Bennett JE, Dolin R, Blaser MJ, eds. Mandell, Douglas, and Bennett's Principles and Practice ... Philadelphia, PA: Elsevier Saunders; 2015:chap 92. Tunkel AR, Scheld WM. Brain abscess. In: Winn HR, ed. ...

  11. Semiclassical Virasoro blocks from AdS3 gravity

    NASA Astrophysics Data System (ADS)

    Hijano, Eliot; Kraus, Per; Perlmutter, Eric; Snively, River

    2015-12-01

    We present a unified framework for the holographic computation of Virasoro conformal blocks at large central charge. In particular, we provide bulk constructions that correctly reproduce all semiclassical Virasoro blocks that are known explicitly from conformal field theory computations. The results revolve around the use of geodesic Witten diagrams, recently introduced in [1], evaluated in locally AdS3 geometries generated by backreaction of heavy operators. We also provide an alternative computation of the heavy-light semiclassical block — in which two external operators become parametrically heavy — as a certain scattering process involving higher spin gauge fields in AdS3; this approach highlights the chiral nature of Virasoro blocks. These techniques may be systematically extended to compute corrections to these blocks and to interpolate amongst the different semiclassical regimes.

  12. AdS6 solutions of type II supergravity

    NASA Astrophysics Data System (ADS)

    Apruzzi, Fabio; Fazzi, Marco; Passias, Achilleas; Rosa, Dario; Tomasiello, Alessandro

    2014-11-01

    Very few AdS6 × M 4 supersymmetric solutions are known: one in massive IIA, and two IIB solutions dual to it. The IIA solution is known to be unique; in this paper, we use the pure spinor approach to give a classification for IIB supergravity. We reduce the problem to two PDEs on a two-dimensional space Σ. M 4 is then a fibration of S 2 over Σ; the metric and fluxes are completely determined in terms of the solution to the PDEs. The results seem likely to accommodate near-horizon limits of ( p, q)-fivebrane webs studied in the literature as a source of CFT5's. We also show that there are no AdS6 solutions in eleven-dimensional supergravity.

  13. Conserved higher-spin charges in AdS4

    NASA Astrophysics Data System (ADS)

    Gelfond, O. A.; Vasiliev, M. A.

    2016-03-01

    Gauge invariant conserved conformal currents built from massless fields of all spins in 4d Minkowski space-time and AdS4 are described in the unfolded dynamics approach. The current cohomology associated with non-zero conserved charges is found. The resulting list of charges is shown to match the space of parameters of the conformal higher-spin symmetry algebra in four dimensions.

  14. On information loss in AdS3/CFT2

    DOE PAGES

    Fitzpatrick, A. Liam; Kaplan, Jared; Li, Daliang; Wang, Junpu

    2016-05-18

    We discuss information loss from black hole physics in AdS3, focusing on two sharp signatures infecting CFT2 correlators at large central charge c: ‘forbidden singularities’ arising from Euclidean-time periodicity due to the effective Hawking temperature, and late-time exponential decay in the Lorentzian region. We study an infinite class of examples where forbidden singularities can be resolved by non-perturbative effects at finite c, and we show that the resolution has certain universal features that also apply in the general case. Analytically continuing to the Lorentzian regime, we find that the non-perturbative effects that resolve forbidden singularities qualitatively change the behavior ofmore » correlators at times t ~SBH, the black hole entropy. This may resolve the exponential decay of correlators at late times in black hole backgrounds. By Borel resumming the 1/c expansion of exact examples, we explicitly identify ‘information-restoring’ effects from heavy states that should correspond to classical solutions in AdS3. Lastly, our results suggest a line of inquiry towards a more precise formulation of the gravitational path integral in AdS3.« less

  15. Brain Aneurysm

    MedlinePlus

    A brain aneurysm is an abnormal bulge or "ballooning" in the wall of an artery in the brain. They are sometimes called berry aneurysms because they ... often the size of a small berry. Most brain aneurysms produce no symptoms until they become large, ...

  16. Metabolic profiling of Alzheimer's disease brains

    NASA Astrophysics Data System (ADS)

    Inoue, Koichi; Tsutsui, Haruhito; Akatsu, Hiroyasu; Hashizume, Yoshio; Matsukawa, Noriyuki; Yamamoto, Takayuki; Toyo'Oka, Toshimasa

    2013-08-01

    Alzheimer's disease (AD) is an irreversible, progressive brain disease and can be definitively diagnosed after death through an examination of senile plaques and neurofibrillary tangles in several brain regions. It is to be expected that changes in the concentration and/or localization of low-molecular-weight molecules are linked to the pathological changes that occur in AD, and determining their identity would provide valuable information regarding AD processes. Here, we propose definitive brain metabolic profiling using ultra-performance liquid chromatography coupled with electrospray time-of-flight mass spectrometry analysis. The acquired data were subjected to principal components analysis to differentiate the frontal and parietal lobes of the AD/Control groups. Significant differences in the levels of spermine and spermidine were identified using S-plot, mass spectra, databases and standards. Based on the investigation of the polyamine metabolite pathway, these data establish that the downstream metabolites of ornithine are increased, potentially implicating ornithine decarboxylase activity in AD pathology.

  17. Immunohistochemical analysis of human brain suggests pathological synergism of Alzheimer's disease and diabetes mellitus.

    PubMed

    Valente, Tony; Gella, Alejandro; Fernàndez-Busquets, Xavier; Unzeta, Mercedes; Durany, Nuria

    2010-01-01

    It has been extensively reported that diabetes mellitus (DM) patients have a higher risk of developing Alzheimer's disease (AD), but a mechanistic connection between both pathologies has not been provided so far. Carbohydrate-derived advanced glycation endproducts (AGEs) have been implicated in the chronic complications of DM and have been reported to play an important role in the pathogenesis of AD. The earliest histopathological manifestation of AD is the apparition of extracellular aggregates of the amyloid beta peptide (Abeta). To investigate possible correlations between AGEs and Abeta aggregates with both pathologies, we have performed an immuhistochemical study in human post-mortem samples of AD, AD with diabetes (ADD), diabetic and nondemented controls. ADD brains showed increased number of Abeta dense plaques and receptor for AGEs (RAGE)-positive and Tau-positive cells, higher AGEs levels and major microglial activation, compared to AD brain. Our results indicate that ADD patients present a significant increase of cell damage through a RAGE-dependent mechanism, suggesting that AGEs may promote the generation of an oxidative stress vicious cycle, which can explain the severe progression of patients with both pathologies.

  18. Brain Basics: Know Your Brain

    MedlinePlus

    ... fact sheet is a basic introduction to the human brain. It may help you understand how the healthy ... largest and most highly developed part of the human brain: it consists primarily of the cerebrum ( 2 ) and ...

  19. ADS/CFT and QCD

    SciTech Connect

    Brodsky, Stanley J.; de Teramond, Guy F.; /Costa Rica U. /SLAC

    2007-02-21

    The AdS/CFT correspondence between string theory in AdS space and conformal .eld theories in physical spacetime leads to an analytic, semi-classical model for strongly-coupled QCD which has scale invariance and dimensional counting at short distances and color confinement at large distances. Although QCD is not conformally invariant, one can nevertheless use the mathematical representation of the conformal group in five-dimensional anti-de Sitter space to construct a first approximation to the theory. The AdS/CFT correspondence also provides insights into the inherently non-perturbative aspects of QCD, such as the orbital and radial spectra of hadrons and the form of hadronic wavefunctions. In particular, we show that there is an exact correspondence between the fifth-dimensional coordinate of AdS space z and a specific impact variable {zeta} which measures the separation of the quark and gluonic constituents within the hadron in ordinary space-time. This connection allows one to compute the analytic form of the frame-independent light-front wavefunctions, the fundamental entities which encode hadron properties and allow the computation of decay constants, form factors, and other exclusive scattering amplitudes. New relativistic lightfront equations in ordinary space-time are found which reproduce the results obtained using the 5-dimensional theory. The effective light-front equations possess remarkable algebraic structures and integrability properties. Since they are complete and orthonormal, the AdS/CFT model wavefunctions can also be used as a basis for the diagonalization of the full light-front QCD Hamiltonian, thus systematically improving the AdS/CFT approximation.

  20. No-carrier-added [1.sup.11 c]putrescine

    DOEpatents

    McPherson, Daniel W.; Fowler, Joanna S.; Wolf, Alfred P.

    1989-01-01

    The invention relates to a new radiolabeled imaging agent, no-carrier-added [1-.sup.11 C]putrescine, and to the use of this very pure material as a radiotracer with positron emission tomography for imaging brain tumors. The invention further relates to the synthesis of no-carrier-added [1-.sup.11 C]putrescine based on the Michael addition of potassium .sup.11 C-labeled cyanide to acrylonitrile followed by reduction of the .sup.11 C-labeled dinitrile. The new method is rapid and efficient and provides radiotracer with a specific activity greater than 1.4 curies per millimol and in a purity greater than 95%.

  1. The Brains Behind the Brain.

    ERIC Educational Resources Information Center

    D'Arcangelo, Marcia

    1998-01-01

    Interviews with five neuroscientists--Martin Diamond, Pat Wolfe, Robert Sylwester, Geoffrey Caine, and Eric Jensen--disclose brain-research findings of practical interest to educators. Topics include brain physiology, environmental enrichment, memorization, windows of learning opportunity, brain learning capacity, attention span, student interest,…

  2. Endotoxin-induced lung alveolar cell injury causes brain cell damage

    PubMed Central

    Rodríguez-González, Raquel; Ramos-Nuez, Ángela; Martín-Barrasa, José Luis; López-Aguilar, Josefina; Baluja, Aurora; Álvarez, Julián; Rocco, Patricia RM; Pelosi, Paolo

    2015-01-01

    Sepsis is the most common cause of acute respiratory distress syndrome, a severe lung inflammatory disorder with an elevated morbidity and mortality. Sepsis and acute respiratory distress syndrome involve the release of inflammatory mediators to the systemic circulation, propagating the cellular and molecular response and affecting distal organs, including the brain. Since it has been reported that sepsis and acute respiratory distress syndrome contribute to brain dysfunction, we investigated the brain-lung crosstalk using a combined experimental in vitro airway epithelial and brain cell injury model. Conditioned medium collected from an in vitro lipopolysaccharide-induced airway epithelial cell injury model using human A549 alveolar cells was subsequently added at increasing concentrations (no conditioned, 2%, 5%, 10%, 15%, 25%, and 50%) to a rat mixed brain cell culture containing both astrocytes and neurons. Samples from culture media and cells from mixed brain cultures were collected before treatment, and at 6 and 24 h for analysis. Conditioned medium at 15% significantly increased apoptosis in brain cell cultures 24 h after treatment, whereas 25% and 50% significantly increased both necrosis and apoptosis. Levels of brain damage markers S100 calcium binding protein B and neuron-specific enolase, interleukin-6, macrophage inflammatory protein-2, as well as matrix metalloproteinase-9 increased significantly after treating brain cells with ≥2% conditioned medium. Our findings demonstrated that human epithelial pulmonary cells stimulated with bacterial lipopolysaccharide release inflammatory mediators that are able to induce a translational clinically relevant and harmful response in brain cells. These results support a brain-lung crosstalk during sepsis and sepsis-induced acute respiratory distress syndrome. PMID:25135986

  3. Euclidean and Noetherian entropies in AdS space

    SciTech Connect

    Dutta, Suvankar; Gopakumar, Rajesh

    2006-08-15

    We examine the Euclidean action approach, as well as that of Wald, to the entropy of black holes in asymptotically AdS spaces. From the point of view of holography these two approaches are somewhat complementary in spirit and it is not obvious why they should give the same answer in the presence of arbitrary higher derivative gravity corrections. For the case of the AdS{sub 5} Schwarzschild black hole, we explicitly study the leading correction to the Bekenstein-Hawking entropy in the presence of a variety of higher derivative corrections studied in the literature, including the Type IIB R{sup 4} term. We find a nontrivial agreement between the two approaches in every case. Finally, we give a general way of understanding the equivalence of these two approaches.

  4. New Features in ADS Labs

    NASA Astrophysics Data System (ADS)

    Accomazzi, Alberto; Kurtz, M. J.; Henneken, E. A.; Grant, C. S.; Thompson, D.; Di Milia, G.; Luker, J.; Murray, S. S.

    2013-01-01

    The NASA Astrophysics Data System (ADS) has been working hard on updating its services and interfaces to better support our community's research needs. ADS Labs is a new interface built on the old tried-and-true ADS Abstract Databases, so all of ADS's content is available through it. In this presentation we highlight the new features that have been developed in ADS Labs over the last year: new recommendations, metrics, a citation tool and enhanced fulltext search. ADS Labs has long been providing article-level recommendations based on keyword similarity, co-readership and co-citation analysis of its corpus. We have now introduced personal recommendations, which provide a list of articles to be considered based on a individual user's readership history. A new metrics interface provides a summary of the basic impact indicators for a list of records. These include the total and normalized number of papers, citations, reads, and downloads. Also included are some of the popular indices such as the h, g and i10 index. The citation helper tool allows one to submit a set of records and obtain a list of top 10 papers which cite and/or are cited by papers in the original list (but which are not in it). The process closely resembles the network approach of establishing "friends of friends" via an analysis of the citation network. The full-text search service now covers more than 2.5 million documents, including all the major astronomy journals, as well as physics journals published by Springer, Elsevier, the American Physical Society, the American Geophysical Union, and all of the arXiv eprints. The full-text search interface interface allows users and librarians to dig deep and find words or phrases in the body of the indexed articles. ADS Labs is available at http://adslabs.org

  5. Most general AdS3 boundary conditions

    NASA Astrophysics Data System (ADS)

    Grumiller, Daniel; Riegler, Max

    2016-10-01

    We consider the most general asymptotically anti-de Sitter boundary conditions in three-dimensional Einstein gravity with negative cosmological constant. The metric contains in total twelve independent functions, six of which are interpreted as chemical potentials (or non-normalizable fluctuations) and the other half as canonical boundary charges (or normalizable fluctuations). Their presence modifies the usual Fefferman-Graham expansion. The asymptotic symmetry algebra consists of two sl{(2)}_k current algebras, the levels of which are given by k = ℓ/(4 G N ), where ℓ is the AdS radius and G N the three-dimensional Newton constant.

  6. Introducing ADS 2.0

    NASA Astrophysics Data System (ADS)

    Accomazzi, Alberto; Kurtz, M. J.; Henneken, E. A.; Grant, C. S.; Thompson, D.; Luker, J.; Chyla, R.; Murray, S. S.

    2014-01-01

    In the spring of 1993, the Smithsonian/NASA Astrophysics Data System (ADS) first launched its bibliographic search system. It was known then as the ADS Abstract Service, a component of the larger Astrophysics Data System effort which had developed an interoperable data system now seen as a precursor of the Virtual Observatory. As a result of the massive technological and sociological changes in the field of scholarly communication, the ADS is now completing the most ambitious technological upgrade in its twenty-year history. Code-named ADS 2.0, the new system features: an IT platform built on web and digital library standards; a new, extensible, industrial strength search engine; a public API with various access control capabilities; a set of applications supporting search, export, visualization, analysis; a collaborative, open source development model; and enhanced indexing of content which includes the full-text of astronomy and physics publications. The changes in the ADS platform affect all aspects of the system and its operations, including: the process through which data and metadata are harvested, curated and indexed; the interface and paradigm used for searching the database; and the follow-up analysis capabilities available to the users. This poster describes the choices behind the technical overhaul of the system, the technology stack used, and the opportunities which the upgrade is providing us with, namely gains in productivity and enhancements in our system capabilities.

  7. Nerve growth factor in Alzheimer's disease: increased levels throughout the brain coupled with declines in nucleus basalis.

    PubMed

    Scott, S A; Mufson, E J; Weingartner, J A; Skau, K A; Crutcher, K A

    1995-09-01

    The current study analyzed NGF protein levels in the brains of patients with Alzheimer's disease (AD) as compared with aged neurologically normal individuals. An established two-site ELISA was used to measure NGF-like immunoreactivity in the hippocampus, superior temporal gyrus, superior frontal gyrus, inferior parietal lobule, frontal and occipital cortical poles, cerebellum, amygdala, putamen, and nucleus basalis of Meynert (nbM). ChAT activity was assayed in adjacent tissue samples. NGF levels were also evaluated in Parkinson's disease for comparison with both AD and age-matched control cases. Regardless of the brain bank (University of Cincinnati, Rush Presbyterian St. Luke's Medical Center in Chicago, or University of Alabama at Birmingham), NGF-like activity was at least moderately increased with AD in virtually every brain region examined except for the nbM, in which significant declines were observed. NGF levels were also increased when compared with age-matched Parkinson's cases (frontal cortex). NGF-like activity was not related to age at onset or disease duration in AD cases, nor did NGF levels correlate with age at death in the control or AD groups. Correlations between ChAT and NGF-like activity across brains varied considerably and were generally not significant. The present findings indicate that AD is characterized by a widespread increase in cortical and subcortical NGF. Although a correlation with ChAT activity was not observed in cortex, the AD-related decline in NGF found in nbM is consistent with the possibility of impaired retrograde transport of NGF to this region.

  8. Brain tumors.

    PubMed Central

    Black, K. L.; Mazziotta, J. C.; Becker, D. P.

    1991-01-01

    Recent advances in experimental tumor biology are being applied to critical clinical problems of primary brain tumors. The expression of peripheral benzodiazepine receptors, which are sparse in normal brain, is increased as much as 20-fold in brain tumors. Experimental studies show promise in using labeled ligands to these receptors to identify the outer margins of malignant brain tumors. Whereas positron emission tomography has improved the dynamic understanding of tumors, the labeled selective tumor receptors with positron emitters will enhance the ability to specifically diagnose and greatly aid in the pretreatment planning for tumors. Modulation of these receptors will also affect tumor growth and metabolism. Novel methods to deliver antitumor agents to the brain and new approaches using biologic response modifiers also hold promise to further improve the management of brain tumors. Images PMID:1848735

  9. Conserved charges in timelike warped AdS3 spaces

    NASA Astrophysics Data System (ADS)

    Donnay, L.; Fernández-Melgarejo, J. J.; Giribet, G.; Goya, A.; Lavia, E.

    2015-06-01

    We consider the timelike version of warped anti-de Sitter space (WAdS), which corresponds to the three-dimensional section of the Gödel solution of four-dimensional cosmological Einstein equations. This geometry presents closed timelike curves (CTCs), which are inherited from its four-dimensional embedding. In three dimensions, this type of solution can be supported without matter provided the graviton acquires mass. Here, among the different ways to consistently give mass to the graviton in three dimensions, we consider the parity-even model known as new massive gravity (NMG). In the bulk of timelike WAdS3 space, we introduce defects that, from the three-dimensional point of view, represent spinning massive particlelike objects. For this type of source, we investigate the definition of quasilocal gravitational energy as seen from infinity, far beyond the region where the CTCs appear. We also consider the covariant formalism applied to NMG to compute the mass and the angular momentum of spinning particlelike defects and compare the result with the one obtained by means of the quasilocal stress tensor. We apply these methods to special limits in which the WAdS3 solutions coincide with locally AdS3 and locally AdS2×R spaces. Finally, we make some comments about the asymptotic symmetry algebra of asymptotically WAdS3 spaces in NMG.

  10. Sex-specific association of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and plasma BDNF with attention-deficit/hyperactivity disorder in a drug-naïve Han Chinese sample.

    PubMed

    Li, Haimei; Liu, Lu; Tang, Yilang; Ji, Ning; Yang, Li; Qian, Qiujin; Wang, Yufeng

    2014-07-30

    A functional polymorphism of the brain derived neurotrophic factor gene (BDNF) (Val66Met) has been suggested to be involved in the pathogenesis of attention-deficit/hyperactivity disorder (ADHD). It also has an impact on peripheral BDNF levels in psychiatric disorders. This study examined the association of Val66Met with plasma BDNF level of ADHD in Han Chinese children (170 medication - naïve ADHD patients and 155 unaffected controls, aged 6-16 years). The Val allele was showed a higher frequency in females with ADHD (n=84) than controls (P=0.029) from the case-control association study. The analysis of covariance (ANCOVA) indicated that the mean plasma BDNF levels of ADHD patients were significantly higher than that of controls (P=0.001). We performed both total sample and sex stratified analyses to investigate the effect of Val66Met genotype on the plasma BDNF levels, but only a trend of association was found in females with ADHD (n=84), with a tendency of lower plasma BDNF level in Val allele carriers than Met/Met genotype carriers (P=0.071). Our results suggested a sex-specific association between BDNF and ADHD. Furthermore, there was a possible sex-specific relationship between the BDNF Val66Met genotype and plasma BDNF levels. However, further studies are required to elucidate the role of BDNF in ADHD.

  11. Influence of coagulation factor x on in vitro and in vivo gene delivery by adenovirus (Ad) 5, Ad35, and chimeric Ad5/Ad35 vectors.

    PubMed

    Greig, Jenny A; Buckley, Suzanne Mk; Waddington, Simon N; Parker, Alan L; Bhella, David; Pink, Rebecca; Rahim, Ahad A; Morita, Takashi; Nicklin, Stuart A; McVey, John H; Baker, Andrew H

    2009-10-01

    The binding of coagulation factor X (FX) to the hexon of adenovirus (Ad) 5 is pivotal for hepatocyte transduction. However, vectors based on Ad35, a subspecies B Ad, are in development for cancer gene therapy, as Ad35 utilizes CD46 (which is upregulated in many cancers) for transduction. We investigated whether interaction of Ad35 with FX influenced vector tropism using Ad5, Ad35, and Ad5/Ad35 chimeras: Ad5/fiber(f)35, Ad5/penton(p)35/f35, and Ad35/f5. Surface plasmon resonance (SPR) revealed that Ad35 and Ad35/f5 bound FX with approximately tenfold lower affinities than Ad5 hexon-containing viruses, and electron cryomicroscopy (cryo-EM) demonstrated a direct Ad35 hexon:FX interaction. The presence of physiological levels of FX significantly inhibited transduction of vectors containing Ad35 fibers (Ad5/f35, Ad5/p35/f35, and Ad35) in CD46-positive cells. Vectors were intravenously administered to CD46 transgenic mice in the presence and absence of FX-binding protein (X-bp), resulting in reduced liver accumulation for all vectors. Moreover, Ad5/f35 and Ad5/p35/f35 efficiently accumulated in the lung, whereas Ad5 demonstrated poor lung targeting. Additionally, X-bp significantly reduced lung genome accumulation for Ad5/f35 and Ad5/p35/f35, whereas Ad35 was significantly enhanced. In summary, vectors based on the full Ad35 serotype will be useful vectors for selective gene transfer via CD46 due to a weaker FX interaction compared to Ad5.

  12. Oxidatively modified proteins in Alzheimer’s disease (AD), mild cognitive impairment and animal models of AD: role of Abeta in pathogenesis

    PubMed Central

    Sultana, Rukhsana; Perluigi, Marzia

    2009-01-01

    Oxidative stress has been implicated in the pathogenesis of a number of diseases including Alzheimer’s disease (AD). The oxidative stress hypothesis of AD pathogenesis, in part, is based on β-amyloid peptide (Aβ)-induced oxidative stress in both in vitro and in vivo studies. Oxidative modification of the protein may induce structural changes in a protein that might lead to its functional impairment. A number of oxidatively modified brain proteins were identified using redox proteomics in AD, mild cognitive impairment (MCI) and Aβ models of AD, which support a role of Aβ in the alteration of a number of biochemical and cellular processes such as energy metabolism, protein degradation, synaptic function, neuritic growth, neurotransmission, cellular defense system, long term potentiation involved in formation of memory, etc. All the redox proteomics-identified brain proteins fit well with the appearance of the three histopathological hallmarks of AD, i.e., synapse loss, amyloid plaque formation and neurofibrillary tangle formation and suggest a direct or indirect association of the identified proteins with the pathological and/or biochemical alterations in AD. Further, Aβ models of AD strongly support the notion that oxidative stress induced by Aβ may be a driving force in AD pathogenesis. Studies conducted on arguably the earliest stage of AD, MCI, may elucidate the mechanism(s) leading to AD pathogenesis by identifying early markers of the disease, and to develop therapeutic strategies to slow or prevent the progression of AD. In this review, we summarized our findings of redox proteomics identified oxidatively modified proteins in AD, MCI and AD models. PMID:19288120

  13. Label-Free Quantitative LC–MS Proteomics of Alzheimer’s Disease and Normally Aged Human Brains

    SciTech Connect

    Andreev, Victor P.; Petyuk, Vladislav A.; Brewer, Heather M.; Karpievitch, Yuliya V.; Xie, Fang; Clarke, Jennifer; Camp, David; Smith, Richard D.; Lieberman, Andrew P.; Albin, Roger L.; Nawaz, Zafar; El Hokayem, Jimmy; Myers, Amanda J.

    2012-06-01

    Quantitative proteomics analysis of cortical samples of 10 Alzheimer’s disease (AD) brains versus 10 normally aged brains was performed by following the accurate mass and time tag (AMT) approach with the high resolution LTQ Orbitrap mass spectrometer. More than 1400 proteins were identified and quantitated. A conservative approach of selecting only the consensus results of four normalization methods was suggested and used. A total of 197 proteins were shown to be significantly differentially abundant (p-values <0.05, corrected for multiplicity of testing) in AD versus control brain samples. Thirty-seven of these proteins were reported as differentially abundant or modified in AD in previous proteomics and transcriptomics publications. The rest to the best of our knowledge are new. Mapping of the discovered proteins with bioinformatic tools revealed significant enrichment with differentially abundant proteins of pathways and processes known to be important in AD, including signal transduction, regulation of protein phosphorylation, immune response, cytoskeleton organization, lipid metabolism, energy production, and cell death.

  14. Immunohistoblot analysis on whole human hemispheres from normal and Alzheimer diseased brains.

    PubMed

    Beliczai, Zsuzsa; Varszegi, Szilvia; Gulyas, Balazs; Halldin, Christer; Kasa, Peter; Gulya, Karoly

    2008-12-01

    We demonstrate the feasibility and usefulness of the histoblot immunostaining of cryosections of whole hemispheres of healthy and Alzheimer diseased (AD) human brains by localizing a neuron-specific marker, the anti-neuronal nuclei (NeuN) antigen. As expected, cortical NeuN-immunopositive regions were generally thinner and lighter in the AD brains than in the controls. The advantages of using whole hemisphere histoblots: (1) they provide a low-resolution overview/outline of the antigen distribution in a large surface area, (2) large, thick, and/or unfixed tissue sections from post-mortem samples (perhaps of inferior tissue quality) can be compared, and (3) subsequent immunohistochemistry can be performed on the tissue sections used for the histoblots. PMID:18832000

  15. Added Value in Electronic Publications.

    ERIC Educational Resources Information Center

    Bothma, Theo J. D.

    Electronic publications are flooding the market. Some of these publications are created specifically for the electronic environment, but many are conversions of existing material to electronic format. It is not worth the time and effort merely to publish existing material in electronic format if no value is added in the conversion process. The…

  16. Effects of APOE promoter polymorphism on the topological organization of brain structural connectome in nondemented elderly.

    PubMed

    Shu, Ni; Li, Xin; Ma, Chao; Zhang, Junying; Chen, Kewei; Liang, Ying; Chen, Yaojing; Zhang, Zhanjun

    2015-12-01

    The polymorphism of the Apolipoprotein E (APOE) promoter rs405509 can regulate the transcriptional activity of the APOE gene and is related to Alzheimer's disease (AD). However, its effects on cognitive performance and the underlying brain mechanisms remain unknown. Here, we performed a battery of neuropsychological tests in a large sample (837 subjects) of nondemented elderly Chinese people, and explored the related brain mechanisms via the construction of diffusion MRI-based structural connectome and graph analysis from a subset (84 subjects) of the sample. Cognitively, the rs405509 risk allele (TT) carriers showed decreased attention and execution functions compared with noncarriers (GG/GT). Regarding the topological alterations of the brain connectome, the risk allele group exhibited reduced global and local efficiency of white matter structural networks, mainly in the left anterior and posterior cingulate cortices (PCC). Importantly, the efficiency of the left PCC is correlated with the impaired attention function and mediates the impacts of the rs405509 genotype on attention. These results demonstrated that the rs405509 polymorphism affects attention function in nondemented elderly people, possibly by modulating brain structural connectivity of the PCC. This polymorphism may help us to understand the neural mechanisms of cognitive aging and to serve as a potential marker assessing the risk of AD.

  17. Optimizing power to track brain degeneration in Alzheimer’s disease and mild cognitive impairment with tensor-based morphometry: An ADNI study of 515 subjects

    PubMed Central

    Hua, Xue; Lee, Suh; Yanovsky, Igor; Leow, Alex D.; Chou, Yi-Yu; Ho, April J.; Gutman, Boris; Toga, Arthur W.; Jack, Clifford R.; Bernstein, Matt A.; Reiman, Eric M.; Harvey, Danielle J.; Kornak, John; Schuff, Norbert; Alexander, Gene E.; Weiner, Michael W.; Thompson, Paul M.

    2010-01-01

    Tensor-based morphometry (TBM) is a powerful method to map the 3D profile of brain degeneration in Alzheimer’s disease (AD) and mild cognitive impairment (MCI). We optimized a TBM-based image analysis method to determine what methodological factors, and which image-derived measures, maximize statistical power to track brain change. 3D maps, tracking rates of structural atrophy over time, were created from 1030 longitudinal brain MRI scans (1-year follow-up) of 104 AD patients (age: 75.7 ± 7.2 years; MMSE: 23.3 ± 1.8, at baseline), 254 amnestic MCI subjects (75.0 ± 7.2 years; 27.0 ± 1.8), and 157 healthy elderly subjects (75.9 ± 5.1 years; 29.1 ± 1.0), as part of the Alzheimer’s Disease Neuroimaging Initiative (ADNI). To determine which TBM designs gave greatest statistical power, we compared different linear and nonlinear registration parameters (including different regularization functions), and different numerical summary measures derived from the maps. Detection power was greatly enhanced by summarizing changes in a statistically-defined region-of-interest (ROI) derived from an independent training sample of 22 AD patients. Effect sizes were compared using cumulative distribution function (CDF) plots and false discovery rate methods. In power analyses, the best method required only 48 AD and 88 MCI subjects to give 80% power to detect a 25% reduction in the mean annual change using a two-sided test (at α = 0.05). This is a drastic sample size reduction relative to using clinical scores as outcome measures (619 AD/6797 MCI for the ADAS-Cog, and 408 AD/796 MCI for the Clinical Dementia Rating sum-of-boxes scores). TBM offers high statistical power to track brain changes in large, multi-site neuroimaging studies and clinical trials of AD. PMID:19615450

  18. Thermodynamics of charged Lovelock: AdS black holes

    NASA Astrophysics Data System (ADS)

    Prasobh, C. B.; Suresh, Jishnu; Kuriakose, V. C.

    2016-04-01

    We investigate the thermodynamic behavior of maximally symmetric charged, asymptotically AdS black hole solutions of Lovelock gravity. We explore the thermodynamic stability of such solutions by the ordinary method of calculating the specific heat of the black holes and investigating its divergences which signal second-order phase transitions between black hole states. We then utilize the methods of thermodynamic geometry of black hole spacetimes in order to explain the origin of these points of divergence. We calculate the curvature scalar corresponding to a Legendre-invariant thermodynamic metric of these spacetimes and find that the divergences in the black hole specific heat correspond to singularities in the thermodynamic phase space. We also calculate the area spectrum for large black holes in the model by applying the Bohr-Sommerfeld quantization to the adiabatic invariant calculated for the spacetime.

  19. An investigation of AdS2 backreaction and holography

    NASA Astrophysics Data System (ADS)

    Engelsöy, Julius; Mertens, Thomas G.; Verlinde, Herman

    2016-07-01

    We investigate a dilaton gravity model in AdS2 proposed by Almheiri and Polchinski [1] and develop a 1d effective description in terms of a dynamical boundary time with a Schwarzian derivative action. We show that the effective model is equivalent to a 1d version of Liouville theory, and investigate its dynamics and symmetries via a standard canonical framework. We include the coupling to arbitrary conformal matter and analyze the effective action in the presence of possible sources. We compute commutators of local operators at large time separation, and match the result with the time shift due to a gravitational shockwave interaction. We study a black hole evaporation process and comment on the role of entropy in this model.

  20. Superconformal algebras on the boundary of AdS3

    NASA Astrophysics Data System (ADS)

    Rasmussen, Jørgen

    1999-07-01

    Motivated by recent progress on the correspondence between string theory on nti-de Sitter space and conformal field theory, we provide an explicit construction of an infinite dimensional class of superconformal algebras on the boundary of AdS3. These space-time algebras are N extended superconformal algebras of the kind obtainable by hamiltonian reduction of affine SL(2|N/2) current superalgebras for N even, and are induced by the same current superalgebras residing on the world sheet. Thus, such an extended superconformal algebra is generated by N supercurrents and an SL(N/2) current algebra in addition to a U(1) current algebra. The results are obtained within the framework of free field realizations.

  1. Systematics of Coupling Flows in AdS Backgrounds

    SciTech Connect

    Goldberger, Walter D.; Rothstein, Ira Z.

    2003-03-18

    We give an effective field theory derivation, based on the running of Planck brane gauge correlators, of the large logarithms that arise in the predictions for low energy gauge couplings in compactified AdS}_5 backgrounds, including the one-loop effects of bulk scalars, fermions, and gauge bosons. In contrast to the case of charged scalars coupled to Abelian gauge fields that has been considered previously in the literature, the one-loop corrections are not dominated by a single 4D Kaluza-Klein mode. Nevertheless, in the case of gauge field loops, the amplitudes can be reorganized into a leading logarithmic contribution that is identical to the running in 4D non-Abelian gauge theory, and a term which is not logarithmically enhanced and is analogous to a two-loop effect in 4D. In a warped GUT model broken by the Higgs mechanism in the bulk,we show that the matching scale that appears in the large logarithms induced by the non-Abelian gauge fields is m_{XY}^2/k where m_{XY} is the bulk mass of the XY bosons and k is the AdS curvature. This is in contrast to the UV scale in the logarithmic contributions of scalars, which is simply the bulk mass m. Our results are summarized in a set of simple rules that can be applied to compute the leading logarithmic predictions for coupling constant relations within a given warped GUT model. We present results for both bulk Higgs and boundary breaking of the GUT gauge

  2. Holography beyond conformal invariance and AdS isometry?

    SciTech Connect

    Barvinsky, A. O.

    2015-03-15

    We suggest that the principle of holographic duality be extended beyond conformal invariance and AdS isometry. Such an extension is based on a special relation between functional determinants of the operators acting in the bulk and on its boundary, provided that the boundary operator represents the inverse propagators of the theory induced on the boundary by the Dirichlet boundary value problem in the bulk spacetime. This relation holds for operators of a general spin-tensor structure on generic manifolds with boundaries irrespective of their background geometry and conformal invariance, and it apparently underlies numerous O(N{sup 0}) tests of the AdS/CFT correspondence, based on direct calculation of the bulk and boundary partition functions, Casimir energies, and conformal anomalies. The generalized holographic duality is discussed within the concept of the “double-trace” deformation of the boundary theory, which is responsible in the case of large-N CFT coupled to the tower of higher-spin gauge fields for the renormalization group flow between infrared and ultraviolet fixed points. Potential extension of this method beyond the one-loop order is also briefly discussed.

  3. [Brain metastases].

    PubMed

    Brennum, Jannick; Kosteljanetz, Michael; Roed, Henrik Michael H

    2002-07-01

    The incidence of symptomatic brain metastases in Denmark is about 3500. In the present review, the aetiology, symptomatology, and diagnostic procedures are described. The main topic is a review of current treatments and the evidence for their efficacy. Treatment of brain metastases rarely cures the patient, the goal is rather to improve the quality of life and prolong survival. Without treatment, the median survival following diagnosis of brain metastases is about one month, with steroid treatment two months, with whole brain irradiation four to six months, and after surgery or stereotactic radiosurgery 10-12 months. A relatively simple treatment scheme based on the number of brain metastases and the overall condition of the patient is provided.

  4. Brain peroxisomes.

    PubMed

    Trompier, D; Vejux, A; Zarrouk, A; Gondcaille, C; Geillon, F; Nury, T; Savary, S; Lizard, G

    2014-03-01

    Peroxisomes are essential organelles in higher eukaryotes as they play a major role in numerous metabolic pathways and redox homeostasis. Some peroxisomal abnormalities, which are often not compatible with life or normal development, were identified in severe demyelinating and neurodegenerative brain diseases. The metabolic roles of peroxisomes, especially in the brain, are described and human brain peroxisomal disorders resulting from a peroxisome biogenesis or a single peroxisomal enzyme defect are listed. The brain abnormalities encountered in these disorders (demyelination, oxidative stress, inflammation, cell death, neuronal migration, differentiation) are described and their pathogenesis are discussed. Finally, the contribution of peroxisomal dysfunctions to the alterations of brain functions during aging and to the development of Alzheimer's disease is considered.

  5. ADS's Dexter Data Extraction Applet

    NASA Astrophysics Data System (ADS)

    Demleitner, M.; Accomazzi, A.; Eichhorn, G.; Grant, C. S.; Kurtz, M. J.; Murray, S. S.

    The NASA Astrophysics Data System (ADS) now holds 1.3 million scanned pages, containing numerous plots and figures for which the original data sets are lost or inaccessible. The availability of scans of the figures can significantly ease the regeneration of the data sets. For this purpose, the ADS has developed Dexter, a Java applet that supports the user in this process. Dexter's basic functionality is to let the user manually digitize a plot by marking points and defining the coordinate transformation from the logical to the physical coordinate system. Advanced features include automatic identification of axes, tracing lines and finding points matching a template. This contribution both describes the operation of Dexter from a user's point of view and discusses some of the architectural issues we faced during implementation.

  6. Insulin-resistant brain state: the culprit in sporadic Alzheimer's disease?

    PubMed

    Correia, Sónia C; Santos, Renato X; Perry, George; Zhu, Xiongwei; Moreira, Paula I; Smith, Mark A

    2011-04-01

    Severe abnormalities in brain glucose/energy metabolism and insulin signaling have been documented to take a pivotal role in early sporadic Alzheimer's disease (sAD) pathology. Indeed, the "insulin-resistant brain state" has been hypothesized to form the core of the neurodegenerative events that occur in sAD. In this vein, intracerebroventricular administration of subdiabetogenic doses of streptozotocin (STZ) in rats can induce an insulin-resistant brain state, which is proposed as a suitable experimental model of sAD. This review highlights the involvement of disturbed brain insulin metabolism in sAD etiopathogenesis. Furthermore, current knowledge demonstrates that central STZ administration produces brain pathology and behavioral changes that resemble changes found in sAD patients. The STZ-intracerebroventricularly treated rat represents a promising experimental tool in this field by providing new insights concerning early brain alterations in sAD, which can be translated in novel etiopathogenic and therapeutic approaches in this disease.

  7. Scattering States in AdS/CFT

    SciTech Connect

    Fitzpatrick, A.Liam; Kaplan, Jared; /SLAC

    2012-02-14

    We show that suitably regulated multi-trace primary states in large N CFTs behave like 'in' and 'out' scattering states in the flat-space limit of AdS. Their transition matrix elements approach the exact scattering amplitudes for the bulk theory, providing a natural CFT definition of the flat space S-Matrix. We study corrections resulting from the AdS curvature and particle propagation far from the center of AdS, and show that AdS simply provides an IR regulator that disappears in the flat space limit.

  8. Lack of association between interleukin-1 alpha rs1800587 polymorphism and Alzheimer's disease in two Independent European samples.

    PubMed

    Serretti, Alessandro; Olgiati, Paolo; Politis, Antonis; Malitas, Petros; Albani, Diego; Dusi, Sabrina; Polito, Letizia; De Mauro, Stefania; Zisaki, Aikaterini; Piperi, Christina; Liappas, Ioannis; Stamouli, Evangelia; Mailis, Antonis; Atti, Anna Rita; Morri, Monica; Ujkaj, Manjola; Batelli, Sara; Forloni, Gianluigi; Soldatos, Costantine R; Papadimitriou, George N; De Ronchi, Diana; Kalofoutis, Anastasios

    2009-01-01

    Interleukin-1 (IL1) can contribute to pathophysiology of Alzheimer's disease (AD) by promoting deposition of amyloid-beta in the brain. The gene encoding IL1 alpha (IL1A) has a common polymorphism in its 5' regulatory region (rs1800587) with possible functional effects. IL1A T/T genotype has been associated with AD but the overall effect is modest and negative studies have been published. The aim of this study was to investigate the association of the IL1A rs1800587 polymorphism with AD in two independent case-control groups from Greece (Athens) and Italy (Faenza and Granarolo). Preliminary results from the ongoing sample (110 patients with sporadic AD and 130 nonpsychiatric controls) showed no association between IL1A variants and AD, however C/T heterozygotes had more severe depression in AD (Cornell Scale for Depression in Dementia) compared to other genotypes (F = 4.56, d.f = 1, p = 0.037) after controlling for age, illness duration and cognitive impairment (MMSE). Despite the small sample size and the possibility of a false negative finding, our preliminary data support the hypothesis the IL1A rs1800587 variants are not associated with AD. The effect of the IL1A on depressive symptomatology warrants further investigations, however the lack of a gene-dose relationship would suggest a false positive.

  9. [Brain concussion].

    PubMed

    Pälvimäki, Esa-Pekka; Siironen, Jari; Pohjola, Juha; Hernesniemi, Juha

    2011-01-01

    Brain concussion is a common disturbance caused by external forces or acceleration affecting the head. It may be accompanied by transient loss of consciousness and amnesia. Typical symptoms include headache, nausea and dizziness; these may remain for a week or two. Some patients may experience transient loss of inability to create new memories or other brief impairment of mental functioning. Treatment is symptomatic. Some patients may suffer from prolonged symptoms, the connection of which with brain concession is difficult to show. Almost invariably the prognosis of brain concussion is good.

  10. Histological and direct evidence for the role of complement in the neuroinflammation of AD.

    PubMed

    Veerhuis, Robert

    2011-02-01

    In Alzheimers's disease (AD) a disturbed balance between synthesis and removal of Aβ leads to the formation of Aβ deposits and a reaction of the innate immune system. Little evidence exists for a contribution of the adaptive immune response in AD, as no signs of influx of blood borne cells or presence of immunoglobulins in Aβ deposits are apparent. Factors of the complement(C) system and pentraxins act as pattern recognition molecules and mediate uptake of Aβ by glial cells expressing C-receptors (Crec). These interactions may, however, also lead to synthesis and secretion of reactive oxygen species (ROS), cytokines, chemokines and other potentially neurotoxic agents by the glial cells. Virtually all complement factors are produced in brain, and the expression is increased in AD affected brain areas. In AD brain areas with amyloid deposits especially classical pathway C activation products are readily observed. Also C regulatory proteins (Creg) and Crec can be found in the brain parenchyma and are upregulated, especially under acute inflammatory conditions, such as meningitis. However, under chronic low-grade inflammatory conditions, such as in AD, Creg and to some extent Crec expression may remain at a low level, thereby allowing C activation to proceed, leading to sustained activation of glial cells and neurodegenerative changes. In this review evidence from immunohistochemical, in vitro and animal studies pointing to a role for C activation is discussed, with special focus on the disturbed balance between C activators and Cregs in AD.

  11. Magnetic mass in 4D AdS gravity

    NASA Astrophysics Data System (ADS)

    Araneda, René; Aros, Rodrigo; Miskovic, Olivera; Olea, Rodrigo

    2016-04-01

    We provide a fully covariant expression for the diffeomorphic charge in four-dimensional anti-de Sitter gravity, when the Gauss-Bonnet and Pontryagin terms are added to the action. The couplings of these topological invariants are such that the Weyl tensor and its dual appear in the on-shell variation of the action and such that the action is stationary for asymptotic (anti-)self-dual solutions in the Weyl tensor. In analogy with Euclidean electromagnetism, whenever the self-duality condition is global, both the action and the total charge are identically vanishing. Therefore, for such configurations, the magnetic mass equals the Ashtekhar-Magnon-Das definition.

  12. Canonical energy and hairy AdS black holes

    NASA Astrophysics Data System (ADS)

    Hyun, Seungjoon; Park, Sang-A.; Yi, Sang-Heon

    2016-08-01

    We propose the modified version of the canonical energy which was introduced originally by Hollands and Wald. Our construction depends only on the Euler-Lagrange expression of the system and thus is independent of the ambiguity in the Lagrangian. After some comments on our construction, we briefly mention on the relevance of our construction to the boundary information metric in the context of the AdS/CFT correspondence. We also study the stability of three-dimensional hairy extremal black holes by using our construction.

  13. Brain radiation - discharge

    MedlinePlus

    Radiation - brain - discharge; Cancer-brain radiation; Lymphoma - brain radiation; Leukemia - brain radiation ... Decadron) while you are getting radiation to the brain. It may make you hungrier, cause leg swelling ...

  14. Right Hemisphere Brain Damage

    MedlinePlus

    ... Language and Swallowing / Disorders and Diseases Right Hemisphere Brain Damage [ en Español ] What is right hemisphere brain ... right hemisphere brain damage ? What is right hemisphere brain damage? Right hemisphere brain damage (RHD) is damage ...

  15. Lifshitz-like systems and AdS null deformations

    SciTech Connect

    Narayan, K.

    2011-10-15

    Following K. Balasubramanian and K. Narayan [J. High Energy Phys. 08 (2010) 014], we discuss certain lightlike deformations of AdS{sub 5}xX{sup 5} in type IIB string theory sourced by a lightlike dilaton {Phi}(x{sup +}) dual to the N=4 super Yang-Mills theory with a lightlike varying gauge coupling. We argue that, in the case where the x{sup +} direction is noncompact, these solutions describe anisotropic 3+1-dim Lifshitz-like systems with a potential in the x{sup +} direction generated by the lightlike dilaton. We then describe solutions of this sort with a linear dilaton. This enables a detailed calculation of two-point correlation functions of operators dual to bulk scalars and helps illustrate the spatial structure of these theories. Following this, we discuss a nongeometric string construction involving a compactification along the x{sup +} direction of this linear dilaton system. We also point out similar IIB axionic solutions. Similar bulk arguments for x{sup +}-noncompact can be carried out for deformations of AdS{sub 4}xX{sup 7} in M theory.

  16. AdS black holes from duality in gauged supergravity

    NASA Astrophysics Data System (ADS)

    Halmagyi, Nick; Vanel, Thomas

    2014-04-01

    We study and utilize duality transformations in a particular STU-model of four dimensional gauged supergravity. This model is a truncation of the de Wit-Nicolai =8 theory and as such has a lift to eleven-dimensional supergravity on the seven-sphere. Our duality group is U(1)3 and while it can be applied to any solution of this theory, we consider known asymptotically AdS4, supersymmetric black holes and focus on duality transformations which preserve supersymmetry. For static black holes we generalize the supersymmetric solutions of Cacciatori and Klemm from three magnetic charges to include two additional electric charges and argue that this is co-dimension one in the full space of supersymmetric static black holes in the STU-model. These new static black holes have nontrivial profiles for axions. For rotating black holes, we generalize the known two-parameter supersymmetric solution to include an additional parameter. When lifted to M-theory, these black holes correspond to the near horizon geometry of a stack of BPS rotating M2-branes, spinning on an S 7 which is fibered non-trivially over a Riemann surface.

  17. Stability of charged global AdS4 spacetimes

    NASA Astrophysics Data System (ADS)

    Arias, Raúl; Mas, Javier; Serantes, Alexandre

    2016-09-01

    We study linear and nonlinear stability of asymptotically AdS4 solutions in Einstein-Maxwell-scalar theory. After summarizing the set of static solutions we first examine thermodynamical stability in the grand canonical ensemble and the phase transitions that occur among them. In the second part of the paper we focus on nonlinear stability in the microcanonical ensemble by evolving radial perturbations numerically. We find hints of an instability corner for vanishingly small perturbations of the same kind as the ones present in the uncharged case. Collapses are avoided, instead, if the charge and mass of the perturbations come to close the line of solitons. Finally we examine the soliton solutions. The linear spectrum of normal modes is not resonant and instability turns on at extrema of the mass curve. Linear stability extends to nonlinear stability up to some threshold for the amplitude of the perturbation. Beyond that, the soliton is destroyed and collapses to a hairy black hole. The relative width of this stability band scales down with the charge Q, and does not survive the blow up limit to a planar geometry.

  18. Brain Development

    MedlinePlus

    ... new neural connections every second. This growing brain development is influenced by many factors, including a child’s relationships, experiences and environment. Learn more about the crucial role you play ...

  19. The ADS All Sky Survey

    NASA Astrophysics Data System (ADS)

    Goodman, Alyssa

    We will create the first interactive sky map of astronomers' understanding of the Universe over time. We will accomplish this goal by turning the NASA Astrophysics Data System (ADS), widely known for its unrivaled value as a literature resource, into a data resource. GIS and GPS systems have made it commonplace to see and explore information about goings-on on Earth in the context of maps and timelines. Our proposal shows an example of a program that lets a user explore which countries have been mentioned in the New York Times, on what dates, and in what kinds of articles. By analogy, the goal of our project is to enable this kind of exploration-on the sky-for the full corpus of astrophysical literature available through ADS. Our group's expertise and collaborations uniquely position us to create this interactive sky map of the literature, which we call the "ADS All-Sky Survey." To create this survey, here are the principal steps we need to follow. First, by analogy to "geotagging," we will "astrotag," the ADS literature. Many "astrotags" effectively already exist, thanks to curation efforts at both CDS and NED. These efforts have created links to "source" positions on the sky associated with each of the millions of articles in the ADS. Our collaboration with ADS and CDS will let us automatically extract astrotags for all existing and future ADS holdings. The new ADS Labs, which our group helps to develop, includes the ability for researchers to filter article search results using a variety of "facets" (e.g. sources, keywords, authors, observatories, etc.). Using only extracted astrotags and facets, we can create functionality like what is described in the Times example above: we can offer a map of the density of positions' "mentions" on the sky, filterable by the properties of those mentions. Using this map, researchers will be able to interactively, visually, discover what regions have been studied for what reasons, at what times, and by whom. Second, where

  20. A Novel Matrix-Similarity Based Loss Function for Joint Regression and Classification in AD Diagnosis

    PubMed Central

    Zhu, Xiaofeng; Suk, Heung-Il; Shen, Dinggang

    2014-01-01

    Recent studies on AD/MCI diagnosis have shown that the tasks of identifying brain disease and predicting clinical scores are highly related to each other. Furthermore, it has been shown that feature selection with a manifold learning or a sparse model can handle the problems of high feature dimensionality and small sample size. However, the tasks of clinical score regression and clinical label classification were often conducted separately in the previous studies. Regarding the feature selection, to our best knowledge, most of the previous work considered a loss function defined as an element-wise difference between the target values and the predicted ones. In this paper, we consider the problems of joint regression and classification for AD/MCI diagnosis and propose a novel matrix-similarity based loss function that uses high-level information inherent in the target response matrix and imposes the information to be preserved in the predicted response matrix. The newly devised loss function is combined with a group lasso method for joint feature selection across tasks, i.e., predictions of clinical scores and a class label. In order to validate the effectiveness of the proposed method, we conducted experiments on the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset, and showed that the newly devised loss function helped enhance the performances of both clinical score prediction and disease status identification, outperforming the state-of-the-art methods. PMID:24911377

  1. Brain imaging and brain function

    SciTech Connect

    Sokoloff, L.

    1985-01-01

    This book is a survey of the applications of imaging studies of regional cerebral blood flow and metabolism to the investigation of neurological and psychiatric disorders. Contributors review imaging techniques and strategies for measuring regional cerebral blood flow and metabolism, for mapping functional neural systems, and for imaging normal brain functions. They then examine the applications of brain imaging techniques to the study of such neurological and psychiatric disorders as: cerebral ischemia; convulsive disorders; cerebral tumors; Huntington's disease; Alzheimer's disease; depression and other mood disorders. A state-of-the-art report on magnetic resonance imaging of the brain and central nervous system rounds out the book's coverage.

  2. MRI-based brain atrophy rates in ADNI phase 2: acceleration and enrichment considerations for clinical trials.

    PubMed

    Hua, Xue; Ching, Christopher R K; Mezher, Adam; Gutman, Boris A; Hibar, Derrek P; Bhatt, Priya; Leow, Alex D; Jack, Clifford R; Bernstein, Matt A; Weiner, Michael W; Thompson, Paul M

    2016-01-01

    The goal of this work was to assess statistical power to detect treatment effects in Alzheimer's disease (AD) clinical trials using magnetic resonance imaging (MRI)-derived brain biomarkers. We used unbiased tensor-based morphometry (TBM) to analyze n = 5,738 scans, from Alzheimer's Disease Neuroimaging Initiative 2 participants scanned with both accelerated and nonaccelerated T1-weighted MRI at 3T. The study cohort included 198 healthy controls, 111 participants with significant memory complaint, 182 with early mild cognitive impairment (EMCI) and 177 late mild cognitive impairment (LMCI), and 155 AD patients, scanned at screening and 3, 6, 12, and 24 months. The statistical power to track brain change in TBM-based imaging biomarkers depends on the interscan interval, disease stage, and methods used to extract numerical summaries. To achieve reasonable sample size estimates for potential clinical trials, the minimal scan interval was 6 months for LMCI and AD and 12 months for EMCI. TBM-based imaging biomarkers were not sensitive to MRI scan acceleration, which gave results comparable with nonaccelerated sequences. ApoE status and baseline amyloid-beta positron emission tomography data improved statistical power. Among healthy, EMCI, and LMCI participants, sample size requirements were significantly lower in the amyloid+/ApoE4+ group than for the amyloid-/ApoE4- group. ApoE4 strongly predicted atrophy rates across brain regions most affected by AD, but the remaining 9 of the top 10 AD risk genes offered no added predictive value in this cohort. PMID:26545631

  3. The conflicting role of brain cholesterol in Alzheimer's disease: lessons from the brain plasminogen system.

    PubMed

    Ledesma, Maria Dolores; Dotti, Carlos G

    2005-01-01

    Retrospective clinical studies indicate that individuals chronically treated with cholesterol synthesis inhibitors, statins, are at lower risk of developing AD (Alzheimer's disease). Moreover, treatment of guinea pigs with high doses of simvastatin or drastic reduction of cholesterol in cultured cells decrease Abeta (beta-amyloid peptide) production. These data sustain the concept that high brain cholesterol is responsible for Abeta accumulation in AD, providing the scientific support for the proposed use of statins to prevent this disease. However, a number of unresolved issues raise doubts that high brain cholesterol is to blame. First, it has not been shown that higher neuronal cholesterol increases Abeta production. Secondly, it has not been demonstrated that neurons in AD have more cholesterol than control neurons. On the contrary, the brains of AD patients show a specific down-regulation of seladin-1, a protein involved in cholesterol synthesis, and low membrane cholesterol was observed in hippocampal membranes of ApoE4 (apolipoprotein E4) AD cases. This effect was also evidenced by altered cholesterol-rich membrane domains (rafts) and raft-mediated functions, such as diminished generation of the Abeta-degrading enzyme plasmin. Thirdly, numerous genetic defects that cause neurodegeneration are due to defective cholesterol metabolism. Fourthly, in female mice, the most brain-permeant statin induces neurodegeneration and high amyloid production. Altogether, this evidence makes it difficult to accept that statins are beneficial through acting as brain cholesterol-synthesis inhibitors. It appears more likely that their advantageous role arises from improved brain oxygenation.

  4. Brain inflammation in Alzheimer disease and the therapeutic implications.

    PubMed

    McGeer, E G; McGeer, P L

    1999-10-01

    Immunohistochemical studies suggested the existence of a chronic inflammatory condition in affected regions of the brain in Alzheimer disease (AD). Since inflammation can be damaging to host tissue, it was hypothesized that antiinflammatory drugs might inhibit both the onset and the progression of AD. This hypothesis is supported by a number of epidemiological studies suggesting that the prevalence of AD in persons is reduced by 40 - 50% in persons using antiinflammatory drugs. In one small pilot trial in early AD, the nonsteroidal antiinflammatory drug indomethacin appeared to halt the progressive memory loss. Immunohistochemical and molecular biological studies on immune system components in AD brain are revealing the complexities of the innate immune reaction. This very complexity may offer points of therapeutic intervention for new types of antiinflammatory agents. The complement system, microglia and cytokines are key components. This review summarizes the present state of knowledge on the immune system elements found in AD brain.

  5. Alzheimer disease (AD) specific transcription, DNA methylation and splicing in twenty AD associated loci.

    PubMed

    Humphries, Crystal; Kohli, Martin A; Whitehead, Patrice; Mash, Deborah C; Pericak-Vance, Margaret A; Gilbert, John

    2015-07-01

    Genome-wide association studies have identified twenty loci associated with late-onset Alzheimer disease (LOAD). We examined each of the twenty loci, specifically the ±50kb region surrounding the most strongly associated variant, for changes in gene(s) transcription specific to LOAD. Post-mortem human brain samples were examined for expression, methylation, and splicing differences. LOAD specific differences were detected by comparing LOAD to normal and "disease" controls. Eight loci, prominently ABCA7, contain LOAD specific differences. Significant changes in the CELF1 and ZCWPW1 loci occurred in genes not located nearest the associated variant, suggesting that these genes should be investigated further as LOAD candidates.

  6. Condom ads slated for TV.

    PubMed

    1987-02-20

    3 CBS-owned television stations and NBC's New York television station announced yesterday that they would begin accepting condom advertising. In addition, the ABC network announced it will begin running a 30-second public service message with Dr. C. Everett Koop, the US surgeon general, saying that condoms are the best protection against sexual transmission of AIDS. CBS said it will allow the 4 television stations and 18 radio stations it owns to accept condom advertising based on the attitudes of the local viewing or listening community. WCBS-TV in New York, WCAU-TV in Philadelphia and KCBS-TV in Los Angeles said they would accept such ads. CBS also owns a television station in Chicago. WCAU will air condom ads after 11 p.m. only, beginning probably next week, said Paul Webb, a station spokesman. "We recognize the legitimate sensitivities of some members of the community in regard to this issue," said Steve Cohen, the WCAU general manager. "However, it is the judgment of this station that the importance of providing information about the AIDS epidemic and means of prevention is an overriding consideration." NBC's New York television station, WNBC, announced that it will accept condom advertising and public service announcements. PMID:12269166

  7. Chernobyl Birds Have Smaller Brains

    PubMed Central

    Møller, Anders Pape; Bonisoli-Alquati, Andea; Rudolfsen, Geir; Mousseau, Timothy A.

    2011-01-01

    Background Animals living in areas contaminated by radioactive material from Chernobyl suffer from increased oxidative stress and low levels of antioxidants. Therefore, normal development of the nervous system is jeopardized as reflected by high frequencies of developmental errors, reduced brain size and impaired cognitive abilities in humans. Alternatively, associations between psychological effects and radiation have been attributed to post-traumatic stress in humans. Methodology/Principal Finding Here we used an extensive sample of 550 birds belonging to 48 species to test the prediction that even in the absence of post-traumatic stress, there is a negative association between relative brain size and level of background radiation. We found a negative association between brain size as reflected by external head volume and level of background radiation, independent of structural body size and body mass. The observed reduction in brain size in relation to background radiation amounted to 5% across the range of almost a factor 5,000 in radiation level. Species differed significantly in reduction in brain size with increasing background radiation, and brain size was the only morphological character that showed a negative relationship with radiation. Brain size was significantly smaller in yearlings than in older individuals. Conclusions/Significance Low dose radiation can have significant effects on normal brain development as reflected by brain size and therefore potentially cognitive ability. The fact that brain size was smaller in yearlings than in older individuals implies that there was significant directional selection on brain size with individuals with larger brains experiencing a viability advantage. PMID:21390202

  8. Selective accumulation of aluminum in cerebral arteries in Alzheimer's disease (AD).

    PubMed

    Bhattacharjee, Surjyadipta; Zhao, Yuhai; Hill, James M; Culicchia, Frank; Kruck, Theodore P A; Percy, Maire E; Pogue, Aileen I; Walton, J R; Lukiw, Walter J

    2013-09-01

    Once biologically available aluminum bypasses gastrointestinal and blood-brain barriers, this environmentally-abundant neurotoxin has an exceedingly high affinity for the large pyramidal neurons of the human brain hippocampus. This same anatomical region of the brain is also targeted by the earliest evidence of Alzheimer's disease (AD) neuropathology. The mechanism for the selective targeting and transport of aluminum into the hippocampus of the human brain is not well understood. In an effort to improve our understanding of a pathological aluminum entry system into the brain, this study examined the aluminum content of 8 arteries that supply blood to the hippocampus, including the aorta and several cerebral arteries. In contrast to age-matched controls, in AD patients we found a gradient of increasing aluminum concentration from the aorta to the posterior cerebral artery that supplies blood to the hippocampus. Primary cultures of human brain endothelial cells were found to have an extremely high affinity for aluminum when compared to other types of brain cells. Together, these results suggest for the first time that endothelial cells that line the cerebral vasculature may have biochemical attributes conducive to binding and targeting aluminum to selective anatomical regions of the brain, such as the hippocampus, with potential downstream pro-inflammatory and pathogenic consequences.

  9. Differential Brain Responses to Cries of Infants with Autistic Disorder and Typical Development: An fMRI Study

    ERIC Educational Resources Information Center

    Venuti, Paola; Caria, Andrea; Esposito, Gianluca; De Pisapia, Nicola; Bornstein, Marc H.; de Falco, Simona

    2012-01-01

    This study used fMRI to measure brain activity during adult processing of cries of infants with autistic disorder (AD) compared to cries of typically developing (TD) infants. Using whole brain analysis, we found that cries of infants with AD compared to those of TD infants elicited enhanced activity in brain regions associated with verbal and…

  10. Adding a lens Improves spinning speed characterization.

    PubMed

    Mihaliuk, Eugene; Gullion, Terry

    2015-11-01

    Highly stable sample rotation is important in many solid-state NMR experiments. Whether the necessary stability is achieved is not always clear. Typically only an average frequency over some time interval (often relatively long and unknown) is available from the spinning speed controller readout, which is not representative of the short-term variations of instantaneous rotation frequency. The necessity of the relatively slow measurement of spinning speed is a consequence of phase noise in the tachometer, which prevents speed measurement to be both rapid and precise at the same time. We show that adding a lens to the tachometer, without any other changes in the probe, reduces phase noise by nearly an order of magnitude and allows improved measurement of the spinning speed.

  11. Droplet Number Concentration Value-Added Product

    SciTech Connect

    Riihimaki, L.; McFarlane, S.; Sivaraman, C.

    2014-06-01

    The ndrop_mfrsr value-added product (VAP) provides an estimate of the cloud droplet number concentration of overcast water clouds retrieved from cloud optical depth from the multi-filter rotating shadowband radiometer (MFRSR) instrument and liquid water path (LWP) retrieved from the microwave radiometer (MWR). When cloud layer information is available from vertically pointing lidar and radars in the Active Remote Sensing of Clouds (ARSCL) product, the VAP also provides estimates of the adiabatic LWP and an adiabatic parameter (beta) that indicates how divergent the LWP is from the adiabatic case. quality control (QC) flags (qc_drop_number_conc), an uncertainty estimate (drop_number_conc_toterr), and a cloud layer type flag (cloud_base_type) are useful indicators of the quality and accuracy of any given value of the retrieval. Examples of these major input and output variables are given in sample plots in section 6.0.

  12. Quantitative analysis of diffusion tensor imaging (DTI) using statistical parametric mapping (SPM) for brain disorders

    NASA Astrophysics Data System (ADS)

    Lee, Jae-Seung; Im, In-Chul; Kang, Su-Man; Goo, Eun-Hoe; Kwak, Byung-Joon

    2013-07-01

    This study aimed to quantitatively analyze data from diffusion tensor imaging (DTI) using statistical parametric mapping (SPM) in patients with brain disorders and to assess its potential utility for analyzing brain function. DTI was obtained by performing 3.0-T magnetic resonance imaging for patients with Alzheimer's disease (AD) and vascular dementia (VD), and the data were analyzed using Matlab-based SPM software. The two-sample t-test was used for error analysis of the location of the activated pixels. We compared regions of white matter where the fractional anisotropy (FA) values were low and the apparent diffusion coefficients (ADCs) were increased. In the AD group, the FA values were low in the right superior temporal gyrus, right inferior temporal gyrus, right sub-lobar insula, and right occipital lingual gyrus whereas the ADCs were significantly increased in the right inferior frontal gyrus and right middle frontal gyrus. In the VD group, the FA values were low in the right superior temporal gyrus, right inferior temporal gyrus, right limbic cingulate gyrus, and right sub-lobar caudate tail whereas the ADCs were significantly increased in the left lateral globus pallidus and left medial globus pallidus. In conclusion by using DTI and SPM analysis, we were able to not only determine the structural state of the regions affected by brain disorders but also quantitatively analyze and assess brain function.

  13. There are no differences in IL-6, CRP and homocystein concentrations between women whose mothers had AD and women whose mothers did not have AD.

    PubMed

    Devčić, Sanja; Glamuzina, Ljubomir; Ruljancic, Nedjeljka; Mihanovic, Mate

    2014-12-30

    A wide range of recent studies have detected inflammation as one of the most influent factors in the appearance and spreading of neurodegenerative brain diseases. We aimed to understand the influence of Interleukin-6 (IL-6), C-reactive protein (CRP) and homocysteine (Hcy) on patients suffering from Alzheimer׳s disease (AD) and on their descendants. Three groups of subjects were analyzed: 55 patients suffering from AD, 51 middle-aged daughters of the patients of the first group, and 53 subjects without positive family history of AD. The results of the conducted research are in accordance with the present scientific knowledge, namely a statistically significant difference for examined parameters has been determined between women suffering from AD and their daughters and control group examinees. No difference was found in serum concentrations of IL-6, highly sensitive C-reactive protein (hsCRP) and Hcy between the groups of the middle-aged descendants of patients with AD and healthy controls without family history of AD. This finding supports the hypothesis that these markers may not play causal role in the development of AD. This is supported by the obtained positive correlation between IL-6 and hsCRP and IL-6 and Hcy in AD patients while there is no such correlation between female subjects with or without a family history of AD. PMID:25240941

  14. Regional brain stiffness changes across the Alzheimer's disease spectrum☆

    PubMed Central

    Murphy, Matthew C.; Jones, David T.; Jack, Clifford R.; Glaser, Kevin J.; Senjem, Matthew L.; Manduca, Armando; Felmlee, Joel P.; Carter, Rickey E.; Ehman, Richard L.; Huston, John

    2015-01-01

    Magnetic resonance elastography (MRE) is an MRI-based technique to noninvasively measure tissue stiffness. Currently well established for clinical use in the liver, MRE is increasingly being investigated to measure brain stiffness as a novel biomarker of a variety of neurological diseases. The purpose of this work was to apply a recently developed MRE pipeline to measure regional brain stiffness changes in human subjects across the Alzheimer's disease (AD) spectrum, and to gain insights into the biological processes underlying those stiffness changes by correlating stiffness with existing biomarkers of AD. The results indicate that stiffness changes occur mostly in the frontal, parietal and temporal lobes, in accordance with the known topography of AD pathology. Furthermore, stiffness in those areas correlates with existing imaging biomarkers of AD including hippocampal volumes and amyloid PET. Additional analysis revealed preliminary but significant evidence that the relationship between brain stiffness and AD severity is nonlinear and non-monotonic. Given that similar relationships have been observed in functional MRI experiments, we used task-free fMRI data to test the hypothesis that brain stiffness was sensitive to structural changes associated with altered functional connectivity. The analysis revealed that brain stiffness is significantly and positively correlated with default mode network connectivity. Therefore, brain stiffness as measured by MRE has potential to provide new and essential insights into the temporal dynamics of AD, as well as the relationship between functional and structural plasticity as it relates to AD pathophysiology. PMID:26900568

  15. Regional brain stiffness changes across the Alzheimer's disease spectrum.

    PubMed

    Murphy, Matthew C; Jones, David T; Jack, Clifford R; Glaser, Kevin J; Senjem, Matthew L; Manduca, Armando; Felmlee, Joel P; Carter, Rickey E; Ehman, Richard L; Huston, John

    2016-01-01

    Magnetic resonance elastography (MRE) is an MRI-based technique to noninvasively measure tissue stiffness. Currently well established for clinical use in the liver, MRE is increasingly being investigated to measure brain stiffness as a novel biomarker of a variety of neurological diseases. The purpose of this work was to apply a recently developed MRE pipeline to measure regional brain stiffness changes in human subjects across the Alzheimer's disease (AD) spectrum, and to gain insights into the biological processes underlying those stiffness changes by correlating stiffness with existing biomarkers of AD. The results indicate that stiffness changes occur mostly in the frontal, parietal and temporal lobes, in accordance with the known topography of AD pathology. Furthermore, stiffness in those areas correlates with existing imaging biomarkers of AD including hippocampal volumes and amyloid PET. Additional analysis revealed preliminary but significant evidence that the relationship between brain stiffness and AD severity is nonlinear and non-monotonic. Given that similar relationships have been observed in functional MRI experiments, we used task-free fMRI data to test the hypothesis that brain stiffness was sensitive to structural changes associated with altered functional connectivity. The analysis revealed that brain stiffness is significantly and positively correlated with default mode network connectivity. Therefore, brain stiffness as measured by MRE has potential to provide new and essential insights into the temporal dynamics of AD, as well as the relationship between functional and structural plasticity as it relates to AD pathophysiology.

  16. Autoimmune Manifestations in the 3xTg-AD Model of Alzheimer's Disease

    PubMed Central

    Marchese, Monica; Cowan, David; Head, Elizabeth; Ma, Donglai; Karimi, Khalil; Ashthorpe, Vanessa; Kapadia, Minesh; Zhao, Hui; Davis, Paulina; Sakic, Boris

    2015-01-01

    Background Immune system activation is frequently reported in patients with Alzheimer's disease (AD). However, it remains unknown whether this is a cause, a consequence, or an epiphenomenon of brain degeneration. Objective The present study examines whether immunological abnormalities occur in a well-established murine AD model and if so, how they relate temporally to behavioral deficits and neuropathology. Methods A broad battery of tests was employed to assess behavioral performance and autoimmune/inflammatory markers in 3xTg-AD (AD) mice and wild type controls from 1.5 to 12 months of age. Results Aged AD mice displayed severe manifestations of systemic autoimmune/inflammatory disease, as evidenced by splenomegaly, hepatomegaly, elevated serum levels of anti-nuclear/anti-dsDNA antibodies, low hematocrit, and increased number of double-negative T splenocytes. However, anxiety-related behavior and altered spleen function were evident as early as 2 months of age, thus preceding typical AD-like brain pathology. Moreover, AD mice showed altered olfaction and impaired “cognitive” flexibility in the first 6 months of life, suggesting mild cognitive impairment-like manifestations before general learning/memory impairments emerged at an older age. Interestingly, all of these features were present in 3xTg-AD mice prior to significant amyloid-β or tau pathology. Conclusion The results indicate that behavioral deficits in AD mice develop in parallel with systemic autoimmune/inflammatory disease. These changes antedate AD-like neuropathology, thus supporting a causal link between autoimmunity and aberrant behavior. Consequently, 3xTg-AD mice may be a useful model in elucidating the role of immune system in the etiology of AD. PMID:24150111

  17. A Spectral Graph Regression Model for Learning Brain Connectivity of Alzheimer’s Disease

    PubMed Central

    Hu, Chenhui; Cheng, Lin; Sepulcre, Jorge; Johnson, Keith A.; Fakhri, Georges E.; Lu, Yue M.; Li, Quanzheng

    2015-01-01

    Understanding network features of brain pathology is essential to reveal underpinnings of neurodegenerative diseases. In this paper, we introduce a novel graph regression model (GRM) for learning structural brain connectivity of Alzheimer's disease (AD) measured by amyloid-β deposits. The proposed GRM regards 11C-labeled Pittsburgh Compound-B (PiB) positron emission tomography (PET) imaging data as smooth signals defined on an unknown graph. This graph is then estimated through an optimization framework, which fits the graph to the data with an adjustable level of uniformity of the connection weights. Under the assumed data model, results based on simulated data illustrate that our approach can accurately reconstruct the underlying network, often with better reconstruction than those obtained by both sample correlation and ℓ1-regularized partial correlation estimation. Evaluations performed upon PiB-PET imaging data of 30 AD and 40 elderly normal control (NC) subjects demonstrate that the connectivity patterns revealed by the GRM are easy to interpret and consistent with known pathology. Moreover, the hubs of the reconstructed networks match the cortical hubs given by functional MRI. The discriminative network features including both global connectivity measurements and degree statistics of specific nodes discovered from the AD and NC amyloid-beta networks provide new potential biomarkers for preclinical and clinical AD. PMID:26024224

  18. Physical Activity, Mediterranean Diet and Biomarkers-Assessed Risk of Alzheimer’s: A Multi-Modality Brain Imaging Study

    PubMed Central

    Matthews, Dawn C.; Davies, Michelle; Murray, John; Williams, Schantel; Tsui, Wai H.; Li, Yi; Andrews, Randolph D.; Lukic, Ana; McHugh, Pauline; Vallabhajosula, Shankar; de Leon, Mony J.; Mosconi, Lisa

    2014-01-01

    -burden (p < 0.001), although the LTA × MeDi interaction was significant only for FDG measures (p < 0.03). Adjusting for covariates did not attenuate these relationships. Conclusion Lower physical activity and MeDi adherence were associated with increased brain AD-burden among NL individuals, indicating that lifestyle factors may modulate AD risk. Studies with larger samples and longitudinal evaluations are needed to determine the predictive power of the observed associations PMID:25599008

  19. Autosomal Dominant Alzheimer Disease: A Unique Resource to Study CSF Biomarker Changes in Preclinical AD

    PubMed Central

    Schindler, Suzanne Elizabeth; Fagan, Anne M.

    2015-01-01

    Our understanding of the pathogenesis of Alzheimer disease (AD) has been greatly influenced by investigation of rare families with autosomal dominant mutations that cause early onset AD. Mutations in the genes coding for amyloid precursor protein (APP), presenilin 1 (PSEN-1), and presenilin 2 (PSEN-2) cause over-production of the amyloid-β peptide (Aβ) leading to early deposition of Aβ in the brain, which in turn is hypothesized to initiate a cascade of processes, resulting in neuronal death, cognitive decline, and eventual dementia. Studies of cerebrospinal fluid (CSF) from individuals with the common form of AD, late-onset AD (LOAD), have revealed that low CSF Aβ42 and high CSF tau are associated with AD brain pathology. Herein, we review the literature on CSF biomarkers in autosomal dominant AD (ADAD), which has contributed to a detailed road map of AD pathogenesis, especially during the preclinical period, prior to the appearance of any cognitive symptoms. Current drug trials are also taking advantage of the unique characteristics of ADAD and utilizing CSF biomarkers to accelerate development of effective therapies for AD. PMID:26175713

  20. White matter hyperintensities and imaging patterns of brain ageing in the general population.

    PubMed

    Habes, Mohamad; Erus, Guray; Toledo, Jon B; Zhang, Tianhao; Bryan, Nick; Launer, Lenore J; Rosseel, Yves; Janowitz, Deborah; Doshi, Jimit; Van der Auwera, Sandra; von Sarnowski, Bettina; Hegenscheid, Katrin; Hosten, Norbert; Homuth, Georg; Völzke, Henry; Schminke, Ulf; Hoffmann, Wolfgang; Grabe, Hans J; Davatzikos, Christos

    2016-04-01

    White matter hyperintensities are associated with increased risk of dementia and cognitive decline. The current study investigates the relationship between white matter hyperintensities burden and patterns of brain atrophy associated with brain ageing and Alzheimer's disease in a large populatison-based sample (n = 2367) encompassing a wide age range (20-90 years), from the Study of Health in Pomerania. We quantified white matter hyperintensities using automated segmentation and summarized atrophy patterns using machine learning methods resulting in two indices: the SPARE-BA index (capturing age-related brain atrophy), and the SPARE-AD index (previously developed to capture patterns of atrophy found in patients with Alzheimer's disease). A characteristic pattern of age-related accumulation of white matter hyperintensities in both periventricular and deep white matter areas was found. Individuals with high white matter hyperintensities burden showed significantly (P < 0.0001) lower SPARE-BA and higher SPARE-AD values compared to those with low white matter hyperintensities burden, indicating that the former had more patterns of atrophy in brain regions typically affected by ageing and Alzheimer's disease dementia. To investigate a possibly causal role of white matter hyperintensities, structural equation modelling was used to quantify the effect of Framingham cardiovascular disease risk score and white matter hyperintensities burden on SPARE-BA, revealing a statistically significant (P < 0.0001) causal relationship between them. Structural equation modelling showed that the age effect on SPARE-BA was mediated by white matter hyperintensities and cardiovascular risk score each explaining 10.4% and 21.6% of the variance, respectively. The direct age effect explained 70.2% of the SPARE-BA variance. Only white matter hyperintensities significantly mediated the age effect on SPARE-AD explaining 32.8% of the variance. The direct age effect explained 66.0% of the SPARE-AD

  1. Political Ads vs. News as Sources of Issue Information.

    ERIC Educational Resources Information Center

    Zhao, Xinshu; Chaffee, Steven H.

    A study reexamined survey data collected in late October 1984 in order to test the validity of the generalization that people are influenced more by television ads than they are by television news. Sampling was based on random digit dialing in Dane County, Wisconsin, and 416 interviews conducted by telephone. Data analysis indicated that the…

  2. New value-added materials from ethanol by-products

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Value-added materials were obtained from a distillers dried grains (DDG) sample obtained from MCP Corporation. It was processed by jet cooking at various pH levels and fractionated. Among the various fractions, free flowing particles were obtained that appear to have several opportunities for a ra...

  3. Sample Design.

    ERIC Educational Resources Information Center

    Ross, Kenneth N.

    1987-01-01

    This article considers various kinds of probability and non-probability samples in both experimental and survey studies. Throughout, how a sample is chosen is stressed. Size alone is not the determining consideration in sample selection. Good samples do not occur by accident; they are the result of a careful design. (Author/JAZ)

  4. Not all brains are made the same: new views on brain scaling in evolution.

    PubMed

    Herculano-Houzel, Suzana

    2011-01-01

    fashion, with relatively constant nonneuronal cell densities. As a result, while brain size can no longer be considered a proxy for the number of brain neurons across mammalian brains in general, it is actually a very good proxy for the number of nonneuronal cells in the brain. Together, these data point to developmental mechanisms that underlie evolutionary changes in brain size in mammals: while the rules that determine how neurons are added to the brain during development have been largely free to vary in mammalian evolution across clades, the rules that determine how other cells are added in development have been mostly constrained and to this day remain largely similar both across brain structures and across mammalian groups. PMID:21691045

  5. Treat Medication Samples with Respect

    MedlinePlus

    ... can be expected. If you receive an antibiotic sample, you may need to add water to make a liquid suspension. This should be ... very carefully, as adding the improper amount of water will result in a ... expiration date on the package, as samples may be stored for long periods of time ...

  6. The New York Times ad.

    PubMed

    Hunt, M E; Kissling, F

    1993-01-01

    Feminization of patriarchal institutions is necessary in order to eliminate the exclusivity and mutuality of hierarchical, gender, class, and race stratification. The aim of this paper is to explain the history and activities surrounding the New York Times ad on Sunday, October 7, 1984 (the Catholic Statement on Pluralism and Abortion signed by Barbara Ferraro and Patricia Hussey of the Sisters of Note Dame de Namur, Rose Dominic Trapasso of the Maryknoll Sisters, and 67 other signers). The significance of this ad for Roman Catholic feminists and suggestions for new models of relationships between feminists is given. The Statement was written by Daniel Maguire and Frances Kissling and reviewed by 20 Roman Catholic ethicists. A sponsoring committee of early signers sought other support. Catholics for a Free Choice sponsored the funding for circulation of the Statement among professional societies, but not necessarily canonical communities. Publication of the entire statement in the Times was at the height of the presidential campaign. Conservative Bishops Bernard Law of Boston and John O'Connor of Boston publicly denounced Ferraro's position. The first institutional church response came on November 14, 1984, and stated that the Statement was personal opinion and contradictory to clear and constant church teachings about abortion. On November 30, 1984, Cardinal Jean Jerome Hamer of the Congregation for Religious and Secular Institutes responded to most presidents of canonical communities to request a public retraction from signers under threat of dismissal. The issue was obedience to the church. Several members of the canonical community and priests published retractions; negotiations with the Vatican began. Freedom of conscience and empowerment of canonical communities, as agents of their own lives, were given as reasons for the challenge to paternalism. The response was that women were subject to obedience within their communities and had taken public vows and were

  7. Vision's Brain.

    ERIC Educational Resources Information Center

    Miller, Julie Ann

    1978-01-01

    The functional architecture of the primary visual cortex has been explored by monitoring the responses of individual brain cells to visual stimuli. A combination of anatomical and physiological techniques reveals groups of functionally related cells, juxtaposed and superimposed, in a sometimes complex, but presumably efficient, structure. (BB)

  8. Smart Brains.

    ERIC Educational Resources Information Center

    Jones, Rebecca

    1995-01-01

    New techniques have opened windows to the brain. Although the biochemistry of learning remains largely a mystery, the following findings seem to have clear implications for education: (1) the importance of early-learning opportunities for the very young; (2) the connection between music and abstract reasoning; and (3) the importance of good…

  9. Framingham Coronary Heart Disease Risk Score Can be Predicted from Structural Brain Images in Elderly Subjects

    PubMed Central

    Rondina, Jane Maryam; Squarzoni, Paula; Souza-Duran, Fabio Luis; Tamashiro-Duran, Jaqueline Hatsuko; Scazufca, Marcia; Menezes, Paulo Rossi; Vallada, Homero; Lotufo, Paulo A.; de Toledo Ferraz Alves, Tania Correa; Busatto Filho, Geraldo

    2014-01-01

    Recent literature has presented evidence that cardiovascular risk factors (CVRF) play an important role on cognitive performance in elderly individuals, both those who are asymptomatic and those who suffer from symptoms of neurodegenerative disorders. Findings from studies applying neuroimaging methods have increasingly reinforced such notion. Studies addressing the impact of CVRF on brain anatomy changes have gained increasing importance, as recent papers have reported gray matter loss predominantly in regions traditionally affected in Alzheimer’s disease (AD) and vascular dementia in the presence of a high degree of cardiovascular risk. In the present paper, we explore the association between CVRF and brain changes using pattern recognition techniques applied to structural MRI and the Framingham score (a composite measure of cardiovascular risk largely used in epidemiological studies) in a sample of healthy elderly individuals. We aim to answer the following questions: is it possible to decode (i.e., to learn information regarding cardiovascular risk from structural brain images) enabling individual predictions? Among clinical measures comprising the Framingham score, are there particular risk factors that stand as more predictable from patterns of brain changes? Our main findings are threefold: (i) we verified that structural changes in spatially distributed patterns in the brain enable statistically significant prediction of Framingham scores. This result is still significant when controlling for the presence of the APOE 4 allele (an important genetic risk factor for both AD and cardiovascular disease). (ii) When considering each risk factor singly, we found different levels of correlation between real and predicted factors; however, single factors were not significantly predictable from brain images when considering APOE4 allele presence as covariate. (iii) We found important gender differences, and the possible causes of that finding are discussed. PMID

  10. Myths & Facts about Value-Added Analysis

    ERIC Educational Resources Information Center

    TNTP, 2011

    2011-01-01

    This paper presents myths as well as facts about value-added analysis. These myths include: (1) "Value-added isn't fair to teachers who work in high-need schools, where students tend to lag far behind academically"; (2) "Value-added scores are too volatile from year-to-year to be trusted"; (3) "There's no research behind value-added"; (4) "Using…

  11. Condom ads promote illicit sex.

    PubMed

    Kippley, J F

    1994-01-01

    Written in 1987, this opinion was republished in the wake of US President Bill Clinton's AIDS prevention media campaign promoting condom use which began January 1994, targeted at young adults aged 18-25. The author staunchly opposes condom use even though he admits that people do not consider abstinence from sex to be a serious option for the prevention of HIV/STD infection. He believes that there is no moral use of sex with a condom and that condoms have always been a sign of immorality, be it prostitution, adultery, fornication, or marital contraception. Likewise, the author laments the success enjoyed by Planned Parenthood in achieving the social acceptance of marital contraception and sex outside of marriage. The complete social acceptance of homosexual activity, however, remains to be achieved. Magazines, newspapers, and television receive income in exchange for publishing or airing advertisements. Finding offensive advertisements which promote the use of condoms against HIV infection, the author recommends writing letters of complaint to the responsible media sources. If the television stations or publications in question continue to advertise condoms to the public, stop watching them or end one's subscriptions to the particular printed media. Such action taken collectively among many individuals will reduce product sales and income, and potentially sway corporate policy against condom ads. PMID:12345946

  12. Condom ads promote illicit sex.

    PubMed

    Kippley, J F

    1994-01-01

    Written in 1987, this opinion was republished in the wake of US President Bill Clinton's AIDS prevention media campaign promoting condom use which began January 1994, targeted at young adults aged 18-25. The author staunchly opposes condom use even though he admits that people do not consider abstinence from sex to be a serious option for the prevention of HIV/STD infection. He believes that there is no moral use of sex with a condom and that condoms have always been a sign of immorality, be it prostitution, adultery, fornication, or marital contraception. Likewise, the author laments the success enjoyed by Planned Parenthood in achieving the social acceptance of marital contraception and sex outside of marriage. The complete social acceptance of homosexual activity, however, remains to be achieved. Magazines, newspapers, and television receive income in exchange for publishing or airing advertisements. Finding offensive advertisements which promote the use of condoms against HIV infection, the author recommends writing letters of complaint to the responsible media sources. If the television stations or publications in question continue to advertise condoms to the public, stop watching them or end one's subscriptions to the particular printed media. Such action taken collectively among many individuals will reduce product sales and income, and potentially sway corporate policy against condom ads.

  13. 27 CFR 19.456 - Adding denaturants.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Adding denaturants. 19.456... Denaturation § 19.456 Adding denaturants. Denaturants and spirits shall be mixed in packages, tanks, or bulk... proprietor shall submit a flow diagram of the intended process or method of adding denaturants. (Sec....

  14. 16 CFR 460.18 - Insulation ads.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Insulation ads. 460.18 Section 460.18 Commercial Practices FEDERAL TRADE COMMISSION TRADE REGULATION RULES LABELING AND ADVERTISING OF HOME INSULATION § 460.18 Insulation ads. (a) If your ad gives an R-value, you must give the type of insulation...

  15. 16 CFR 460.18 - Insulation ads.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 1 2012-01-01 2012-01-01 false Insulation ads. 460.18 Section 460.18 Commercial Practices FEDERAL TRADE COMMISSION TRADE REGULATION RULES LABELING AND ADVERTISING OF HOME INSULATION § 460.18 Insulation ads. (a) If your ad gives an R-value, you must give the type of insulation...

  16. 16 CFR 460.18 - Insulation ads.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 1 2013-01-01 2013-01-01 false Insulation ads. 460.18 Section 460.18 Commercial Practices FEDERAL TRADE COMMISSION TRADE REGULATION RULES LABELING AND ADVERTISING OF HOME INSULATION § 460.18 Insulation ads. (a) If your ad gives an R-value, you must give the type of insulation...

  17. 16 CFR 460.18 - Insulation ads.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 1 2014-01-01 2014-01-01 false Insulation ads. 460.18 Section 460.18 Commercial Practices FEDERAL TRADE COMMISSION TRADE REGULATION RULES LABELING AND ADVERTISING OF HOME INSULATION § 460.18 Insulation ads. (a) If your ad gives an R-value, you must give the type of insulation...

  18. 16 CFR 460.18 - Insulation ads.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 1 2011-01-01 2011-01-01 false Insulation ads. 460.18 Section 460.18 Commercial Practices FEDERAL TRADE COMMISSION TRADE REGULATION RULES LABELING AND ADVERTISING OF HOME INSULATION § 460.18 Insulation ads. (a) If your ad gives an R-value, you must give the type of insulation...

  19. New Features in the ADS Abstract Service

    NASA Technical Reports Server (NTRS)

    Eichhorn, Guenther; Accomazzi, Alberto; Grant, Carolyn S.; Kurtz, Michael J.; Henneken, Edwin A.; Thompson, Donna M.; Murray, Stephen S.

    2005-01-01

    The NASA-ADS Abstract Service provides a sophisticated search capability for the literature in Astronomy, Planetary Sciences, Physics/Geophysics, and Space Instrumentation. The ADS is funded by NASA and access to the ADS services is free to anybody world-wide without restrictions. It allows the user to search the literature by author, title, and abstract text.

  20. Value Added and Other Related Matters.

    ERIC Educational Resources Information Center

    Whitla, Dean K.

    The term "value added" refers to the assessment of the amount of learning that takes place during the college years. Two experiments, Value Added I and Value Added II, attempted to measure college students' attainment of eight liberal education objectives: (1) writing ability; (2) analytical ability; (3) sensitivity to ethics, morals, and values;…

  1. Understanding Brain Tumors

    MedlinePlus

    ... to Know About Brain Tumors . What is a Brain Tumor? A brain tumor is an abnormal growth
 ... Tumors” from Frankly Speaking Frankly Speaking About Cancer: Brain Tumors Download the full book Questions to ask ...

  2. Brain Tumors (For Parents)

    MedlinePlus

    ... Story" 5 Things to Know About Zika & Pregnancy Brain Tumors KidsHealth > For Parents > Brain Tumors Print A ... radiation therapy or chemotherapy, or both. Types of Brain Tumors There are many different types of brain ...

  3. Brain Tumor Diagnosis

    MedlinePlus

    ... Types of Brain Scans X-rays Laboratory Tests DNA Profiling Biopsy Procedure Malignant and Benign Brain Tumors Tumor ... Types of Brain Scans X-rays Laboratory Tests DNA Profiling Biopsy Procedure Malignant and Benign Brain Tumors Tumor ...

  4. Altered Expression of Diabetes-Related Genes in Alzheimer's Disease Brains: The Hisayama Study

    PubMed Central

    Hokama, Masaaki; Oka, Sugako; Leon, Julio; Ninomiya, Toshiharu; Honda, Hiroyuki; Sasaki, Kensuke; Iwaki, Toru; Ohara, Tomoyuki; Sasaki, Tomio; LaFerla, Frank M.; Kiyohara, Yutaka; Nakabeppu, Yusaku

    2014-01-01

    Diabetes mellitus (DM) is considered to be a risk factor for dementia including Alzheimer's disease (AD). However, the molecular mechanism underlying this risk is not well understood. We examined gene expression profiles in postmortem human brains donated for the Hisayama study. Three-way analysis of variance of microarray data from frontal cortex, temporal cortex, and hippocampus was performed with the presence/absence of AD and vascular dementia, and sex, as factors. Comparative analyses of expression changes in the brains of AD patients and a mouse model of AD were also performed. Relevant changes in gene expression identified by microarray analysis were validated by quantitative real-time reverse-transcription polymerase chain reaction and western blotting. The hippocampi of AD brains showed the most significant alteration in gene expression profile. Genes involved in noninsulin-dependent DM and obesity were significantly altered in both AD brains and the AD mouse model, as were genes related to psychiatric disorders and AD. The alterations in the expression profiles of DM-related genes in AD brains were independent of peripheral DM-related abnormalities. These results indicate that altered expression of genes related to DM in AD brains is a result of AD pathology, which may thereby be exacerbated by peripheral insulin resistance or DM. PMID:23595620

  5. High energy QCD from Planckian scattering in AdS space and the Froissart bound

    SciTech Connect

    Kang, Kyungsik; Nastase, Horatiu

    2005-11-15

    We reanalyze high-energy QCD scattering regimes from scattering in cutoff AdS space via gravity-gauge dualities (a la Polchinski-Strassler). We look at 't Hooft scattering, Regge behavior, and black hole creation in AdS space. Black hole creation in the gravity dual is analyzed via gravitational shockwave collisions. We prove the saturation of the QCD Froissart unitarity bound, corresponding to the creation of black holes of AdS size, as suggested by Giddings.

  6. Capillary sample

    MedlinePlus

    ... using capillary blood sampling. Disadvantages to capillary blood sampling include: Only a limited amount of blood can be drawn using this method. The procedure has some risks (see below). Capillary ...

  7. Martian 'Brain'

    NASA Technical Reports Server (NTRS)

    2004-01-01

    5 May 2004 Most middle-latitude craters on Mars have strange landforms on their floors. Often, the floors have pitted and convoluted features that lack simple explanation. In this case, the central part of the crater floor shown in this 2004 Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image bears some resemblance to the folded nature of a brain. Or not. It depends upon the 'eye of the beholder,' perhaps. The light-toned 'ring' around the 'brain' feature is more easily explained--windblown ripples and dunes. The crater occurs near 33.1oS, 91.2oW, and is illuminated from the upper left. The picture covers an area about 3 km (1.9 mi) across.

  8. Silicon Brains

    NASA Astrophysics Data System (ADS)

    Hoefflinger, Bernd

    Beyond the digital neural networks of Chap. 16, the more radical mapping of brain-like structures and processes into VLSI substrates has been pioneered by Carver Mead more than 30 years ago [1]. The basic idea was to exploit the massive parallelism of such circuits and to create low-power and fault-tolerant information-processing systems. Neuromorphic engineering has recently seen a revival with the availability of deep-submicron CMOS technology, which allows for the construction of very-large-scale mixed-signal systems combining local analog processing in neuronal cells with binary signalling via action potentials. Modern implementations are able to reach the complexity-scale of large functional units of the human brain, and they feature the ability to learn by plasticity mechanisms found in neuroscience. Combined with high-performance programmable logic and elaborate software tools, such systems are currently evolving into user-configurable non-von-Neumann computing systems, which can be used to implement and test novel computational paradigms. The chapter introduces basic properties of biological brains with up to 200 Billion neurons and their 1014 synapses, where action on a synapse takes ˜10 ms and involves an energy of ˜10 fJ. We outline 10x programs on neuromorphic electronic systems in Europe and the USA, which are intended to integrate 108 neurons and 1012 synapses, the level of a cat's brain, in a volume of 1 L and with a power dissipation <1 kW. For a balanced view on intelligence, we references Hawkins' view to first perceive the task and then design an intelligent technical response.

  9. Brain imaging

    SciTech Connect

    Bradshaw, J.R.

    1989-01-01

    This book presents a survey of the various imaging tools with examples of the different diseases shown best with each modality. It includes 100 case presentations covering the gamut of brain diseases. These examples are grouped according to the clinical presentation of the patient: headache, acute headache, sudden unilateral weakness, unilateral weakness of gradual onset, speech disorders, seizures, pituitary and parasellar lesions, sensory disorders, posterior fossa and cranial nerve disorders, dementia, and congenital lesions.

  10. Influence of Education on the Pattern of Cognitive Deterioration in Ad Patients: The Cognitive Reserve Hypothesis

    ERIC Educational Resources Information Center

    Carret, N.L.; Auriacombe, S.; Letenneur, L.; Bergua, V.; Dartigues, J.F.; Fabrigoule, C.

    2005-01-01

    The cognitive reserve hypothesis proposes that a high educational level could delay the clinical expression of Alzheimer's disease (AD) although neuropathologic changes develop in the brain. Therefore, some studies have reported that when the clinical signs of the disease emerge, high-educated patients may decline more rapidly than low-educated…

  11. Animating Brains

    PubMed Central

    Borck, Cornelius

    2016-01-01

    A recent paper famously accused the rising field of social neuroscience of using faulty statistics under the catchy title ‘Voodoo Correlations in Social Neuroscience’. This Special Issue invites us to take this claim as the starting point for a cross-cultural analysis: in which meaningful ways can recent research in the burgeoning field of functional imaging be described as, contrasted with, or simply compared to animistic practices? And what light does such a reading shed on the dynamics and effectiveness of a century of brain research into higher mental functions? Reviewing the heated debate from 2009 around recent trends in neuroimaging as a possible candidate for current instances of ‘soul catching’, the paper will then compare these forms of primarily image-based brain research with older regimes, revolving around the deciphering of the brain’s electrical activity. How has the move from a decoding paradigm to a representational regime affected the conceptualisation of self, psyche, mind and soul (if there still is such an entity)? And in what ways does modern technoscience provide new tools for animating brains? PMID:27292322

  12. Brain Endothelial Cells Synthesize Neurotoxic Thrombin in Alzheimer’s Disease

    PubMed Central

    Yin, Xiangling; Wright, Jill; Wall, Trevor; Grammas, Paula

    2010-01-01

    Alzheimer’s disease (AD) is characterized by neuronal death; thus, identifying neurotoxic proteins and their source is central to understanding and treating AD. The multifunctional protease thrombin is neurotoxic and found in AD senile plaques. The objective of this study was to determine whether brain endothelial cells can synthesize thrombin and thus be a source of this neurotoxin in AD brains. Microvessels were isolated from AD patient brains and from age-matched controls. Reverse transcription-PCR demonstrated that thrombin message was highly expressed in microvessels from AD brains but was not detectable in control vessels. Similarly, Western blot analysis of microvessels showed that the thrombin protein was highly expressed in AD- but not control-derived microvessels. In addition, high levels of thrombin were detected in cerebrospinal fluid obtained from AD but not control patients, and sections from AD brains showed reactivity to thrombin antibody in blood vessel walls but not in vessels from controls. Finally, we examined the ability of brain endothelial cells in culture to synthesize thrombin and showed that oxidative stress or cell signaling perturbations led to increased expression of thrombin mRNA in these cells. The results demonstrate, for the first time, that brain endothelial cells can synthesize thrombin, and suggest that novel therapeutics targeting vascular stabilization that prevent or decrease release of thrombin could prove useful in treating this neurodegenerative disease. PMID:20150433

  13. Imaging Nicotine in Rat Brain Tissue by Use of Nanospray Desorption Electrospray Ionization Mass Spectrometry

    SciTech Connect

    Lanekoff, Ingela T.; Thomas, Mathew; Carson, James P.; Smith, Jordan N.; Timchalk, Charles; Laskin, Julia

    2013-01-15

    Imaging mass spectrometry offers simultaneous detection of drugs, drug metabolites and endogenous substances in a single experiment. This is important when evaluating effects of a drug on a complex organ system such as the brain, where there is a need to understand how regional drug distribution impacts function. Nicotine is an addictive drug and its action in the brain is of high interest. Here we use nanospray desorption electrospray ionization, nano-DESI, imaging to discover the localization of nicotine in rat brain tissue after in vivo administration of nicotine. Nano-DESI is a new ambient technique that enables spatially-resolved analysis of tissue samples without special sample pretreatment. We demonstrate high sensitivity of nano-DESI imaging that enables detection of only 0.7 fmole nicotine per pixel in the complex brain matrix. Furthermore, by adding deuterated nicotine to the solvent, we examined how matrix effects, ion suppression, and normalization affect the observed nicotine distribution. Finally, we provide preliminary results suggesting that nicotine localizes to the hippocampal substructure called dentate gyrus.

  14. Adaptive Dimensionality Reduction with Semi-Supervision (AdDReSS): Classifying Multi-Attribute Biomedical Data

    PubMed Central

    Romo Bucheli, David Edmundo; Madabhushi, Anant

    2016-01-01

    Medical diagnostics is often a multi-attribute problem, necessitating sophisticated tools for analyzing high-dimensional biomedical data. Mining this data often results in two crucial bottlenecks: 1) high dimensionality of features used to represent rich biological data and 2) small amounts of labelled training data due to the expense of consulting highly specific medical expertise necessary to assess each study. Currently, no approach that we are aware of has attempted to use active learning in the context of dimensionality reduction approaches for improving the construction of low dimensional representations. We present our novel methodology, AdDReSS (Adaptive Dimensionality Reduction with Semi-Supervision), to demonstrate that fewer labeled instances identified via AL in embedding space are needed for creating a more discriminative embedding representation compared to randomly selected instances. We tested our methodology on a wide variety of domains ranging from prostate gene expression, ovarian proteomic spectra, brain magnetic resonance imaging, and breast histopathology. Across these various high dimensional biomedical datasets with 100+ observations each and all parameters considered, the median classification accuracy across all experiments showed AdDReSS (88.7%) to outperform SSAGE, a SSDR method using random sampling (85.5%), and Graph Embedding (81.5%). Furthermore, we found that embeddings generated via AdDReSS achieved a mean 35.95% improvement in Raghavan efficiency, a measure of learning rate, over SSAGE. Our results demonstrate the value of AdDReSS to provide low dimensional representations of high dimensional biomedical data while achieving higher classification rates with fewer labelled examples as compared to without active learning. PMID:27421116

  15. Controlling self-sustained spiking activity by adding or removing one network link

    NASA Astrophysics Data System (ADS)

    Xu, Kesheng; Huang, Wenwen; Li, Baowen; Dhamala, Mukesh; Liu, Zonghua

    2013-06-01

    Being able to control the neuronal spiking activity in specific brain regions is central to a treatment scheme in several brain disorders such as epileptic seizures, mental depression, and Parkinson's diseases. Here, we present an approach for controlling self-sustained oscillations by adding or removing one directed network link in coupled neuronal oscillators, in contrast to previous approaches of adding stimuli or noise. We find that such networks can exhibit a variety of activity patterns such as on-off switch, sustained spikes, and short-term spikes. We derive the condition for a specific link to be the controller of the on-off effect. A qualitative analysis is provided to facilitate the understanding of the mechanism for spiking activity by adding one link. Our findings represent the first report on generating spike activity with the addition of only one directed link to a network and provide a deeper understanding of the microscopic roots of self-sustained spiking.

  16. Triptolide treatment reduces Alzheimer's disease (AD)-like pathology through inhibition of BACE1 in a transgenic mouse model of AD.

    PubMed

    Wang, Qi; Xiao, Bing; Cui, Shuqin; Song, Hailong; Qian, Yanjing; Dong, Lin; An, Haiting; Cui, Yanqiu; Zhang, Wenjing; He, Yi; Zhang, Jianliang; Yang, Jian; Zhang, Feilong; Hu, Guanzheng; Gong, Xiaoli; Yan, Zhen; Zheng, Yan; Wang, Xiaomin

    2014-12-01

    The complex pathogenesis of Alzheimer's disease (AD) involves multiple contributing factors, including amyloid β (Aβ) peptide accumulation, inflammation and oxidative stress. Effective therapeutic strategies for AD are still urgently needed. Triptolide is the major active compound extracted from Tripterygium wilfordii Hook.f., a traditional Chinese medicinal herb that is commonly used to treat inflammatory diseases. The 5-month-old 5XFAD mice, which carry five familial AD mutations in the β-amyloid precursor protein (APP) and presenilin-1 (PS1) genes, were treated with triptolide for 8 weeks. We observed enhanced spatial learning performances, and attenuated Aβ production and deposition in the brain. Triptolide also inhibited the processing of amyloidogenic APP, as well as the expression of βAPP-cleaving enzyme-1 (BACE1) both in vivo and in vitro. In addition, triptolide exerted anti-inflammatory and anti-oxidative effects on the transgenic mouse brain. Triptolide therefore confers protection against the effects of AD in our mouse model and is emerging as a promising therapeutic candidate drug for AD.

  17. Regional white matter hyperintensities: aging, AD risk, and cognitive function

    PubMed Central

    Birdsill, Alex C; Koscik, Rebecca L; Jonaitis, Erin M; Johnson, Sterling C; Okonkwo, Ozioma C; Hermann, Bruce P; LaRue, Asenath; Sager, Mark A; Bendlin, Barbara B

    2013-01-01

    White matter hyperintensities (WMH) of presumed vascular origin as seen on T2-weighted fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI), are known to increase with age and are elevated in Alzheimer’s disease (AD). The cognitive implications of these common markers are not well understood. Previous research has primarily focused on global measures of WMH burden and broad localizations that contain multiple white matter tracts. The aims of this study were to determine the pattern of WMH accumulation with age, risk for AD, and the relationship with cognitive function utilizing a voxel-wise analysis capable of identifying specific white matter regions. Three hundred and forty-nine participants underwent T1-weighted and high-resolution T2FLAIR MRI and neuropsychological testing. Increasing age and lower cognitive speed and flexibility (a component of executive function), were both significantly associated with regional WMH throughout the brain. When age was controlled, lower cognitive speed and flexibility was independently associated with WMH in the superior corona radiata. APOE4 and parental family history of AD were not associated with higher burden of WMH. The results contribute to a larger body of literature suggesting that white matter measures are linked with processing speed, and illustrate the utility of voxel-wise analysis in understanding the effect of lesion location on cognitive function. PMID:24199958

  18. LWR (Light Water Reactor) power plant simulations using the AD10 and AD100 systems

    SciTech Connect

    Wulff, W.; Cheng, H.S.; Chien, C.J.; Jang, J.Y.; Lin, H.C.; Mallen, A.N.; Wang, S.J.; Institute of Nuclear Energy Research, Lung-Tan; Tawian Power Co., Taipei; Brookhaven National Lab., Upton, NY; Institute of Nuclear Energy Research, Lung-Tan )

    1989-01-01

    Boiling (BWR) and Pressurized (PWR) Water Reactor Power Plants are being simulated at BNL with the AD10 and AD100 Peripheral Processor Systems. The AD10 system has been used for BWR simulations since 1984 for safety analyses, emergency training and optimization studies. BWR simulation capabilities have been implemented recently on the AD100 system and PWR simulation capabilities are currently being developed under the auspices of international cooperation. Modeling and simulation methods are presented with emphasis on the simulation of the Nuclear Steam Supply System. Results are presented for BWR simulation and performance characteristics are compared of the AD10 and AD100 systems. It will be shown that the AD100 simulates two times faster than two AD10 processors operating in parallel and that the computing capacity of one AD100 (with FMU processor) is twice as large as that of two AD10 processors. 9 refs., 5 figs., 1 tab.

  19. Powder sampling.

    PubMed

    Venables, Helena J; Wells, J I

    2002-01-01

    The factors involved when sampling powder mixes have been reviewed. The various methods are evaluated (manual, automatic, and sub-sampling) and the errors incurred are discussed. Certain rules have been applied to various samplers and their suitability for powder mixtures are described. The spinning riffler is apparently the most suitable, while the use of sample thieves should be avoided due to error and bias.

  20. Sampling Development

    PubMed Central

    Adolph, Karen E.; Robinson, Scott R.

    2011-01-01

    Research in developmental psychology requires sampling at different time points. Accurate depictions of developmental change provide a foundation for further empirical studies and theories about developmental mechanisms. However, overreliance on widely spaced sampling intervals in cross-sectional and longitudinal designs threatens the validity of the enterprise. This article discusses how to sample development in order to accurately discern the shape of developmental change. The ideal solution is daunting: to summarize behavior over 24-hour intervals and collect daily samples over the critical periods of change. We discuss the magnitude of errors due to undersampling, and the risks associated with oversampling. When daily sampling is not feasible, we offer suggestions for sampling methods that can provide preliminary reference points and provisional sketches of the general shape of a developmental trajectory. Denser sampling then can be applied strategically during periods of enhanced variability, inflections in the rate of developmental change, or in relation to key events or processes that may affect the course of change. Despite the challenges of dense repeated sampling, researchers must take seriously the problem of sampling on a developmental time scale if we are to know the true shape of developmental change. PMID:22140355

  1. Inseparability of photon-added Gaussian states

    SciTech Connect

    Li Hongrong; Li Fuli; Zhu Shiyao

    2007-06-15

    The inseparability of photon-added Gaussian states which are generated from two-mode Gaussian states by adding photons is investigated. According to the established inseparability conditions [New J. Phys. 7, 211 (2005); Phys. Rev. Lett. 96, 050503 (2006)], we find that even if a two-mode Gaussian state is separable, the photon-added Gaussian state becomes entangled when the purity of the Gaussian state is larger than a certain value. The lower bound of entanglement of symmetric photon-added Gaussian states is derived. The result shows that entanglement of the photon-added Gaussian states is involved with high-order moment correlations. We find that fidelity of teleporting coherent states cannot be raised by employing the photon-added Gaussian states as a quantum channel of teleportation.

  2. Increased selenoprotein P in choroid plexus and cerebrospinal fluid in Alzheimer's disease brain.

    PubMed

    Rueli, Rachel H L H; Parubrub, Arlene C; Dewing, Andrea S T; Hashimoto, Ann C; Bellinger, Miyoko T; Weeber, Edwin J; Uyehara-Lock, Jane H; White, Lon R; Berry, Marla J; Bellinger, Frederick P

    2015-01-01

    Subjects with Alzheimer's disease (AD) have elevated brain levels of the selenium transporter selenoprotein P (Sepp1). We investigated if this elevation results from increased release of Sepp1 from the choroid plexus (CP). Sepp1 is significantly increased in CP from AD brains in comparison to non-AD brains. Sepp1 localizes to the trans-Golgi network within CP epithelia, where it is processed for secretion. The cerebrospinal fluid from AD subjects also contains increased levels Sepp1 in comparison to non-AD subjects. These findings suggest that AD pathology induces increased levels of Sepp1 within CP epithelia for release into the cerebrospinal fluid to ultimately increase brain selenium.

  3. Increased Selenoprotein P in Choroid Plexus and Cerebrospinal Fluid in Alzheimer’s Disease Brain

    PubMed Central

    Rueli, Rachel H.L.H.; Parubrub, Arlene C.; Dewing, Andrea S.T.; Hashimoto, Ann C.; Bellinger, Miyoko T.; Weeber, Edwin J.; Uyehara-Lock, Jane H.; White, Lon R.; Berry, Marla J.; Bellinger, Frederick P.

    2015-01-01

    Subjects with Alzheimer’s disease (AD) have elevated brain levels of the selenium transporter selenoprotein P (Sepp1). We investigated if this elevation results from increased release of Sepp1 from the choroid plexus (CP). Sepp1 is significantly increased in CP from AD brains in comparison to non-AD brains. Sepp1 localizes to the trans-Golgi network within CP epithelia, where it is processed for secretion. The cerebrospinal fluid from AD subjects also contains increased levels Sepp1 in comparison to non-AD subjects. These findings suggest that AD pathology induces increased levels of Sepp1 within CP epithelia for release into the cerebrospinal fluid to ultimately increase brain selenium. PMID:25298198

  4. Brain Imaging

    PubMed Central

    Racine, Eric; Bar-Ilan, Ofek; Illes, Judy

    2007-01-01

    Advances in neuroscience are increasingly intersecting with issues of ethical, legal, and social interest. This study is an analysis of press coverage of an advanced technology for brain imaging, functional magnetic resonance imaging, that has gained significant public visibility over the past ten years. Discussion of issues of scientific validity and interpretation dominated over ethical content in both the popular and specialized press. Coverage of research on higher order cognitive phenomena specifically attributed broad personal and societal meaning to neuroimages. The authors conclude that neuroscience provides an ideal model for exploring science communication and ethics in a multicultural context. PMID:17330151

  5. Oxidative stability of yogurt with added lutein dye.

    PubMed

    Domingos, L D; Xavier, A A O; Mercadante, A Z; Petenate, A J; Jorge, R A; Viotto, W H

    2014-02-01

    This study evaluated the effect of adding lutein dye on the oxidative stability of yogurt during 35 d of refrigerated storage, in the presence and absence of light. Yogurts manufactured without and with the equivalent of 1.5mg of lutein in 120 g of the final product were characterized for their total carotenoid and riboflavin contents, and the behaviors of both riboflavin and lutein were monitored during storage. A decrease in riboflavin content occurred, with concurrent appearance of its derived-oxidation products in the yogurts without added lutein and exposed to light during storage. The yogurts with added lutein dye showed constant lutein and riboflavin contents throughout storage both for the samples stored under light and for those stored in the dark. Yogurts (120 g) with the addition of 0.5, 1.5, and 2.5mg of lutein dye were evaluated for their sensory acceptance, and the statistical analysis showed no differences between the samples for the attributes of aroma and flavor. These results indicate that the added lutein remained stable throughout the storage period and conferred protection for the riboflavin against photooxidation, preserving the quality of the yogurts.

  6. Sampling Development

    ERIC Educational Resources Information Center

    Adolph, Karen E.; Robinson, Scott R.

    2011-01-01

    Research in developmental psychology requires sampling at different time points. Accurate depictions of developmental change provide a foundation for further empirical studies and theories about developmental mechanisms. However, overreliance on widely spaced sampling intervals in cross-sectional and longitudinal designs threatens the validity of…

  7. Properties of reformulated hot dog sausage without added nitrites during chilled storage.

    PubMed

    Ruiz-Capillas, C; Herrero, A M; Tahmouzi, S; Razavi, S H; Triki, M; Rodríguez-Salas, L; Samcová, K; Jiménez-Colmenero, F

    2016-01-01

    The aim of this study was to assess the effect of a complete nitrite replacement strategy using celery, carmine, sodium lactate and orange dietary fibre combined with vitamins C and E, on the quality characteristics (technological, sensorial and safety properties) of hot dog sausages (five samples) during chilled storage (2 ± 1℃ 60 days). Nitrite replacers (combined with vitamins C and E) presented antioxidant activity, reducing lipid oxidation in reformulated samples. At the end of storage redness (a*) was similar in the control sample (with added nitrite) and in the sample without added nitrite. Sensory evaluation detected no significant difference between samples with and without added nitrite. All the reformulated samples were judged acceptable by the panellists. At the end of storage, the control sample contained more than four times as much residual nitrite as the reformulated samples. Growth of presumptive Clostridium perfringens was not observed in any of the samples. Samples without added nitrite had longer shelf-lives than control sausage. Samples containing 0.1% vitamin C registered the lowest microbiological levels. This strategy could be a good alternative to reduce and/or eliminate added nitrite in hot dog sausages.

  8. Properties of reformulated hot dog sausage without added nitrites during chilled storage.

    PubMed

    Ruiz-Capillas, C; Herrero, A M; Tahmouzi, S; Razavi, S H; Triki, M; Rodríguez-Salas, L; Samcová, K; Jiménez-Colmenero, F

    2016-01-01

    The aim of this study was to assess the effect of a complete nitrite replacement strategy using celery, carmine, sodium lactate and orange dietary fibre combined with vitamins C and E, on the quality characteristics (technological, sensorial and safety properties) of hot dog sausages (five samples) during chilled storage (2 ± 1℃ 60 days). Nitrite replacers (combined with vitamins C and E) presented antioxidant activity, reducing lipid oxidation in reformulated samples. At the end of storage redness (a*) was similar in the control sample (with added nitrite) and in the sample without added nitrite. Sensory evaluation detected no significant difference between samples with and without added nitrite. All the reformulated samples were judged acceptable by the panellists. At the end of storage, the control sample contained more than four times as much residual nitrite as the reformulated samples. Growth of presumptive Clostridium perfringens was not observed in any of the samples. Samples without added nitrite had longer shelf-lives than control sausage. Samples containing 0.1% vitamin C registered the lowest microbiological levels. This strategy could be a good alternative to reduce and/or eliminate added nitrite in hot dog sausages. PMID:25480689

  9. 3D characterization of brain atrophy in Alzheimer's disease and mild cognitive impairment using tensor-based morphometry.

    PubMed

    Hua, Xue; Leow, Alex D; Lee, Suh; Klunder, Andrea D; Toga, Arthur W; Lepore, Natasha; Chou, Yi-Yu; Brun, Caroline; Chiang, Ming-Chang; Barysheva, Marina; Jack, Clifford R; Bernstein, Matt A; Britson, Paula J; Ward, Chadwick P; Whitwell, Jennifer L; Borowski, Bret; Fleisher, Adam S; Fox, Nick C; Boyes, Richard G; Barnes, Josephine; Harvey, Danielle; Kornak, John; Schuff, Norbert; Boreta, Lauren; Alexander, Gene E; Weiner, Michael W; Thompson, Paul M

    2008-05-15

    Tensor-based morphometry (TBM) creates three-dimensional maps of disease-related differences in brain structure, based on nonlinearly registering brain MRI scans to a common image template. Using two different TBM designs (averaging individual differences versus aligning group average templates), we compared the anatomical distribution of brain atrophy in 40 patients with Alzheimer's disease (AD), 40 healthy elderly controls, and 40 individuals with amnestic mild cognitive impairment (aMCI), a condition conferring increased risk for AD. We created an unbiased geometrical average image template for each of the three groups, which were matched for sex and age (mean age: 76.1 years+/-7.7 SD). We warped each individual brain image (N=120) to the control group average template to create Jacobian maps, which show the local expansion or compression factor at each point in the image, reflecting individual volumetric differences. Statistical maps of group differences revealed widespread medial temporal and limbic atrophy in AD, with a lesser, more restricted distribution in MCI. Atrophy and CSF space expansion both correlated strongly with Mini-Mental State Exam (MMSE) scores and Clinical Dementia Rating (CDR). Using cumulative p-value plots, we investigated how detection sensitivity was influenced by the sample size, the choice of search region (whole brain, temporal lobe, hippocampus), the initial linear registration method (9- versus 12-parameter), and the type of TBM design. In the future, TBM may help to (1) identify factors that resist or accelerate the disease process, and (2) measure disease burden in treatment trials.

  10. Transcriptomics and mechanistic elucidation of Alzheimer's disease risk genes in the brain and in vitro models.

    PubMed

    Martiskainen, Henna; Viswanathan, Jayashree; Nykänen, Niko-Petteri; Kurki, Mitja; Helisalmi, Seppo; Natunen, Teemu; Sarajärvi, Timo; Kurkinen, Kaisa M A; Pursiheimo, Juha-Pekka; Rauramaa, Tuomas; Alafuzoff, Irina; Jääskeläinen, Juha E; Leinonen, Ville; Soininen, Hilkka; Haapasalo, Annakaisa; Huttunen, Henri J; Hiltunen, Mikko

    2015-02-01

    In this study, we have assessed the expression and splicing status of genes involved in the pathogenesis or affecting the risk of Alzheimer's disease (AD) in the postmortem inferior temporal cortex samples obtained from 60 subjects with varying degree of AD-related neurofibrillary pathology. These subjects were grouped based on neurofibrillary pathology into 3 groups: Braak stages 0-II, Braak stages III-IV, and Braak stages V-VI. We also examined the right frontal cortical biopsies obtained during life from 22 patients with idiopathic shunt-responding normal pressure hydrocephalus, a disease that displays similar pathologic alterations as seen in AD. These 22 patients were categorized according to dichotomized amyloid-β positive or negative pathology in the biopsies. We observed that the expression of FRMD4A significantly decreased, and the expression of MS4A6A significantly increased in relation to increasing AD-related neurofibrillary pathology. Moreover, the expression of 2 exons in both CLU and TREM2 significantly increased with increase in AD-related neurofibrillary pathology. However, a similar trend toward increased expression in CLU and TREM2 was observed with most of the studied exons, suggesting a global change in the expression rather than altered splicing. Correlation of gene expression with well-established AD-related factors, such as α-, β-, and γ-secretase activities, brain amyloid-β42 levels, and cerebrospinal fluid biomarkers, revealed a positive correlation between β-secretase activity and the expression of TREM2 and BIN1. In expression quantitative trait loci analysis, we did not detect significant effects of the risk alleles on gene expression or splicing. Analysis of the normal pressure hydrocephalus biopsies revealed no differences in the expression or splicing profiles of the studied genes between amyloid-β positive and negative patients. Using the protein-protein interaction-based in vitro pathway analysis tools, we found that

  11. Elevation of brain glucose and polyol-pathway intermediates with accompanying brain-copper deficiency in patients with Alzheimer’s disease: metabolic basis for dementia

    PubMed Central

    Xu, Jingshu; Begley, Paul; Church, Stephanie J.; Patassini, Stefano; McHarg, Selina; Kureishy, Nina; Hollywood, Katherine A.; Waldvogel, Henry J.; Liu, Hong; Zhang, Shaoping; Lin, Wanchang; Herholz, Karl; Turner, Clinton; Synek, Beth J.; Curtis, Maurice A.; Rivers-Auty, Jack; Lawrence, Catherine B.; Kellett, Katherine A. B.; Hooper, Nigel M.; Vardy, Emma R. L. C.; Wu, Donghai; Unwin, Richard D.; Faull, Richard L. M.; Dowsey, Andrew W.; Cooper, Garth J. S.

    2016-01-01

    Impairment of brain-glucose uptake and brain-copper regulation occurs in Alzheimer’s disease (AD). Here we sought to further elucidate the processes that cause neurodegeneration in AD by measuring levels of metabolites and metals in brain regions that undergo different degrees of damage. We employed mass spectrometry (MS) to measure metabolites and metals in seven post-mortem brain regions of nine AD patients and nine controls, and plasma-glucose and plasma-copper levels in an ante-mortem case-control study. Glucose, sorbitol and fructose were markedly elevated in all AD brain regions, whereas copper was correspondingly deficient throughout (all P < 0.0001). In the ante-mortem case-control study, by contrast, plasma-glucose and plasma-copper levels did not differ between patients and controls. There were pervasive defects in regulation of glucose and copper in AD brain but no evidence for corresponding systemic abnormalities in plasma. Elevation of brain glucose and deficient brain copper potentially contribute to the pathogenesis of neurodegeneration in AD. PMID:27276998

  12. Elevation of brain glucose and polyol-pathway intermediates with accompanying brain-copper deficiency in patients with Alzheimer's disease: metabolic basis for dementia.

    PubMed

    Xu, Jingshu; Begley, Paul; Church, Stephanie J; Patassini, Stefano; McHarg, Selina; Kureishy, Nina; Hollywood, Katherine A; Waldvogel, Henry J; Liu, Hong; Zhang, Shaoping; Lin, Wanchang; Herholz, Karl; Turner, Clinton; Synek, Beth J; Curtis, Maurice A; Rivers-Auty, Jack; Lawrence, Catherine B; Kellett, Katherine A B; Hooper, Nigel M; Vardy, Emma R L C; Wu, Donghai; Unwin, Richard D; Faull, Richard L M; Dowsey, Andrew W; Cooper, Garth J S

    2016-06-09

    Impairment of brain-glucose uptake and brain-copper regulation occurs in Alzheimer's disease (AD). Here we sought to further elucidate the processes that cause neurodegeneration in AD by measuring levels of metabolites and metals in brain regions that undergo different degrees of damage. We employed mass spectrometry (MS) to measure metabolites and metals in seven post-mortem brain regions of nine AD patients and nine controls, and plasma-glucose and plasma-copper levels in an ante-mortem case-control study. Glucose, sorbitol and fructose were markedly elevated in all AD brain regions, whereas copper was correspondingly deficient throughout (all P < 0.0001). In the ante-mortem case-control study, by contrast, plasma-glucose and plasma-copper levels did not differ between patients and controls. There were pervasive defects in regulation of glucose and copper in AD brain but no evidence for corresponding systemic abnormalities in plasma. Elevation of brain glucose and deficient brain copper potentially contribute to the pathogenesis of neurodegeneration in AD.

  13. Imaging the Gambling Brain.

    PubMed

    Balodis, I M; Potenza, M N

    2016-01-01

    Neuroimaging studies examining the neurobiological basis of gambling disorder (GD) have increased over the past decade. Functional magnetic resonance imaging studies during appetitive cue and reward processing tasks demonstrate altered functioning in frontostriatal brain areas, including the ventral striatum and the ventromedial prefrontal cortex. Findings suggest differences in how the anticipation and outcome of rewards are processed in individuals with GD. Future research requires larger sample sizes and should include appropriate clinical reference groups. Overall, studies to date highlight a common pathophysiology between substance-based addictions and GD, the latter offering a unique condition in which to examine nonchemical factors in addiction. PMID:27503450

  14. On shape dependence of holographic entanglement entropy in AdS4/CFT3

    NASA Astrophysics Data System (ADS)

    Fonda, Piermarco; Seminara, Domenico; Tonni, Erik

    2015-12-01

    We study the finite term of the holographic entanglement entropy of finite domains with smooth shapes and for four dimensional gravitational backgrounds. Analytic expressions depending on the unit vectors normal to the minimal area surface are obtained for both stationary and time dependent spacetimes. The special cases of AdS4, asymptotically AdS4 black holes, domain wall geometries and Vaidya-AdS backgrounds have been analysed explicitly. When the bulk spacetime is AdS4, the finite term is the Willmore energy of the minimal area surface viewed as a submanifold of the three dimensional flat Euclidean space. For the static spacetimes, some numerical checks involving spatial regions delimited by ellipses and non convex domains have been performed. In the case of AdS4, the infinite wedge has been also considered, recovering the known analytic formula for the coefficient of the logarithmic divergence.

  15. Plasma protein biomarkers of Alzheimer's disease endophenotypes in asymptomatic older twins: early cognitive decline and regional brain volumes.

    PubMed

    Kiddle, S J; Steves, C J; Mehta, M; Simmons, A; Xu, X; Newhouse, S; Sattlecker, M; Ashton, N J; Bazenet, C; Killick, R; Adnan, J; Westman, E; Nelson, S; Soininen, H; Kloszewska, I; Mecocci, P; Tsolaki, M; Vellas, B; Curtis, C; Breen, G; Williams, S C R; Lovestone, S; Spector, T D; Dobson, R J B

    2015-06-16

    There is great interest in blood-based markers of Alzheimer's disease (AD), especially in its pre-symptomatic stages. Therefore, we aimed to identify plasma proteins whose levels associate with potential markers of pre-symptomatic AD. We also aimed to characterise confounding by genetics and the effect of genetics on blood proteins in general. Panel-based proteomics was performed using SOMAscan on plasma samples from TwinsUK subjects who are asymptomatic for AD, measuring the level of 1129 proteins. Protein levels were compared with 10-year change in CANTAB-paired associates learning (PAL; n = 195), and regional brain volumes (n = 34). Replication of proteins associated with regional brain volumes was performed in 254 individuals from the AddNeuroMed cohort. Across all the proteins measured, genetic factors were found to explain ~26% of the variability in blood protein levels on average. The plasma level of the mitogen-activated protein kinase (MAPK) MAPKAPK5 protein was found to positively associate with the 10-year change in CANTAB-PAL in both the individual and twin difference context. The plasma level of protein MAP2K4 was found to suggestively associate negatively (Q < 0.1) with the volume of the left entorhinal cortex. Future studies will be needed to assess the specificity of MAPKAPK5 and MAP2K4 to eventual conversion to AD.

  16. Plasma protein biomarkers of Alzheimer's disease endophenotypes in asymptomatic older twins: early cognitive decline and regional brain volumes

    PubMed Central

    Kiddle, S J; Steves, C J; Mehta, M; Simmons, A; Xu, X; Newhouse, S; Sattlecker, M; Ashton, N J; Bazenet, C; Killick, R; Adnan, J; Westman, E; Nelson, S; Soininen, H; Kloszewska, I; Mecocci, P; Tsolaki, M; Vellas, B; Curtis, C; Breen, G; Williams, S C R; Lovestone, S; Spector, T D; Dobson, R J B

    2015-01-01

    There is great interest in blood-based markers of Alzheimer's disease (AD), especially in its pre-symptomatic stages. Therefore, we aimed to identify plasma proteins whose levels associate with potential markers of pre-symptomatic AD. We also aimed to characterise confounding by genetics and the effect of genetics on blood proteins in general. Panel-based proteomics was performed using SOMAscan on plasma samples from TwinsUK subjects who are asymptomatic for AD, measuring the level of 1129 proteins. Protein levels were compared with 10-year change in CANTAB-paired associates learning (PAL; n=195), and regional brain volumes (n=34). Replication of proteins associated with regional brain volumes was performed in 254 individuals from the AddNeuroMed cohort. Across all the proteins measured, genetic factors were found to explain ~26% of the variability in blood protein levels on average. The plasma level of the mitogen-activated protein kinase (MAPK) MAPKAPK5 protein was found to positively associate with the 10-year change in CANTAB-PAL in both the individual and twin difference context. The plasma level of protein MAP2K4 was found to suggestively associate negatively (Q<0.1) with the volume of the left entorhinal cortex. Future studies will be needed to assess the specificity of MAPKAPK5 and MAP2K4 to eventual conversion to AD. PMID:26080319

  17. Brain Serotonergic and Noradrenergic Deficiencies in Behavioral Variant Frontotemporal Dementia Compared to Early-Onset Alzheimer's Disease.

    PubMed

    Vermeiren, Yannick; Janssens, Jana; Aerts, Tony; Martin, Jean-Jacques; Sieben, Anne; Van Dam, Debby; De Deyn, Peter P

    2016-06-15

    Routinely prescribed psychoactive drugs in behavioral variant frontotemporal dementia (FTD) for improvement of (non)cognitive symptoms are primarily based on monoamine replacement or augmentation strategies. These were, however, initially intended to symptomatically treat other degenerative, behavioral, or personality disorders, and thus lack disease specificity. Moreover, current knowledge on brain monoaminergic neurotransmitter deficiencies in this presenile disorder is scarce, particularly with reference to changes in Alzheimer's disease (AD). The latter hence favors neurochemical comparison studies in order to elucidate the monoaminergic underpinnings of FTD compared to early-onset AD, which may contribute to better pharmacotherapy. Therefore, frozen brain samples, i.e., Brodmann area (BA) 6/8/9/10/11/12/22/24/46, amygdala, and hippocampus, of 10 neuropathologically confirmed FTD, AD, and control subjects were analyzed by means of reversed-phase high-performance liquid chromatography. Levels of serotonergic, dopaminergic, and noradrenergic compounds were measured. In nine brain areas, serotonin (5-HT) concentrations were significantly increased in FTD compared to AD patients, while 5-hydroxyindoleacetic acid/5-HT ratios were decreased in eight regions, also compared to controls. Furthermore, in all regions, noradrenaline (NA) levels were significantly higher, and 3-methoxy-4-hydroxyphenylglycol/NA ratios were significantly lower in FTD than in AD and controls. Contrarily, significantly higher dopamine (DA) levels and reduced homovanillic acid/DA ratios were only found in BA12 and BA46. Results indicate that FTD is defined by distinct serotonergic and noradrenergic deficiencies. Additional research regarding the interactions between both monoaminergic networks is required. Similarly, clinical trials investigating the effects of 5-HT1A receptor antagonists or NA-modulating agents, such as α1/2/β1-blockers, seem to have a rationale and should be considered. PMID

  18. The Influence of AD Family History and APOE4 on Mesial Temporal Lobe Activation

    PubMed Central

    Johnson, Sterling C.; Schmitz, Taylor W.; Trivedi, Mehul A.; Ries, Michele L.; Torgerson, Britta M.; Carlsson, Cynthia; Asthana, Sanjay; Hermann, Bruce P.; Sager, Mark A.

    2009-01-01

    First-degree family history of sporadic Alzheimer Disease (AD) and the apolipoprotein E ε4 (APOE4) are risk factors for developing AD. Although the role of APOE4 in AD pathogenesis has been well studied, family history remains a rarely studied and poorly understood risk factor. Both putatively cause early brain changes prior to symptomatic disease, but the relative contribution of each on brain function is unknown. We examined 68 middle-aged participants with a parent diagnosed with AD (+FH) and 64 age- and education-matched controls without a first-degree family history of any dementia (−FH). All underwent cognitive testing, APOE genotyping and a functional MRI (fMRI) encoding task that required discrimination of novel items from previously learned items. A 2 × 2 factorial ANOVA (presence/absence of parental family history and presence/absence of the APOE4) was used to detect group effects. A greater response to novel items was detected in the mesial temporal lobe and fusiform gyrus bilaterally among persons without a first-degree family history of AD. In hippocampal areas, the −FH +ε4 group exhibited the greatest signal change, and the +FH +ε4 group the least. These findings indicate that FH of AD is an important predictor of hippocampal activation during encoding and that FH may modulate the effect of APOE4 in these middle-aged adults, suggesting that an as yet unspecified factor embodied in first-degree family history of AD is influencing the expression of APOE4 on brain function. PMID:16738250

  19. Linking Brain Research to Art.

    ERIC Educational Resources Information Center

    Rettig, Perry R.; Rettig, Janet L.

    1999-01-01

    Reviews recent brain research in education. Provides five implications for teaching in art: (1) use emotion; (2) use different sense; (3) promote student self-direction; (4) enable social learning; and (5) encourage pattern finding. Describes two sample art units demonstrating how the five implications and art instruction can be integrated. (CMK)

  20. Elevating sampling

    PubMed Central

    Labuz, Joseph M.; Takayama, Shuichi

    2014-01-01

    Sampling – the process of collecting, preparing, and introducing an appropriate volume element (voxel) into a system – is often under appreciated and pushed behind the scenes in lab-on-a-chip research. What often stands in the way between proof-of-principle demonstrations of potentially exciting technology and its broader dissemination and actual use, however, is the effectiveness of sample collection and preparation. The power of micro- and nanofluidics to improve reactions, sensing, separation, and cell culture cannot be accessed if sampling is not equally efficient and reliable. This perspective will highlight recent successes as well as assess current challenges and opportunities in this area. PMID:24781100

  1. The Association Between Retinal Neuronal Layer and Brain Structure is Disrupted in Patients with Cognitive Impairment and Alzheimer's Disease.

    PubMed

    Liu, Siwei; Ong, Yi-Ting; Hilal, Saima; Loke, Yng Miin; Wong, Tien Y; Chen, Christopher Li-Hsian; Cheung, Carol Y; Zhou, Juan

    2016-09-01

    Both healthy and pathological aging due to Alzheimer's disease (AD) are associated with decreased brain grey matter volume (GMV) and disrupted white matter (WM) microstructure. Thinner macular ganglion cell-inner plexiform layer (GC-IPL) measured by spectral-domain optical coherence tomography has been reported in patients with AD and mild cognitive impairment. Emerging evidence suggested a link between thinner GC-IPL and lower GMV in subjects with no dementia using region-of-interest-based approach. However, it remains unknown whether GC-IPL thickness is associated with brain WM microstructure and how such association differed between normal and cognitively impaired subjects. Here, for subjects with no cognitive impairment (NCI), thinner GC-IPL was associated with lower WM microstructure integrity in the superior longitudinal fasciculus, inferior fronto-occipital fasciculus, corticospinal tracts, anterior thalamic radiation, and cingulum regions, while it was weakly associated with lower GMV in visual cortex and cerebellum. Nevertheless, these retina-brain associations were disrupted in the presence of cognitive impairment. Correlations between GMV and GC-IPL were lost in patients with cognitive impairment but no dementia (CIND) and AD patients. GC-IPL was related to WM microstructural disruption in similar regions with decreased significance. In contrast, lower WM microstructure integrity in the fornix showed a trend of correlation with thinner GC-IPL in both CIND and AD but not NCI. Collectively, our findings suggest the possible physiological retina-brain relationship in healthy aging, which might be disrupted by disease-induced changes in patients with cognitive impairment. Longitudinal study with larger patient sample should follow to confirm the disease mechanism behind these retina-brain relationship changes. PMID:27567815

  2. Kaon Decays from AdS/QCD

    SciTech Connect

    Schvellinger, Martin

    2008-07-28

    We briefly review one of the current applications of the AdS/CFT correspondence known as AdS/QCD and discuss about the calculation of four-point quark-flavour current correlation functions and their applications to the calculation of observables related to neutral kaon decays and neutral kaon mixing processes.

  3. An improved AFS phase for AdS3 string integrability

    NASA Astrophysics Data System (ADS)

    Abbott, Michael C.; Aniceto, Inês

    2015-04-01

    We propose a number of modifications to the classical term in the dressing phase for integrable strings in AdS3 ×S3 ×S3 ×S1, and check these against existing perturbative calculations, crossing symmetry, and the semiclassical limit of the Bethe equations. The principal change is that the phase for different masses should start with a term Q1Q2, like the one-loop AdS3 dressing phase, rather than Q2Q3 as for the original AdS5 AFS phase.

  4. On circular strings in (AdS3 × S 3)ϰ

    NASA Astrophysics Data System (ADS)

    Banerjee, Aritra; Panigrahi, Kamal L.

    2016-09-01

    The so called one-parameter (often called ϰ) deformed AdS string sigma models have attracted a lot of attention lately in the study of integrability in string theory. We construct various circular string solutions in the (AdS3 × S 3) ϰ background and describe the characteristics of such solutions qualitatively. We study the Bohr-Sommerfeld like quantization for these string states to characterise the motion. Further we find a `long' string limit of such circular strings in the ϰ-deformed AdS3 and find a novel dependence of the oscillation number on the energy in the next to leading order expansion.

  5. SAMPLING SYSTEM

    DOEpatents

    Hannaford, B.A.; Rosenberg, R.; Segaser, C.L.; Terry, C.L.

    1961-01-17

    An apparatus is given for the batch sampling of radioactive liquids such as slurries from a system by remote control, while providing shielding for protection of operating personnel from the harmful effects of radiation.

  6. The eleven observations of comets between 687 AD and 1114 AD recorded in the Anglo Saxon Chronicle

    NASA Technical Reports Server (NTRS)

    Mardon, E. G.; Williams, J.; Mardon, A. A.

    1992-01-01

    This research paper is an examination of the eleven cometary references (679AD, 729AD, 892AD, 950AD, 975AD, 995AD, 1066AD, 1097AD, 1106AD, 1110AD and 1114AD) found in the various manuscripts of The Anglo Saxon Chronicle between 678 AD and 1114 AD. The manuscripts contain more than 35 celestial observations. This is an examination of astronomical phenomena and other climatic or natural events, that are described in The Anglo Saxon Chronicle, which is also referred to as The Old English Annals.

  7. Multi-Shell Hybrid Diffusion Imaging (HYDI) at 7 Tesla in TgF344-AD Transgenic Alzheimer Rats

    PubMed Central

    Daianu, Madelaine; Jacobs, Russell E.; Weitz, Tara M.; Town, Terrence C.; Thompson, Paul M.

    2015-01-01

    Diffusion weighted imaging (DWI) is widely used to study microstructural characteristics of the brain. Diffusion tensor imaging (DTI) and high-angular resolution imaging (HARDI) are frequently used in radiology and neuroscience research but can be limited in describing the signal behavior in composite nerve fiber structures. Here, we developed and assessed the benefit of a comprehensive diffusion encoding scheme, known as hybrid diffusion imaging (HYDI), composed of 300 DWI volumes acquired at 7-Tesla with diffusion weightings at b = 1000, 3000, 4000, 8000 and 12000 s/mm2 and applied it in transgenic Alzheimer rats (line TgF344-AD) that model the full clinico-pathological spectrum of the human disease. We studied and visualized the effects of the multiple concentric “shells” when computing three distinct anisotropy maps–fractional anisotropy (FA), generalized fractional anisotropy (GFA) and normalized quantitative anisotropy (NQA). We tested the added value of the multi-shell q-space sampling scheme, when reconstructing neural pathways using mathematical frameworks from DTI and q-ball imaging (QBI). We show a range of properties of HYDI, including lower apparent anisotropy when using high b-value shells in DTI-based reconstructions, and increases in apparent anisotropy in QBI-based reconstructions. Regardless of the reconstruction scheme, HYDI improves FA-, GFA- and NQA-aided tractography. HYDI may be valuable in human connectome projects and clinical research, as well as magnetic resonance research in experimental animals. PMID:26683657

  8. High resolution A/D conversion based on piecewise conversion at lower resolution

    DOEpatents

    Terwilliger, Steve

    2012-06-05

    Piecewise conversion of an analog input signal is performed utilizing a plurality of relatively lower bit resolution A/D conversions. The results of this piecewise conversion are interpreted to achieve a relatively higher bit resolution A/D conversion without sampling frequency penalty.

  9. Investigating the Impact of Concept Mapping Software on Greek Students with Attention Deficit (AD)

    ERIC Educational Resources Information Center

    Riga, Asimina; Papayiannis, Nikolaos

    2015-01-01

    The present study investigates if there is a positive effect of the use of concept mapping software on students with Attention Deficit (AD) when learning descriptive writing in the secondary level of education. It also examines what kind of difficulties AD students may have come across during this learning procedure. Sample students were selected…

  10. Self-Regulation of Emotion, Functional Impairment, and Comorbidity among Children with AD/HD

    ERIC Educational Resources Information Center

    Anastopoulos, Arthur D.; Smith, Taylor F.; Garrett, Melanie E.; Morrissey-Kane, Erin; Schatz, Nicole K.; Sommer, Jennifer L.; Kollins, Scott H.; Ashley-Koch, Allison

    2011-01-01

    Objective: This study investigated the role of self-regulation of emotion in relation to functional impairment and comorbidity among children with and without AD/HD. Method: A total of 358 probands and their siblings participated in the study, with 74% of the sample participants affected by AD/HD. Parent-rated levels of emotional lability served…

  11. Inflation in AdS/CFT

    SciTech Connect

    Freivogel, Ben; Hubeny, Veronika E.; Maloney, Alexander; Myers, Rob; Rangamani, Mukund; Shenker, Stephen; /Stanford U., Phys. Dept.

    2005-10-07

    We study the realization of inflation within the AdS/CFT correspondence. We assume the existence of a string landscape containing at least one stable AdS vacuum and a (nearby) metastable de Sitter state. Standard arguments imply that the bulk physics in the vicinity of the AdS minimum is described by a boundary CFT. We argue that large enough bubbles of the dS phase, including those able to inflate, are described by mixed states in the CFT. Inflating degrees of freedom are traced over and do not appear explicitly in the boundary description. They nevertheless leave a distinct imprint on the mixed state. Analytic continuation allows us, in principle, to recover a large amount of nonperturbatively defined information about the inflating regime. Our work also shows that no scattering process can create an inflating region, even by quantum tunneling, since a pure state can never evolve into a mixed state under unitary evolution.We study the realization of inflation within the AdS/CFT correspondence. We assume the existence of a string landscape containing at least one stable AdS vacuum and a (nearby) metastable de Sitter state. Standard arguments imply that the bulk physics in the vicinity of the AdS minimum is described by a boundary CFT. We argue that large enough bubbles of the dS phase, including those able to inflate, are described by mixed states in the CFT. Inflating degrees of freedom are traced over and do not appear explicitly in the boundary description. They nevertheless leave a distinct imprint on the mixed state. Analytic continuation allows us, in principle, to recover a large amount of nonperturbatively defined information about the inflating regime. Our work also shows that no scattering process can create an inflating region, even by quantum tunneling, since a pure state can never evolve into a mixed state under unitary evolution.

  12. Mapping the Alzheimer’s Brain with Connectomics

    PubMed Central

    Xie, Teng; He, Yong

    2012-01-01

    Alzheimer’s disease (AD) is the most common form of dementia. As an incurable, progressive, and neurodegenerative disease, it causes cognitive and memory deficits. However, the biological mechanisms underlying the disease are not thoroughly understood. In recent years, non-invasive neuroimaging and neurophysiological techniques [e.g., structural magnetic resonance imaging (MRI), diffusion MRI, functional MRI, and EEG/MEG] and graph theory based network analysis have provided a new perspective on structural and functional connectivity patterns of the human brain (i.e., the human connectome) in health and disease. Using these powerful approaches, several recent studies of patients with AD exhibited abnormal topological organization in both global and regional properties of neuronal networks, indicating that AD not only affects specific brain regions, but also alters the structural and functional associations between distinct brain regions. Specifically, disruptive organization in the whole-brain networks in AD is involved in the loss of small-world characters and the re-organization of hub distributions. These aberrant neuronal connectivity patterns were associated with cognitive deficits in patients with AD, even with genetic factors in healthy aging. These studies provide empirical evidence to support the existence of an aberrant connectome of AD. In this review we will summarize recent advances discovered in large-scale brain network studies of AD, mainly focusing on graph theoretical analysis of brain connectivity abnormalities. These studies provide novel insights into the pathophysiological mechanisms of AD and could be helpful in developing imaging biomarkers for disease diagnosis and monitoring. PMID:22291664

  13. Superradiance instability of small rotating AdS black holes in arbitrary dimensions

    NASA Astrophysics Data System (ADS)

    Delice, Ã.-zgür; Durǧut, Türküler

    2015-07-01

    We investigate the stability of D dimensional singly rotating Myers-Perry-AdS black holes under superradiance against scalar field perturbations. It is well known that small four dimensional rotating or charged Anti-de Sitter (AdS) black holes are unstable against superradiance instability of a scalar field. Recent works extended the existence of this instability to five dimensional rotating charged AdS black holes or static charged AdS black holes in arbitrary dimensions. In this paper we analytically prove that rotating small AdS black holes in arbitrary dimensions also shows superradiance instability irrespective of the value of the (positive) angular momentum quantum number. To do this we solve the Klein-Gordon equation in the slow rotation, low frequency limit. By using the asymptotic matching technique, we are able to calculate the real and imaginary parts of the correction terms to the frequency of the scalar field due to the presence of the black hole, confirming the presence of superradiance instability. We see that, unlike in the case of static AdS black holes, the analytical method is valid for rotating AdS black holes for any value of angular momentum number and spacetime dimensions. For comparison we derive the corresponding correction terms for Myers-Perry black holes in the black hole bomb formalism in the Appendix and see that the results are in agreement.

  14. Special Report: Brain Chemistry.

    ERIC Educational Resources Information Center

    Krassner, Michael B.

    1983-01-01

    Chemical actions in the brain result in cognitive, emotional, neuroendocrine, neuromuscular, and/or neurocirculatory effects. Developments in understanding brain chemistry are discussed, considering among others, neurotransmitter chemistry, neuropeptides, drugs and the brain, antidepressants, and actions of minor tranquilizers. (JN)

  15. Brain-based Learning.

    ERIC Educational Resources Information Center

    Weiss, Ruth Palombo

    2000-01-01

    Discusses brain research and how new imaging technologies allow scientists to explore how human brains process memory, emotion, attention, patterning, motivation, and context. Explains how brain research is being used to revise learning theories. (JOW)

  16. Traumatic Brain Injury

    MedlinePlus

    Traumatic brain injury (TBI) happens when a bump, blow, jolt, or other head injury causes damage to the brain. Every year, millions of people in the U.S. suffer brain injuries. More than half are bad enough that ...

  17. Brain tumor (image)

    MedlinePlus

    Brain tumors are classified depending on the exact site of the tumor, the type of tissue involved, benign ... tendencies of the tumor, and other factors. Primary brain tumors can arise from the brain cells, the meninges ( ...

  18. Traumatic Brain Injury

    MedlinePlus

    ... Center PTACs Workspaces Log-in Search for: Traumatic Brain Injury A legacy resource from NICHCY Disability Fact ... in her. Back to top What is Traumatic Brain Injury? A traumatic brain injury (TBI) is an ...

  19. That's Using Your Brain!

    ERIC Educational Resources Information Center

    Visser, Dana R.

    1996-01-01

    Discusses new adult learning theories, including those of Roger Sperry (left brain/right brain), Paul McLean (triune brain), and Howard Gardner (multiple intelligences). Relates adult learning theory to training. (JOW)

  20. Noise-induced sensitization of human brain

    NASA Astrophysics Data System (ADS)

    Yamamoto, Yoshiharu; Hidaka, Ichiro; Nozaki, Daichi; Iso-o, Noriko; Soma, Rika; Kwak, Shin

    2002-11-01

    In the past decade, it has been recognized that noise can enhance the response of nonlinear systems to weak signals, via a mechanism known as stochastic resonance (SR). Particularly, the concept of SR has generated considerable interest in sensory biology, because it has been shown in several experimental studies that noise can assist neural systems in detecting weak signals which could not be detected in its absence. Recently, we have shown a similar type of noise-induced sensitization of human brain; externally added noise to the brain stem baroreflex centers sensitized their responses in maintaining adequate blood perfusion to the brain itself. Furthermore, the addition of noise has also shown to be useful in compensating for dysfunctions of the baroreflex centers in certain neurological diseases. It is concluded that the statistical physics concept of SR could be useful in sensitizing human brain in health and disease.

  1. Amyloid-β Precursor Protein Modulates the Sorting of Testican-1 and Contributes to Its Accumulation in Brain Tissue and Cerebrospinal Fluid from Patients with Alzheimer Disease

    PubMed Central

    Barrera-Ocampo, Alvaro; Arlt, Sönke; Matschke, Jakob; Hartmann, Ursula; Puig, Berta; Ferrer, Isidre; Zürbig, Petra; Glatzel, Markus; Jahn, Holger

    2016-01-01

    The mechanisms leading to amyloid-β (Aβ) accumulation in sporadic Alzheimer disease (AD) are unknown but both increased production or impaired clearance likely contribute to aggregation. To understand the potential roles of the extracellular matrix proteoglycan Testican-1 in the pathophysiology of AD, we used samples from AD patients and controls and an in vitro approach. Protein expression analysis showed increased levels of Testican-1 in frontal and temporal cortex of AD patients; histological analysis showed that Testican-1 accumulates and co-aggregates with Aβ plaques in the frontal, temporal and entorhinal cortices of AD patients. Proteomic analysis identified 10 fragments of Testican-1 in cerebrospinal fluid (CSF) from AD patients. HEK293T cells expressing human wild type or mutant Aβ precursor protein (APP) were transfected with Testican-1. The co-expression of both proteins modified the sorting of Testican-1 into the endocytic pathway leading to its transient accumulation in Golgi, which seemed to affect APP processing, as indicated by reduced Aβ40 and Aβ42 levels in APP mutant cells. In conclusion, patient data reflect a clearance impairment that may favor Aβ accumulation in AD brains and our in vitro model supports the notion that the interaction between APP and Testican-1 may be a key step in the production and aggregation of Aβ species. PMID:27486134

  2. Amyloid-β Precursor Protein Modulates the Sorting of Testican-1 and Contributes to Its Accumulation in Brain Tissue and Cerebrospinal Fluid from Patients with Alzheimer Disease.

    PubMed

    Barrera-Ocampo, Alvaro; Arlt, Sönke; Matschke, Jakob; Hartmann, Ursula; Puig, Berta; Ferrer, Isidre; Zürbig, Petra; Glatzel, Markus; Sepulveda-Falla, Diego; Jahn, Holger

    2016-09-01

    The mechanisms leading to amyloid-β (Aβ) accumulation in sporadic Alzheimer disease (AD) are unknown but both increased production or impaired clearance likely contribute to aggregation. To understand the potential roles of the extracellular matrix proteoglycan Testican-1 in the pathophysiology of AD, we used samples from AD patients and controls and an in vitro approach. Protein expression analysis showed increased levels of Testican-1 in frontal and temporal cortex of AD patients; histological analysis showed that Testican-1 accumulates and co-aggregates with Aβ plaques in the frontal, temporal and entorhinal cortices of AD patients. Proteomic analysis identified 10 fragments of Testican-1 in cerebrospinal fluid (CSF) from AD patients. HEK293T cells expressing human wild type or mutant Aβ precursor protein (APP) were transfected with Testican-1. The co-expression of both proteins modified the sorting of Testican-1 into the endocytic pathway leading to its transient accumulation in Golgi, which seemed to affect APP processing, as indicated by reduced Aβ40 and Aβ42 levels in APP mutant cells. In conclusion, patient data reflect a clearance impairment that may favor Aβ accumulation in AD brains and our in vitro model supports the notion that the interaction between APP and Testican-1 may be a key step in the production and aggregation of Aβ species. PMID:27486134

  3. BrainAGE in Mild Cognitive Impaired Patients: Predicting the Conversion to Alzheimer’s Disease

    PubMed Central

    Klöppel, Stefan; Koutsouleris, Nikolaos; Sauer, Heinrich

    2013-01-01

    Alzheimer’s disease (AD), the most common form of dementia, shares many aspects of abnormal brain aging. We present a novel magnetic resonance imaging (MRI)-based biomarker that predicts the individual progression of mild cognitive impairment (MCI) to AD on the basis of pathological brain aging patterns. By employing kernel regression methods, the expression of normal brain-aging patterns forms the basis to estimate the brain age of a given new subject. If the estimated age is higher than the chronological age, a positive brain age gap estimation (BrainAGE) score indicates accelerated atrophy and is considered a risk factor for conversion to AD. Here, the BrainAGE framework was applied to predict the individual brain ages of 195 subjects with MCI at baseline, of which a total of 133 developed AD during 36 months of follow-up (corresponding to a pre-test probability of 68%). The ability of the BrainAGE framework to correctly identify MCI-converters was compared with the performance of commonly used cognitive scales, hippocampus volume, and state-of-the-art biomarkers derived from cerebrospinal fluid (CSF). With accuracy rates of up to 81%, BrainAGE outperformed all cognitive scales and CSF biomarkers in predicting conversion of MCI to AD within 3 years of follow-up. Each additional year in the BrainAGE score was associated with a 10% greater risk of developing AD (hazard rate: 1.10 [CI: 1.07–1.13]). Furthermore, the post-test probability was increased to 90% when using baseline BrainAGE scores to predict conversion to AD. The presented framework allows an accurate prediction even with multicenter data. Its fast and fully automated nature facilitates the integration into the clinical workflow. It can be exploited as a tool for screening as well as for monitoring treatment options. PMID:23826273

  4. No-carrier-added (/sup 18/F)-N-methylspiroperidol

    DOEpatents

    Shiue, C.Y.; Fowler, J.S.; Wolf, A.P.

    1985-10-04

    The present invention is directed to the synthesis of a radioligand, labeled with a positron emitting radionuclide which is suitable for dynamic studies in humans using positron emission transaxial tomography. No-carrier-added (NCA) (/sup 18/F)-N-methylspiroperiodl is prepared from four different sustrates: p-nitrobenzonitrile, cyclopropyl p-nitrophenyl ketone, p-cyclopropanoyl-N,N,N-trimethylanilinium iodide and p-cyclopropanoyl-N,N,N-trimethylanilinium perchlorate. The process for the production of NCA (/sup 18/F)-N-methylspiroperidol is a nucleophilic aromatic substitution reaction. Furthermore, the compound of this invention is shown to be effective as a new drug of choice for in vivo examination of dopamine binding sites in a human brain. In particular, this drug is primarily useful in the noninvasive technique of positron emission transaxial tomography (PETT).

  5. Supergravity background of the λ-deformed AdS3 × S3 supercoset

    NASA Astrophysics Data System (ADS)

    Chervonyi, Yuri; Lunin, Oleg

    2016-09-01

    We construct the solution of type IIB supergravity describing the integrable λ-deformation of the AdS3 ×S3 supercoset. While the geometry corresponding to the deformation of the bosonic coset has been found in the past, our background is more natural for studying superstrings, and several interesting features distinguish our solution from its bosonic counterpart. We also report progress towards constructing the λ-deformation of the AdS5 ×S5 supercoset.

  6. SAMPLING OSCILLOSCOPE

    DOEpatents

    Sugarman, R.M.

    1960-08-30

    An oscilloscope is designed for displaying transient signal waveforms having random time and amplitude distributions. The oscilloscopc is a sampling device that selects for display a portion of only those waveforms having a particular range of amplitudes. For this purpose a pulse-height analyzer is provided to screen the pulses. A variable voltage-level shifter and a time-scale rampvoltage generator take the pulse height relative to the start of the waveform. The variable voltage shifter produces a voltage level raised one step for each sequential signal waveform to be sampled and this results in an unsmeared record of input signal waveforms. Appropriate delay devices permit each sample waveform to pass its peak amplitude before the circuit selects it for display.

  7. Sampling apparatus

    DOEpatents

    Gordon, Norman R.; King, Lloyd L.; Jackson, Peter O.; Zulich, Alan W.

    1989-01-01

    A sampling apparatus is provided for sampling substances from solid surfaces. The apparatus includes first and second elongated tubular bodies which telescopically and sealingly join relative to one another. An absorbent pad is mounted to the end of a rod which is slidably received through a passageway in the end of one of the joined bodies. The rod is preferably slidably and rotatably received through the passageway, yet provides a selective fluid tight seal relative thereto. A recess is formed in the rod. When the recess and passageway are positioned to be coincident, fluid is permitted to flow through the passageway and around the rod. The pad is preferably laterally orientable relative to the rod and foldably retractable to within one of the bodies. A solvent is provided for wetting of the pad and solubilizing or suspending the material being sampled from a particular surface.

  8. Sampling apparatus

    DOEpatents

    Gordon, N.R.; King, L.L.; Jackson, P.O.; Zulich, A.W.

    1989-07-18

    A sampling apparatus is provided for sampling substances from solid surfaces. The apparatus includes first and second elongated tubular bodies which telescopically and sealingly join relative to one another. An absorbent pad is mounted to the end of a rod which is slidably received through a passageway in the end of one of the joined bodies. The rod is preferably slidably and rotatably received through the passageway, yet provides a selective fluid tight seal relative thereto. A recess is formed in the rod. When the recess and passageway are positioned to be coincident, fluid is permitted to flow through the passageway and around the rod. The pad is preferably laterally orientable relative to the rod and foldably retractable to within one of the bodies. A solvent is provided for wetting of the pad and solubilizing or suspending the material being sampled from a particular surface. 15 figs.

  9. Studies on the ADS/CFT correspondence

    NASA Astrophysics Data System (ADS)

    Muck, Wolfgang

    1999-11-01

    This thesis summarizes original research on the topic of the ``AdS/CFT correspondence.'' This correspondence, which was first conjectured by Maldacena [ Adv. Theor. Math. Phys. 2, 231 (1998)] and subsequently formulated by Gubser, Klebanov and Polyakov [Phys. Lett. B 428, 105 (1998) and by Witten [Adv. Theor. Math. Phys. 2, 253 (1998)], relates field theories on (d + 1)-dimensional anti-de Sitter (AdS) spaces and conformal field theories (CFTs) in d dimensions with each other. Its main prediction is that the correlation functions of certain quantum CFTs are determined by the dynamics of classical field theories on AdS spaces. Starting from a correspondence formula provided by the authors above, several CFT correlation functions are calculated and agreement with the forms dictated by conformal invariance is found. The necessary renormalization is carried out in the ``ɛ- prescription.'' Details of renormalization and the breaking of conformal symmetries in special cases are investigated by means of the example of the scalar field. The ``asymptotic prescription'' is used to prove a suggestion by Klebanov and Witten [hep- th/9905104] about the treatment of irregular boundary conditions valid to all orders of perturbation theory. The treatment of AdS gravity, which enables the calculation of correlation functions of CFT energy momentum tensors, is carried out in the time slicing formalism. The calculated two-point functions and Weyl anomalies agree with results known from pure CFT considerations. The Wess Zumino model on AdS4 is discussed as an example containing supersymmetry. It is shown that the model yields the correlation functions of conformal fields belonging to a d = 3, N = 1 superconformal multiplet.

  10. Corpora Amylacea of Brain Tissue from Neurodegenerative Diseases Are Stained with Specific Antifungal Antibodies

    PubMed Central

    Pisa, Diana; Alonso, Ruth; Rábano, Alberto; Carrasco, Luis

    2016-01-01

    The origin and potential function of corpora amylacea (CA) remains largely unknown. Low numbers of CA are detected in the aging brain of normal individuals but they are abundant in the central nervous system of patients with neurodegenerative diseases. In the present study, we show that CA from patients diagnosed with Alzheimer's disease (AD) contain fungal proteins as detected by immunohistochemistry analyses. Accordingly, CA were labeled with different anti-fungal antibodies at the external surface, whereas the central portion composed of calcium salts contain less proteins. Detection of fungal proteins was achieved using a number of antibodies raised against different fungal species, which indicated cross-reactivity between the fungal proteins present in CA and the antibodies employed. Importantly, these antibodies do not immunoreact with cellular proteins. Additionally, CNS samples from patients diagnosed with amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD) also contained CA that were immunoreactive with a range of antifungal antibodies. However, CA were less abundant in ALS or PD patients as compared to CNS samples from AD. By contrast, CA from brain tissue of control subjects were almost devoid of fungal immunoreactivity. These observations are consistent with the concept that CA associate with fungal infections and may contribute to the elucidation of the origin of CA. PMID:27013948

  11. Corpora Amylacea of Brain Tissue from Neurodegenerative Diseases Are Stained with Specific Antifungal Antibodies.

    PubMed

    Pisa, Diana; Alonso, Ruth; Rábano, Alberto; Carrasco, Luis

    2016-01-01

    The origin and potential function of corpora amylacea (CA) remains largely unknown. Low numbers of CA are detected in the aging brain of normal individuals but they are abundant in the central nervous system of patients with neurodegenerative diseases. In the present study, we show that CA from patients diagnosed with Alzheimer's disease (AD) contain fungal proteins as detected by immunohistochemistry analyses. Accordingly, CA were labeled with different anti-fungal antibodies at the external surface, whereas the central portion composed of calcium salts contain less proteins. Detection of fungal proteins was achieved using a number of antibodies raised against different fungal species, which indicated cross-reactivity between the fungal proteins present in CA and the antibodies employed. Importantly, these antibodies do not immunoreact with cellular proteins. Additionally, CNS samples from patients diagnosed with amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD) also contained CA that were immunoreactive with a range of antifungal antibodies. However, CA were less abundant in ALS or PD patients as compared to CNS samples from AD. By contrast, CA from brain tissue of control subjects were almost devoid of fungal immunoreactivity. These observations are consistent with the concept that CA associate with fungal infections and may contribute to the elucidation of the origin of CA. PMID:27013948

  12. Unsupervised brain segmentation using T2 window

    NASA Astrophysics Data System (ADS)

    Alyassin, Abdal M.; Cline, Harvey E.

    2002-05-01

    Measurement of brain structures could lead to important diagnostic information and could indicate the success or failure of a certain pharmaceutical drug. We have developed a totally unsupervised technique that segments and quantifies brain structures from T2 dual echo MR images. The technique classified four different tissue clusters in a scatter plot (air, CSF, brain, and face). Several novel image-processing techniques were implemented to reduce the spread of these clusters and subsequently generate tissue based T2 windows. These T2 windows encompassed all the information needed to segment and subsequently quantify the corresponding tissues in an automatic fashion. We have applied the technique on nineteen MR data sets (16 normal and 3 Alzheimer diseased [AD] patients). The measurements from the T2 window technique differentiated AD patients from normal subjects. The mean value of the %CSF from total the brain was %29.2 higher for AD patients from the %CSF for normal subjects. Furthermore, the technique ran under 30 seconds per data set on a PC with 550 MHz dual processors.

  13. Rapid Active Sampling Package

    NASA Technical Reports Server (NTRS)

    Peters, Gregory

    2010-01-01

    A field-deployable, battery-powered Rapid Active Sampling Package (RASP), originally designed for sampling strong materials during lunar and planetary missions, shows strong utility for terrestrial geological use. The technology is proving to be simple and effective for sampling and processing materials of strength. Although this originally was intended for planetary and lunar applications, the RASP is very useful as a powered hand tool for geologists and the mining industry to quickly sample and process rocks in the field on Earth. The RASP allows geologists to surgically acquire samples of rock for later laboratory analysis. This tool, roughly the size of a wrench, allows the user to cut away swaths of weathering rinds, revealing pristine rock surfaces for observation and subsequent sampling with the same tool. RASPing deeper (.3.5 cm) exposes single rock strata in-situ. Where a geologist fs hammer can only expose unweathered layers of rock, the RASP can do the same, and then has the added ability to capture and process samples into powder with particle sizes less than 150 microns, making it easier for XRD/XRF (x-ray diffraction/x-ray fluorescence). The tool uses a rotating rasp bit (or two counter-rotating bits) that resides inside or above the catch container. The container has an open slot to allow the bit to extend outside the container and to allow cuttings to enter and be caught. When the slot and rasp bit are in contact with a substrate, the bit is plunged into it in a matter of seconds to reach pristine rock. A user in the field may sample a rock multiple times at multiple depths in minutes, instead of having to cut out huge, heavy rock samples for transport back to a lab for analysis. Because of the speed and accuracy of the RASP, hundreds of samples can be taken in one day. RASP-acquired samples are small and easily carried. A user can characterize more area in less time than by using conventional methods. The field-deployable RASP used a Ni

  14. Alzheimer's Disease Detection in Brain Magnetic Resonance Images Using Multiscale Fractal Analysis

    PubMed Central

    Lahmiri, Salim; Boukadoum, Mounir

    2013-01-01

    We present a new automated system for the detection of brain magnetic resonance images (MRI) affected by Alzheimer's disease (AD). The MRI is analyzed by means of multiscale analysis (MSA) to obtain its fractals at six different scales. The extracted fractals are used as features to differentiate healthy brain MRI from those of AD by a support vector machine (SVM) classifier. The result of classifying 93 brain MRIs consisting of 51 images of healthy brains and 42 of brains affected by AD, using leave-one-out cross-validation method, yielded 99.18% ± 0.01 classification accuracy, 100% sensitivity, and 98.20% ± 0.02 specificity. These results and a processing time of 5.64 seconds indicate that the proposed approach may be an efficient diagnostic aid for radiologists in the screening for AD. PMID:24967286

  15. Terahertz spectroscopy of brain tissue from a mouse model of Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Shi, Lingyan; Shumyatsky, Pavel; Rodríguez-Contreras, Adrián; Alfano, Robert

    2016-01-01

    The terahertz (THz) absorption and index of refraction of brain tissues from a mouse model of Alzheimer's disease (AD) and a control wild-type (normal) mouse were compared using THz time-domain spectroscopy (THz-TDS). Three dominating absorption peaks associated to torsional-vibrational modes were observed in AD tissue, at about 1.44, 1.8, and 2.114 THz, closer to the peaks of free tryptophan molecules than in normal tissue. A possible reason is that there is more free tryptophan in AD brain tissue, while in normal brain tissue more tryptophan is attached to other molecules. Our study suggests that THz-absorption modes may be used as an AD biomarker fingerprint in brain, and that THz-TDS is a promising technique for early diagnosis of AD.

  16. [Ceruloplasmin (Cp) and iron in connection with Parkinson's disease (PD) and Alzheimer's disease (AD)].

    PubMed

    Johannesson, Thorkell; Kristinsson, Jakob; Torsdottir, Gudlaug; Snaedal, Jon

    2012-10-01

    Ceruloplasmin, a multi-copper oxidase with four active copper atoms, oxidizes Fe2+ to Fe3+ and concomittantly fully reduces oxygen to water. The oxygenation of iron is a requisite for transferrin transport of iron and keeping noxious Fe2+ low. In the central nervous system (CNS) Cp is mostly localized in end feet of astrocytes surrounding capillaries and attached by a glycosylphosphatidylinositol-anchor. In aceruloplasminaemia, a rare recessive hereditary disease, complete loss of Cp is accompanied by disorders of iron metabolism and lesions in CNS and outside. In PD Cp concentration and oxidative activity in serum are significantly lowered with iron deposits and lesions in substantia nigra and basal ganglia. Changes in Cp-genes might be causative in these disorders. By inducing neuromelanin synthesis Cp may protect neurons in substantia nigra. In AD Cp activity in serum, but not concentration, is significantly lowered. Changes in Cp-genes have not been verified in AD. Total amounts of iron are not increased in AD brains although iron deposits and cortical lesions are numerous. Total copper is significantly lowered in AD brains. This may result in defective synthesis of Cp and other copper enzymes. - In conclusion, the defective Cp activity, associated with iron disorders, is seemingly of importance in PD and also in AD with other copper enzyme defects possibly involved.

  17. Brain templates and atlases.

    PubMed

    Evans, Alan C; Janke, Andrew L; Collins, D Louis; Baillet, Sylvain

    2012-08-15

    The core concept within the field of brain mapping is the use of a standardized, or "stereotaxic", 3D coordinate frame for data analysis and reporting of findings from neuroimaging experiments. This simple construct allows brain researchers to combine data from many subjects such that group-averaged signals, be they structural or functional, can be detected above the background noise that would swamp subtle signals from any single subject. Where the signal is robust enough to be detected in individuals, it allows for the exploration of inter-individual variance in the location of that signal. From a larger perspective, it provides a powerful medium for comparison and/or combination of brain mapping findings from different imaging modalities and laboratories around the world. Finally, it provides a framework for the creation of large-scale neuroimaging databases or "atlases" that capture the population mean and variance in anatomical or physiological metrics as a function of age or disease. However, while the above benefits are not in question at first order, there are a number of conceptual and practical challenges that introduce second-order incompatibilities among experimental data. Stereotaxic mapping requires two basic components: (i) the specification of the 3D stereotaxic coordinate space, and (ii) a mapping function that transforms a 3D brain image from "native" space, i.e. the coordinate frame of the scanner at data acquisition, to that stereotaxic space. The first component is usually expressed by the choice of a representative 3D MR image that serves as target "template" or atlas. The native image is re-sampled from native to stereotaxic space under the mapping function that may have few or many degrees of freedom, depending upon the experimental design. The optimal choice of atlas template and mapping function depend upon considerations of age, gender, hemispheric asymmetry, anatomical correspondence, spatial normalization methodology and disease

  18. Brain templates and atlases.

    PubMed

    Evans, Alan C; Janke, Andrew L; Collins, D Louis; Baillet, Sylvain

    2012-08-15

    The core concept within the field of brain mapping is the use of a standardized, or "stereotaxic", 3D coordinate frame for data analysis and reporting of findings from neuroimaging experiments. This simple construct allows brain researchers to combine data from many subjects such that group-averaged signals, be they structural or functional, can be detected above the background noise that would swamp subtle signals from any single subject. Where the signal is robust enough to be detected in individuals, it allows for the exploration of inter-individual variance in the location of that signal. From a larger perspective, it provides a powerful medium for comparison and/or combination of brain mapping findings from different imaging modalities and laboratories around the world. Finally, it provides a framework for the creation of large-scale neuroimaging databases or "atlases" that capture the population mean and variance in anatomical or physiological metrics as a function of age or disease. However, while the above benefits are not in question at first order, there are a number of conceptual and practical challenges that introduce second-order incompatibilities among experimental data. Stereotaxic mapping requires two basic components: (i) the specification of the 3D stereotaxic coordinate space, and (ii) a mapping function that transforms a 3D brain image from "native" space, i.e. the coordinate frame of the scanner at data acquisition, to that stereotaxic space. The first component is usually expressed by the choice of a representative 3D MR image that serves as target "template" or atlas. The native image is re-sampled from native to stereotaxic space under the mapping function that may have few or many degrees of freedom, depending upon the experimental design. The optimal choice of atlas template and mapping function depend upon considerations of age, gender, hemispheric asymmetry, anatomical correspondence, spatial normalization methodology and disease

  19. Genes Might Explain Hispanics' Added Longevity

    MedlinePlus

    ... University of California, Los Angeles. For example, the biological clock measured Hispanic women's "genetic" age as 2. ... and how long they live," he added. The biological clock used in the new study evaluates the ...

  20. Underweight Seniors May Have Added Alzheimer's Risk

    MedlinePlus

    ... fullstory_160278.html Underweight Seniors May Have Added Alzheimer's Risk Study links lower body weight to increased ... older adults' risk of the memory-robbing disorder Alzheimer's disease, new research suggests. The study included 280 ...

  1. Heat kernels on cone of AdS2 and k-wound circular Wilson loop in AdS5 × S5 superstring

    NASA Astrophysics Data System (ADS)

    Bergamin, R.; Tseytlin, A. A.

    2016-04-01

    We compute the one-loop world-sheet correction to partition function of {{AdS}}5× {{{S}}}5 superstring that should be representing k-fundamental circular Wilson loop in planar limit. The 2d metric of the minimal surface ending on k-wound circle at the boundary is that of a cone of AdS2 with deficit 2π (1-k). We compute the determinants of 2d fluctuation operators by first constructing heat kernels of scalar and spinor Laplacians on the cone using the Sommerfeld formula. The final expression for the k-dependent part of the one-loop correction has simple integral representation but is different from earlier results.

  2. Junk Food Ads Sway Kids' Preferences

    MedlinePlus

    ... Kids' Preferences Children under 8 most vulnerable to marketing's effects, study says To use the sharing features ... studies. The researchers found that ads and other marketing for products high in sugar or salt have ...

  3. Testing the AdS/CFT Correspondence

    SciTech Connect

    Klebanov, Igor R.

    2008-07-28

    This lecture begins with some history and basic facts about string theory and its connections with strong interactions. Comparisons of stacks of Dirichlet branes with curved backgrounds produced by them are used to motivate the AdS/CFT correspondence between superconformal gauge theory and string theory on a product of Anti-de Sitter space and a compact manifold. The ensuing duality between semi-classical spinning strings and long gauge theory operators is briefly reviewed. We go on to describe a recent test of the AdS/CFT correspondence using the Wilson loop cusp anomaly as a function of the coupling, which also enters dimensions of high-spin operators. Finally, strongly coupled thermal SYM theory is explored via a black hole in 5-dimensional AdS space, which leads to explicit results for its entropy and shear viscosity.

  4. Trust Based Routing in Ad Hoc Network

    NASA Astrophysics Data System (ADS)

    Talati, Mikita V.; Valiveti, Sharada; Kotecha, K.

    Ad Hoc network often termed as an infrastructure-less, self- organized or spontaneous network.The execution and survival of an ad-hoc network is solely dependent upon the cooperative and trusting nature of its nodes. However, this naive dependency on intermediate nodes makes the ad-hoc network vulnerable to passive and active attacks by malicious nodes and cause inflict severe damage. A number of protocols have been developed to secure ad-hoc networks using cryptographic schemes, but all rely on the presence of trust authority. Due to mobility of nodes and limitation of resources in wireless network one interesting research area in MANET is routing. This paper offers various trust models and trust based routing protocols to improve the trustworthiness of the neighborhood.Thus it helps in selecting the most secure and trustworthy route from the available ones for the data transfer.

  5. The Mutation SK(ad-3A) Cancels the Dominance of ad-3A+ over ad-3A in the Ascus of Neurospora

    PubMed Central

    Delange, A. M.

    1981-01-01

    A newly induced mutant of Neurospora, when crossed with an ad-3A mutant, produces asci with four viable black and four inviable white ascospores. The survivors always contain the new mutant allele, never ad-3A. The new allele, which is called SK(ad-3A) (for spore killer of ad-3A), is located at or very near the ad-3A locus.—In crosses homozygous for ad-3A, each ascus contains only inviable white ascospores. This defect in ascospore maturation is complemented by the wild-type allele, ad-3A+ (crosses heterozygous for ad-3A and ad-3A+ produce mainly viable ascospores), but it is not complemented by the new SK(ad-3A) allele (all ad-3A ascospores from crosses heterozygous for SK(ad-3A) and ad-3A are white and inviable). In crosses homozygous for SK(ad-3A) or heterozygous for SK(ad-3A) and ad-3A+, each ascus contains only viable black ascospores. SK(ad-3A) does not require adenine for growth, and forced heterokaryons between SK(ad-3A) and ad-3A grow at wild-type rates and produce conidia of both genotypes with approximately equal frequency. Thus, the action of SK(ad-3A) is apparently restricted to ascospore formation. Possible mechanisms of the action of this new allele are discussed. PMID:6456169

  6. Image Ads and Issue Ads in U.S. Presidential Advertising: Using Videostyle To Explore Stylistic Differences in Televised Political Ads From 1952 to 2000.

    ERIC Educational Resources Information Center

    Johnston, Anne; Kaid, Lynda Lee

    2002-01-01

    Explores the differences in techniques, strategies, narratives, and symbols used in 1,213 television issue ads and image ads from 13 U.S. presidential campaigns. Concludes that although the majority of both types of ads were positive, negative appeals dominated a higher percentage of issue ads as compared with image ads. (SG)

  7. Interconnection between brain and retinal neurodegenerations.

    PubMed

    Jindal, Vishal

    2015-01-01

    The eye is a special sensory organ, which is basically an extension of the brain. Both are derived from neural tube and consist of neurons. Therefore, diseases of both the brain and eye should have some similarity. Neurodegenerative disorders like Alzheimer's disease (AD) is the major cause of dementia in the world. Amyloid deposition in the cerebral cortex and hippocampal region is the basic pathology in AD. But along with it, there are various changes that take place in the eye, i.e., abnormal pupillary reaction, decreased vision, decreased contrast sensitivity, visual field changes, loss of retinal ganglionic cells and retinal fiber layer, peripapillary atrophy, increased cup-disk ratio, retinal thinning, tortuosity of blood vessels, and deposition of Aβ-like substance in the retina. And these changes are present in the early part of the disease when only mild cognitive impairment is there. As the brain is covered by a hard bony skull which makes it difficult to directly visualize the changes occurring in the brain at molecular levels, finer details of disease progression are not available with us. But the eye is the window of the brain; with advanced modern techniques, we can directly visualize the changes in the retina at a very fine level. Therefore, by depicting neurodegenerative changes in the eye, we can diagnose and manage AD at very early stages. Along with it, retinal neurodegenerations like glaucoma and age-related macular degeneration (ARMD) are the major cause of loss of vision, and still, there are no effective treatment modalities for these blinding conditions. So if we can understand its pathogenesis and progression by correlating with brain neurodegenerations, we can come up with a better therapy for glaucoma and ARMD.

  8. Interconnection between brain and retinal neurodegenerations.

    PubMed

    Jindal, Vishal

    2015-01-01

    The eye is a special sensory organ, which is basically an extension of the brain. Both are derived from neural tube and consist of neurons. Therefore, diseases of both the brain and eye should have some similarity. Neurodegenerative disorders like Alzheimer's disease (AD) is the major cause of dementia in the world. Amyloid deposition in the cerebral cortex and hippocampal region is the basic pathology in AD. But along with it, there are various changes that take place in the eye, i.e., abnormal pupillary reaction, decreased vision, decreased contrast sensitivity, visual field changes, loss of retinal ganglionic cells and retinal fiber layer, peripapillary atrophy, increased cup-disk ratio, retinal thinning, tortuosity of blood vessels, and deposition of Aβ-like substance in the retina. And these changes are present in the early part of the disease when only mild cognitive impairment is there. As the brain is covered by a hard bony skull which makes it difficult to directly visualize the changes occurring in the brain at molecular levels, finer details of disease progression are not available with us. But the eye is the window of the brain; with advanced modern techniques, we can directly visualize the changes in the retina at a very fine level. Therefore, by depicting neurodegenerative changes in the eye, we can diagnose and manage AD at very early stages. Along with it, retinal neurodegenerations like glaucoma and age-related macular degeneration (ARMD) are the major cause of loss of vision, and still, there are no effective treatment modalities for these blinding conditions. So if we can understand its pathogenesis and progression by correlating with brain neurodegenerations, we can come up with a better therapy for glaucoma and ARMD. PMID:24826919

  9. Aberrant brain stem morphometry associated with sleep disturbance in drug-naïve subjects with Alzheimer’s disease

    PubMed Central

    Lee, Ji Han; Jung, Won Sang; Choi, Woo Hee; Lim, Hyun Kook

    2016-01-01

    Objective Among patients with Alzheimer’s disease (AD), sleep disturbances are common and serious noncognitive symptoms. Previous studies of AD patients have identified deformations in the brain stem, which may play an important role in the regulation of sleep. The aim of this study was to further investigate the relationship between sleep disturbances and alterations in brain stem morphology in AD. Materials and methods In 44 patients with AD and 40 healthy elderly controls, sleep disturbances were measured using the Neuropsychiatry Inventory sleep subscale. We employed magnetic resonance imaging-based automated segmentation tools to examine the relationship between sleep disturbances and changes in brain stem morphology. Results Analyses of the data from AD subjects revealed significant correlations between the Neuropsychiatry Inventory sleep-subscale scores and structural alterations in the left posterior lateral region of the brain stem, as well as normalized brain stem volumes. In addition, significant group differences in posterior brain stem morphology were observed between the AD group and the control group. Conclusion This study is the first to analyze an association between sleep disturbances and brain stem morphology in AD. In line with previous findings, this study lends support to the possibility that brain stem structural abnormalities might be important neurobiological mechanisms underlying sleep disturbances associated with AD. Further longitudinal research is needed to confirm these findings. PMID:27601903

  10. Aberrant brain stem morphometry associated with sleep disturbance in drug-naïve subjects with Alzheimer’s disease

    PubMed Central

    Lee, Ji Han; Jung, Won Sang; Choi, Woo Hee; Lim, Hyun Kook

    2016-01-01

    Objective Among patients with Alzheimer’s disease (AD), sleep disturbances are common and serious noncognitive symptoms. Previous studies of AD patients have identified deformations in the brain stem, which may play an important role in the regulation of sleep. The aim of this study was to further investigate the relationship between sleep disturbances and alterations in brain stem morphology in AD. Materials and methods In 44 patients with AD and 40 healthy elderly controls, sleep disturbances were measured using the Neuropsychiatry Inventory sleep subscale. We employed magnetic resonance imaging-based automated segmentation tools to examine the relationship between sleep disturbances and changes in brain stem morphology. Results Analyses of the data from AD subjects revealed significant correlations between the Neuropsychiatry Inventory sleep-subscale scores and structural alterations in the left posterior lateral region of the brain stem, as well as normalized brain stem volumes. In addition, significant group differences in posterior brain stem morphology were observed between the AD group and the control group. Conclusion This study is the first to analyze an association between sleep disturbances and brain stem morphology in AD. In line with previous findings, this study lends support to the possibility that brain stem structural abnormalities might be important neurobiological mechanisms underlying sleep disturbances associated with AD. Further longitudinal research is needed to confirm these findings.

  11. Can Ketones Help Rescue Brain Fuel Supply in Later Life? Implications for Cognitive Health during Aging and the Treatment of Alzheimer's Disease.

    PubMed

    Cunnane, Stephen C; Courchesne-Loyer, Alexandre; Vandenberghe, Camille; St-Pierre, Valérie; Fortier, Mélanie; Hennebelle, Marie; Croteau, Etienne; Bocti, Christian; Fulop, Tamas; Castellano, Christian-Alexandre

    2016-01-01

    We propose that brain energy deficit is an important pre-symptomatic feature of Alzheimer's disease (AD) that requires closer attention in the development of AD therapeutics. Our rationale is fourfold: (i) Glucose uptake is lower in the frontal cortex of people >65 years-old despite cognitive scores that are normal for age. (ii) The regional deficit in brain glucose uptake is present in adults <40 years-old who have genetic or lifestyle risk factors for AD but in whom cognitive decline has not yet started. Examples include young adult carriers of presenilin-1 or apolipoprotein E4, and young adults with mild insulin resistance or with a maternal family history of AD. (iii) Regional brain glucose uptake is impaired in AD and mild cognitive impairment (MCI), but brain uptake of ketones (beta-hydroxybutyrate and acetoacetate), remains the same in AD and MCI as in cognitively healthy age-matched controls. These observations point to a brain fuel deficit which appears to be specific to glucose, precedes cognitive decline associated with AD, and becomes more severe as MCI progresses toward AD. Since glucose is the brain's main fuel, we suggest that gradual brain glucose exhaustion is contributing significantly to the onset or progression of AD. (iv) Interventions that raise ketone availability to the brain improve cognitive outcomes in both MCI and AD as well as in acute experimental hypoglycemia. Ketones are the brain's main alternative fuel to glucose and brain ketone uptake is still normal in MCI and in early AD, which would help explain why ketogenic interventions improve some cognitive outcomes in MCI and AD. We suggest that the brain energy deficit needs to be overcome in order to successfully develop more effective therapeutics for AD. At present, oral ketogenic supplements are the most promising means of achieving this goal. PMID:27458340

  12. Comment on the scaling function in AdS4 × Bbb CBbb P3

    NASA Astrophysics Data System (ADS)

    Gromov, Nikolay; Mikhaylov, Victor

    2009-04-01

    The folded spinning string in AdS3 gives us an important insight into AdS/CFT duality. Recently its one-loop energy was analyzed in the context of AdS4/CFT3 by McLoughlin and Roiban arXiv:0807.3965, by Alday, Arutyunov and Bykov arXiv:0807.4400 and by Krishnan arXiv:0807.4561. They computed the spectrum of the fluctuations around the classical solution. In this paper we reproduce their results using the algebraic curve technique and show that under some natural resummation of the fluctuation energies the one-loop energy agrees perfectly with the predictions of arXiv:0807.0777. This provides a further support of the all-loop Bethe equations and of the AdS4 × Bbb CBbb P3 algebraic curve developed in arXiv:0807.0437.

  13. AdS5×S(5) mirror model as a string sigma model.

    PubMed

    Arutyunov, Gleb; van Tongeren, Stijn J

    2014-12-31

    Doing a double Wick rotation in the world sheet theory of the light cone AdS5×S(5) superstring results in an inequivalent, so-called mirror theory that plays a central role in the field of integrability in the AdS-CFT correspondence. We show that this mirror theory can be interpreted as the light cone theory of a free string on a different background. This background is related to dS5×H(5) by a double T-duality, and has hidden supersymmetry. The geometry can also be extracted from an integrable deformation of the AdS5×S(5) sigma model, and we prove the observed mirror duality of these deformed models at the bosonic level as a byproduct. While we focus on AdS5×S(5), our results apply more generally. PMID:25615306

  14. Supersymmetric black holes in AdS4 from very special geometry

    NASA Astrophysics Data System (ADS)

    Gnecchi, Alessandra; Halmagyi, Nick

    2014-04-01

    Supersymmetric black holes in AdS spacetime are inherently interesting for the AdS/CFT correspondence. Within a four dimensional gauged supergravity theory coupled to vector multiplets, the only analytic solutions for regular, supersymmetric, static black holes in AdS4 are those in the STU-model due to Cacciatori and Klemm. We study a class of U (1)-gauged supergravity theories coupled to vector multiplets which have a cubic prepotential, the scalar manifold is then a very special Kähler manifold. When the resulting very special Kähler manifold is a homogeneous space, we find analytic solutions for static, supersymmetric AdS4 black holes with vanishing axions. The horizon geometries of our solutions are constant curvature Riemann surfaces of arbitrary genus.

  15. AdS5×S(5) mirror model as a string sigma model.

    PubMed

    Arutyunov, Gleb; van Tongeren, Stijn J

    2014-12-31

    Doing a double Wick rotation in the world sheet theory of the light cone AdS5×S(5) superstring results in an inequivalent, so-called mirror theory that plays a central role in the field of integrability in the AdS-CFT correspondence. We show that this mirror theory can be interpreted as the light cone theory of a free string on a different background. This background is related to dS5×H(5) by a double T-duality, and has hidden supersymmetry. The geometry can also be extracted from an integrable deformation of the AdS5×S(5) sigma model, and we prove the observed mirror duality of these deformed models at the bosonic level as a byproduct. While we focus on AdS5×S(5), our results apply more generally.

  16. Sampling Strategy

    NASA Technical Reports Server (NTRS)

    2008-01-01

    Three locations to the right of the test dig area are identified for the first samples to be delivered to the Thermal and Evolved Gas Analyzer (TEGA), the Wet Chemistry Lab (WCL), and the Optical Microscope (OM) on NASA's Phoenix Mars Lander. These sampling areas are informally labeled 'Baby Bear', 'Mama Bear', and 'Papa Bear' respectively. This image was taken on the seventh day of the Mars mission, or Sol 7 (June 1, 2008) by the Surface Stereo Imager aboard NASA's Phoenix Mars Lander.

    The Phoenix Mission is led by the University of Arizona, Tucson, on behalf of NASA. Project management of the mission is by NASA's Jet Propulsion Laboratory, Pasadena, Calif. Spacecraft development is by Lockheed Martin Space Systems, Denver.

  17. Brain Tumor Symptoms

    MedlinePlus

    ... Types of Tumors Risk Factors Brain Tumor Statistics Brain Tumor Dictionary Webinars Anytime Learning About Us Our Founders Board of Directors Staff ... Types of Tumors Risk Factors Brain Tumor Statistics Brain Tumor Dictionary Webinars Anytime Learning Donate to the ABTA Help advance the understanding ...

  18. Brain ERP components predict which individuals progress to Alzheimer's disease and which do not.

    PubMed

    Chapman, Robert M; McCrary, John W; Gardner, Margaret N; Sandoval, Tiffany C; Guillily, Maria D; Reilly, Lindsey A; DeGrush, Elizabeth

    2011-10-01

    Predicting which individuals will progress to Alzheimer's disease (AD) is important in both clinical and research settings. We used brain Event-Related Potentials (ERPs) obtained in a perceptual/cognitive paradigm with various processing demands to predict which individual Mild Cognitive Impairment (MCI) subjects will develop AD versus which will not. ERP components, including P3, memory "storage" component, and other earlier and later components, were identified and measured by Principal Components Analysis. When measured for particular task conditions, a weighted set of eight ERP component_conditions performed well in discriminant analysis at predicting later AD progression with good accuracy, sensitivity, and specificity. The predictions for most individuals (79%) had high posterior probabilities and were accurate (88%). This method, supported by a cross-validation where the prediction accuracy was 70-78%, features the posterior probability for each individual as a method of determining the likelihood of progression to AD. Empirically obtained prediction accuracies rose to 94% when the computed posterior probabilities for individuals were 0.90 or higher (which was found for 40% of our MCI sample).

  19. Extractions of pyrroloquinoline quinone from crude biological samples.

    PubMed

    Suzuki, O; Kumazawa, T; Seno, H; Urakami, T; Matsumoto, T

    1990-01-01

    The best conditions for extractions of free pyrroloquinoline quinone (PQQ) from crude biological samples were investigated with various organic solvents and Sep-Pak C18 cartridges. PQQ was measured with use of its native fluorescence in aqueous solution. PQQ was well extracted into n-butanol under acid conditions, and addition of NaCl did not improve the solvent extraction. PQQ, which had been extracted into n-butanol, could be re-extracted into an aqueous phase by addition of either n-heptane or pyridine, or combination of them. PQQ, which had been adsorbed to Sep-Pak C18 cartridges, could be eluted with a mixture of pyridine and water with very excellent recovery. The recovery of 1 micrograms PQQ, which had been added to 1 g human liver, brain and 1 ml plasma and had undergone the n-butanol and the Sep-Pak extractions, was 50, 75 and 105%, respectively. From the blank fluorescence, endogenous levels of free PQQ in human liver, brain and plasma were found not greater than 0.41, 0.08 and 0.13 micrograms/g or ml, respectively, if present.

  20. Nanoparticle-mediated brain drug delivery: Overcoming blood-brain barrier to treat neurodegenerative diseases.

    PubMed

    Saraiva, Cláudia; Praça, Catarina; Ferreira, Raquel; Santos, Tiago; Ferreira, Lino; Bernardino, Liliana

    2016-08-10

    The blood-brain barrier (BBB) is a vital boundary between neural tissue and circulating blood. The BBB's unique and protective features control brain homeostasis as well as ion and molecule movement. Failure in maintaining any of these components results in the breakdown of this specialized multicellular structure and consequently promotes neuroinflammation and neurodegeneration. In several high incidence pathologies such as stroke, Alzheimer's (AD) and Parkinson's disease (PD) the BBB is impaired. However, even a damaged and more permeable BBB can pose serious challenges to drug delivery into the brain. The use of nanoparticle (NP) formulations able to encapsulate molecules with therapeutic value, while targeting specific transport processes in the brain vasculature, may enhance drug transport through the BBB in neurodegenerative/ischemic disorders and target relevant regions in the brain for regenerative processes. In this review, we will discuss BBB composition and characteristics and how these features are altered in pathology, namely in stroke, AD and PD. Additionally, factors influencing an efficient intravenous delivery of polymeric and inorganic NPs into the brain as well as NP-related delivery systems with the most promising functional outcomes will also be discussed.

  1. Acetazolamide Mitigates Astrocyte Cellular Edema Following Mild Traumatic Brain Injury

    NASA Astrophysics Data System (ADS)

    Sturdivant, Nasya M.; Smith, Sean G.; Ali, Syed F.; Wolchok, Jeffrey C.; Balachandran, Kartik

    2016-09-01

    Non-penetrating or mild traumatic brain injury (mTBI) is commonly experienced in accidents, the battlefield and in full-contact sports. Astrocyte cellular edema is one of the major factors that leads to high morbidity post-mTBI. Various studies have reported an upregulation of aquaporin-4 (AQP4), a water channel protein, following brain injury. AZA is an antiepileptic drug that has been shown to inhibit AQP4 expression and in this study we investigate the drug as a therapeutic to mitigate the extent of mTBI induced cellular edema. We hypothesized that mTBI-mediated astrocyte dysfunction, initiated by increased intracellular volume, could be reduced when treated with AZA. We tested our hypothesis in a three-dimensional in vitro astrocyte model of mTBI. Samples were subject to no stretch (control) or one high-speed stretch (mTBI) injury. AQP4 expression was significantly increased 24 hours after mTBI. mTBI resulted in a significant increase in the cell swelling within 30 min of mTBI, which was significantly reduced in the presence of AZA. Cell death and expression of S100B was significantly reduced when AZA was added shortly before mTBI stretch. Overall, our data point to occurrence of astrocyte swelling immediately following mTBI, and AZA as a promising treatment to mitigate downstream cellular mortality.

  2. Acetazolamide Mitigates Astrocyte Cellular Edema Following Mild Traumatic Brain Injury

    PubMed Central

    Sturdivant, Nasya M.; Smith, Sean G.; Ali, Syed F.; Wolchok, Jeffrey C.; Balachandran, Kartik

    2016-01-01

    Non-penetrating or mild traumatic brain injury (mTBI) is commonly experienced in accidents, the battlefield and in full-contact sports. Astrocyte cellular edema is one of the major factors that leads to high morbidity post-mTBI. Various studies have reported an upregulation of aquaporin-4 (AQP4), a water channel protein, following brain injury. AZA is an antiepileptic drug that has been shown to inhibit AQP4 expression and in this study we investigate the drug as a therapeutic to mitigate the extent of mTBI induced cellular edema. We hypothesized that mTBI-mediated astrocyte dysfunction, initiated by increased intracellular volume, could be reduced when treated with AZA. We tested our hypothesis in a three-dimensional in vitro astrocyte model of mTBI. Samples were subject to no stretch (control) or one high-speed stretch (mTBI) injury. AQP4 expression was significantly increased 24 hours after mTBI. mTBI resulted in a significant increase in the cell swelling within 30 min of mTBI, which was significantly reduced in the presence of AZA. Cell death and expression of S100B was significantly reduced when AZA was added shortly before mTBI stretch. Overall, our data point to occurrence of astrocyte swelling immediately following mTBI, and AZA as a promising treatment to mitigate downstream cellular mortality. PMID:27623738

  3. Acetazolamide Mitigates Astrocyte Cellular Edema Following Mild Traumatic Brain Injury.

    PubMed

    Sturdivant, Nasya M; Smith, Sean G; Ali, Syed F; Wolchok, Jeffrey C; Balachandran, Kartik

    2016-01-01

    Non-penetrating or mild traumatic brain injury (mTBI) is commonly experienced in accidents, the battlefield and in full-contact sports. Astrocyte cellular edema is one of the major factors that leads to high morbidity post-mTBI. Various studies have reported an upregulation of aquaporin-4 (AQP4), a water channel protein, following brain injury. AZA is an antiepileptic drug that has been shown to inhibit AQP4 expression and in this study we investigate the drug as a therapeutic to mitigate the extent of mTBI induced cellular edema. We hypothesized that mTBI-mediated astrocyte dysfunction, initiated by increased intracellular volume, could be reduced when treated with AZA. We tested our hypothesis in a three-dimensional in vitro astrocyte model of mTBI. Samples were subject to no stretch (control) or one high-speed stretch (mTBI) injury. AQP4 expression was significantly increased 24 hours after mTBI. mTBI resulted in a significant increase in the cell swelling within 30 min of mTBI, which was significantly reduced in the presence of AZA. Cell death and expression of S100B was significantly reduced when AZA was added shortly before mTBI stretch. Overall, our data point to occurrence of astrocyte swelling immediately following mTBI, and AZA as a promising treatment to mitigate downstream cellular mortality. PMID:27623738

  4. Twenty-first century brain banking. Processing brains for research: the Columbia University methods

    PubMed Central

    del Amaya, Maria Pilar; Keller, Christian E.

    2007-01-01

    Carefully categorized postmortem human brains are crucial for research. The lack of generally accepted methods for processing human postmortem brains for research persists. Thus, brain banking is essential; however, it cannot be achieved at the cost of the teaching mission of the academic institution by routing brains away from residency programs, particularly when the autopsy rate is steadily decreasing. A consensus must be reached whereby a brain can be utilizable for diagnosis, research, and teaching. The best diagnostic categorization possible must be secured and the yield of samples for basic investigation maximized. This report focuses on integrated, novel methods currently applied at the New York Brain Bank, Columbia University, New York, which are designed to reach accurate neuropathological diagnosis, optimize the yield of samples, and process fresh-frozen samples suitable for a wide range of modern investigations. The brains donated for research are processed as soon as possible after death. The prosector must have a good command of the neuroanatomy, neuropathology, and the protocol. One half of each brain is immersed in formalin for performing the thorough neuropathologic evaluation, which is combined with the teaching task. The contralateral half is extensively dissected at the fresh state. The anatomical origin of each sample is recorded using the map of Brodmann for the cortical samples. The samples are frozen at −160°C, barcode labeled, and ready for immediate disbursement once categorized diagnostically. A rigorous organization of freezer space, coupled to an electronic tracking system with its attached software, fosters efficient access for retrieval within minutes of any specific frozen samples in storage. This report describes how this achievement is feasible with emphasis on the actual processing of brains donated for research. PMID:17985145

  5. Higher spin contributions to holographic fluid dynamics in AdS5/CFT4

    NASA Astrophysics Data System (ADS)

    Lee, Seungjin; Polyakov, Dimitri

    2014-08-01

    We calculate the graviton's β function in the AdS string-theoretic sigma model, perturbed by vertex operators for Vasiliev's higher spin gauge fields in AdS5. The result is given by βmn=Rmn+4Tmn(g ,u) (with the AdS radius set to 1 and the graviton polarized along the AdS5 boundary), with the matter stress-energy tensor given by that of conformal holographic fluid in d =4, evaluated at the temperature given by T =1/π. The stress-energy tensor is given by Tmn=gmn+4umun+∑NTmn(N) where u is the vector excitation satisfying u2=-1 and N is the order of the gradient expansion in the dissipative part of the tensor. We calculate the contributions up to N =2. The higher spin excitations contribute to the β function, ensuring the overall Weyl covariance of the matter stress tensor. We conjecture that the structure of gradient expansion in d =4 conformal hydrodynamics at higher orders is controlled by the higher spin operator algebra in AdS5.

  6. AdS and Lifshitz scalar hairy black holes in Gauss-Bonnet gravity

    NASA Astrophysics Data System (ADS)

    Chen, Bin; Fan, Zhong-Ying; Zhu, Lu-Yao

    2016-09-01

    We consider Gauss-Bonnet (GB) gravity in general dimensions, which is nonminimally coupled to a scalar field. By choosing a scalar potential of the type V (ϕ )=2 Λ0+1/2 m2ϕ2+γ4ϕ4 , we first obtain large classes of scalar hairy black holes with spherical/hyperbolic/planar topologies that are asymptotic to locally anti- de Sitter (AdS) space-times. We derive the first law of black hole thermodynamics using Wald formalism. In particular, for one class of the solutions, the scalar hair forms a thermodynamic conjugate with the graviton and nontrivially contributes to the thermodynamical first law. We observe that except for one class of the planar black holes, all these solutions are constructed at the critical point of GB gravity where there exist unique AdS vacua. In fact, a Lifshitz vacuum is also allowed at the critical point. We then construct many new classes of neutral and charged Lifshitz black hole solutions for an either minimally or nonminimally coupled scalar and derive the thermodynamical first laws. We also obtain new classes of exact dynamical AdS and Lifshitz solutions which describe radiating white holes. The solutions eventually become AdS or Lifshitz vacua at late retarded times. However, for one class of the solutions, the final state is an AdS space-time with a globally naked singularity.

  7. Brain evolution by brain pathway duplication.

    PubMed

    Chakraborty, Mukta; Jarvis, Erich D

    2015-12-19

    Understanding the mechanisms of evolution of brain pathways for complex behaviours is still in its infancy. Making further advances requires a deeper understanding of brain homologies, novelties and analogies. It also requires an understanding of how adaptive genetic modifications lead to restructuring of the brain. Recent advances in genomic and molecular biology techniques applied to brain research have provided exciting insights into how complex behaviours are shaped by selection of novel brain pathways and functions of the nervous system. Here, we review and further develop some insights to a new hypothesis on one mechanism that may contribute to nervous system evolution, in particular by brain pathway duplication. Like gene duplication, we propose that whole brain pathways can duplicate and the duplicated pathway diverge to take on new functions. We suggest that one mechanism of brain pathway duplication could be through gene duplication, although other mechanisms are possible. We focus on brain pathways for vocal learning and spoken language in song-learning birds and humans as example systems. This view presents a new framework for future research in our understanding of brain evolution and novel behavioural traits.

  8. Brain evolution by brain pathway duplication

    PubMed Central

    Chakraborty, Mukta; Jarvis, Erich D.

    2015-01-01

    Understanding the mechanisms of evolution of brain pathways for complex behaviours is still in its infancy. Making further advances requires a deeper understanding of brain homologies, novelties and analogies. It also requires an understanding of how adaptive genetic modifications lead to restructuring of the brain. Recent advances in genomic and molecular biology techniques applied to brain research have provided exciting insights into how complex behaviours are shaped by selection of novel brain pathways and functions of the nervous system. Here, we review and further develop some insights to a new hypothesis on one mechanism that may contribute to nervous system evolution, in particular by brain pathway duplication. Like gene duplication, we propose that whole brain pathways can duplicate and the duplicated pathway diverge to take on new functions. We suggest that one mechanism of brain pathway duplication could be through gene duplication, although other mechanisms are possible. We focus on brain pathways for vocal learning and spoken language in song-learning birds and humans as example systems. This view presents a new framework for future research in our understanding of brain evolution and novel behavioural traits. PMID:26554045

  9. Brain evolution by brain pathway duplication.

    PubMed

    Chakraborty, Mukta; Jarvis, Erich D

    2015-12-19

    Understanding the mechanisms of evolution of brain pathways for complex behaviours is still in its infancy. Making further advances requires a deeper understanding of brain homologies, novelties and analogies. It also requires an understanding of how adaptive genetic modifications lead to restructuring of the brain. Recent advances in genomic and molecular biology techniques applied to brain research have provided exciting insights into how complex behaviours are shaped by selection of novel brain pathways and functions of the nervous system. Here, we review and further develop some insights to a new hypothesis on one mechanism that may contribute to nervous system evolution, in particular by brain pathway duplication. Like gene duplication, we propose that whole brain pathways can duplicate and the duplicated pathway diverge to take on new functions. We suggest that one mechanism of brain pathway duplication could be through gene duplication, although other mechanisms are possible. We focus on brain pathways for vocal learning and spoken language in song-learning birds and humans as example systems. This view presents a new framework for future research in our understanding of brain evolution and novel behavioural traits. PMID:26554045

  10. Biomechanics of brain tissue.

    PubMed

    Prevost, Thibault P; Balakrishnan, Asha; Suresh, Subra; Socrate, Simona

    2011-01-01

    The dynamic behavior of porcine brain tissue, obtained from a series of in vitro observations and experiments, is analyzed and described here with the aid of a large strain, nonlinear, viscoelastic constitutive model. Mixed gray and white matter samples excised from the superior cortex were tested in unconfined uniaxial compression within 15h post mortem. The test sequence consisted of three successive load-unload segments at strain rates of 1, 0.1 and 0.01 s⁻¹, followed by stress relaxation (n=25). The volumetric compliance of the tissue was assessed for a subset of specimens (n=7) using video extensometry techniques. The tissue response exhibited moderate compressibility, substantial nonlinearity, hysteresis, conditioning and rate dependence. A large strain kinematics nonlinear viscoelastic model was developed to account for the essential features of the tissue response over the entire deformation history. The corresponding material parameters were obtained by fitting the model to the measured conditioned response (axial and volumetric) via a numerical optimization scheme. The model successfully captures the observed complexities of the material response in loading, unloading and relaxation over the entire range of strain rates. The accuracy of the model was further verified by comparing model predictions with the tissue response in unconfined compression at higher strain rate (10 s⁻¹) and with literature data in uniaxial tension. The proposed constitutive framework was also found to be adequate to model the loading response of brain tissue in uniaxial compression over a wider range of strain rates (0.01-3000 s⁻¹), thereby providing a valuable tool for simulations of dynamic transients (impact, blast/shock wave propagation) leading to traumatic brain injury.

  11. Obesity and age-related alterations in the gene expression of zinc-transporter proteins in the human brain.

    PubMed

    Olesen, R H; Hyde, T M; Kleinman, J E; Smidt, K; Rungby, J; Larsen, A

    2016-01-01

    The incidence of Alzheimer's disease (AD) is increasing. Major risk factors for AD are advancing age and diabetes. Lately, obesity has been associated with an increased risk of dementia. Obese and diabetic individuals are prone to decreased circulating levels of zinc, reducing the amount of zinc available for crucial intracellular processes. In the brain, zinc co-localizes with glutamate in synaptic vesicles, and modulates NMDA receptor activity. Intracellular zinc is involved in apoptosis and fluctuations in cytoplasmic Zn(2+) affect modulation of intracellular signaling. The ZNT and ZIP proteins participate in intracellular zinc homeostasis. Altered expression of zinc-regulatory proteins has been described in AD patients. Using microarray data from human frontal cortex (BrainCloud), this study investigates expression of the SCLA30A (ZNT) and SCLA39A (ZIP) families of genes in a Caucasian and African-American sample of 145 neurologically and psychiatrically normal individuals. Expression of ZNT3 and ZNT4 were significantly reduced with increasing age, whereas expression of ZIP1, ZIP9 and ZIP13 were significantly increased. Increasing body mass index (BMI) correlated with a significant reduction in ZNT1 expression similar to what is seen in the early stages of AD. Increasing BMI also correlated with reduced expression of ZNT6. In conclusion, we found that the expression of genes that regulate intracellular zinc homeostasis in the human frontal cortex is altered with increasing age and affected by increasing BMI. With the increasing rates of obesity throughout the world, these findings warrant continuous scrutiny of the long-term consequences of obesity on brain function and the development of neurodegenerative diseases. PMID:27300264

  12. Obesity and age-related alterations in the gene expression of zinc-transporter proteins in the human brain

    PubMed Central

    Olesen, R H; Hyde, T M; Kleinman, J E; Smidt, K; Rungby, J; Larsen, A

    2016-01-01

    The incidence of Alzheimer's disease (AD) is increasing. Major risk factors for AD are advancing age and diabetes. Lately, obesity has been associated with an increased risk of dementia. Obese and diabetic individuals are prone to decreased circulating levels of zinc, reducing the amount of zinc available for crucial intracellular processes. In the brain, zinc co-localizes with glutamate in synaptic vesicles, and modulates NMDA receptor activity. Intracellular zinc is involved in apoptosis and fluctuations in cytoplasmic Zn2+ affect modulation of intracellular signaling. The ZNT and ZIP proteins participate in intracellular zinc homeostasis. Altered expression of zinc-regulatory proteins has been described in AD patients. Using microarray data from human frontal cortex (BrainCloud), this study investigates expression of the SCLA30A (ZNT) and SCLA39A (ZIP) families of genes in a Caucasian and African-American sample of 145 neurologically and psychiatrically normal individuals. Expression of ZNT3 and ZNT4 were significantly reduced with increasing age, whereas expression of ZIP1, ZIP9 and ZIP13 were significantly increased. Increasing body mass index (BMI) correlated with a significant reduction in ZNT1 expression similar to what is seen in the early stages of AD. Increasing BMI also correlated with reduced expression of ZNT6. In conclusion, we found that the expression of genes that regulate intracellular zinc homeostasis in the human frontal cortex is altered with increasing age and affected by increasing BMI. With the increasing rates of obesity throughout the world, these findings warrant continuous scrutiny of the long-term consequences of obesity on brain function and the development of neurodegenerative diseases. PMID:27300264

  13. Robotic multimodality stereotactic brain tissue identification: work in progress

    NASA Technical Reports Server (NTRS)

    Andrews, R.; Mah, R.; Galvagni, A.; Guerrero, M.; Papasin, R.; Wallace, M.; Winters, J.

    1997-01-01

    Real-time identification of tissue would improve procedures such as stereotactic brain biopsy (SBX), functional and implantation neurosurgery, and brain tumor excision. To standard SBX equipment has been added: (1) computer-controlled stepper motors to drive the biopsy needle/probe precisely; (2) multiple microprobes to track tissue density, detect blood vessels and changes in blood flow, and distinguish the various tissues being penetrated; (3) neural net learning programs to allow real-time comparisons of current data with a normative data bank; (4) three-dimensional graphic displays to follow the probe as it traverses brain tissue. The probe can differentiate substances such as pig brain, differing consistencies of the 'brain-like' foodstuff tofu, and gels made to simulate brain, as well as detect blood vessels imbedded in these substances. Multimodality probes should improve the safety, efficacy, and diagnostic accuracy of SBX and other neurosurgical procedures.

  14. Spinning strings at one-loop in AdS4 × Bbb P3

    NASA Astrophysics Data System (ADS)

    McLoughlin, Tristan; Roiban, Radu

    2008-12-01

    We analyze the folded spinning string in AdS4 × Bbb P3 with spin S in AdS4 and angular momentum J in Bbb P3. We calculate the one-loop correction to its energy in the scaling limit of both ln S and J large with their ratio kept fixed. This result should correspond to the first subleading strong coupling correction to the anomalous dimension of operators of the type Tr(DS(Y†Y)J) in the dual Script N = 6 Chern-Simons-matter theory. Our result appears to depart from the predictions for the generalized scaling function found from the all-loop Bethe equations conjectured for this AdS4/CFT3 duality. We comment on the possible origin of this difference.

  15. A stochasticity threshold in holography and the instability of AdS

    NASA Astrophysics Data System (ADS)

    Basu, Pallab; Krishnan, Chethan; Saurabh, Ayush

    2015-07-01

    We give strong numerical evidence that a self-interacting probe scalar field in AdS, with only a few modes turned on initially, will undergo fast thermalization only if it is above a certain energetic threshold. Below the threshold the energy stays close to constant in a few modes for a very long time instead of cascading quickly. This indicates the existence of a Strong Stochasticity Threshold (SST) in holography. The idea of SST is familiar from certain statistical mechanical systems, and we suggest that it exists also in AdS gravity. This would naturally reconcile the generic nonlinear instability of AdS observed by Bizon and Rostworowski, with the Fermi-Pasta-Ulam-Tsingou-like quasiperiodicity noticed recently for some classes of initial conditions. We show that our simple setup captures many of the relevant features of the full gravity-scalar system.

  16. QCD Condensates and Holographic Wilson Loops for Asymptotically AdS Spaces

    SciTech Connect

    Quevedo, R. Carcasses; Goity, Jose L.; Trinchero, Roberto C.

    2014-02-01

    The minimization of the Nambu-Goto (NG) action for a surface whose contour defines a circular Wilson loop of radius a placed at a finite value of the coordinate orthogonal to the border is considered. This is done for asymptotically AdS spaces. The condensates of dimension n = 2, 4, 6, 8, and 10 are calculated in terms of the coefficients in the expansion in powers of the radius a of the on-shell subtracted NG action for small a->0. The subtraction employed is such that it presents no conflict with conformal invariance in the AdS case and need not introduce an additional infrared scale for the case of confining geometries. It is shown that the UV value of the gluon condensates is universal in the sense that it only depends on the first coefficients of the difference with the AdS case.

  17. Asymptotically AdS Solutions of Five Dimensional Gravity-Dilaton Theory

    NASA Astrophysics Data System (ADS)

    Nata Atmaja, Ardian

    2016-08-01

    We search for Asymptotically AdS solutions of the background metric in which dilaton back reacts to gravity in five-dimensional gravity-dilaton theory. The five-dimensional gravity-dilaton theory generally appears in the context of the low energy effective action of closed string theory in the Einstein frame. In particular, we consider dilaton which are minimally coupled to gravity in which the potential for dilation is taken to be simple and contain only one exponential term parametrized by a constant a. We solve analytically and show for a simple constant dilaton potential it appears there are no black hole solutions if we turn on the dilaton contribution. On the other hand, the exponential dilaton potential has black hole solutions but they are not in general Asymptotically AdS. We argue that there are some possible Asymptotically AdS black hole solutions in the range of |a| \\lt \\frac{4}{\\sqrt{6}}

  18. Superstring theory on AdS 2× S2 as a coset supermanifold

    NASA Astrophysics Data System (ADS)

    Berkovits, N.; Bershadsky, M.; Hauer, T.; Zhukov, S.; Zwiebach, B.

    We quantize the superstring on the AdS 2× S2 background with Ramond-Ramond flux using a PSU(1,1|2)/ U(1)× U(1) sigma model with a WZ term. One-loop conformal invariance of the model is guaranteed by a general mechanism which holds for coset spaces G/ H where G is Ricci-flat and H is the invariant locus of a Z4 automorphism of G. This mechanism gives conformal theories for the PSU(1,1|2)× PSU(2|2)/ SU(2)× SU(2) and PSU(2,2|4)/ SO(4,1)× SO(5) coset spaces, suggesting our results might be useful for quantizing the superstring on AdS 3× S3 and AdS 5× S5 backgrounds.

  19. Photon gas thermodynamics in dS and AdS momentum spaces

    NASA Astrophysics Data System (ADS)

    Gorji, M. A.; Hosseinzadeh, V.; Nozari, K.; Vakili, B.

    2016-07-01

    In this paper, we study thermostatistical properties of a photon gas in the framework of two deformed special relativity models defined by the cosmological coordinatizations of the de Sitter (dS) and anti-de Sitter (AdS) momentum spaces. The dS model is a doubly special relativity theory in which an ultraviolet length scale is invariant under the deformed Lorentz transformations. For the case of the AdS model, however, the Lorentz symmetry breaks at the high energy regime. We show that the existence of a maximal momentum in dS momentum space leads to maximal pressure and temperature at the thermodynamical level, while maximal internal energy and entropy arise for the case of the AdS momentum space due to the existence of a maximal kinematical energy. These results show that the thermodynamical duality of these models is very similar to their well-known kinematical duality.

  20. Neuropathologic features of Aleutian disease in farmed mink in Ireland and molecular characterization of Aleutian mink disease virus detected in brain tissues.

    PubMed

    Jahns, Hanne; Daly, Paul; McElroy, Maire C; Sammin, Donal J; Bassett, Hugh F; Callanan, John J

    2010-01-01

    A neuropathologic survey was conducted on mink brains from the 5 licensed mink farms in Ireland. The survey was part of a transmissible spongiform encephalopathy surveillance study. Aleutian disease (AD) was present on 4 of the 5 farms (80%). Neuropathologic features of nonsuppurative meningoencephalitis were common in mink from the 4 affected farms but were absent in the mink from the fifth farm, which was free of AD. The meningoencephalitis was characterized by infiltrates of lymphocytes and plasma cells, which were present in meninges, perivascular spaces, and the brain parenchyma. Fibrinoid necrotizing arteritis was seen in 11 mink brains, all of which were obtained from a single farm. Aleutian mink disease virus (AMDV) sequences for the capsid protein VP2 were obtained from brain samples from all affected farms. Although containing previously unreported amino acid residues, similarities with European and North American isolates were observed in the hypervariable regions within VP2, suggesting Irish AMDV is related to those isolates. The predicted amino acid residues, suspected of conferring pathogenicity at certain positions of the VP2 sequence, were present in the viral nucleic acid sequences. PMID:20093694

  1. Interpolating from Bianchi attractors to Lifshitz and AdS spacetimes

    NASA Astrophysics Data System (ADS)

    Kachru, Shamit; Kundu, Nilay; Saha, Arpan; Samanta, Rickmoy; Trivedi, Sandip P.

    2014-03-01

    We construct classes of smooth metrics which interpolate from Bianchi attractor geometries of Types II, III, VI and IX in the IR to Lifshitz or AdS 2 × S 3 geometries in the UV. While we do not obtain these metrics as solutions of Einstein gravity coupled to a simple matter field theory, we show that the matter sector stress-energy required to support these geometries (via the Einstein equations) does satisfy the weak, and therefore also the null, energy condition. Since Lifshitz or AdS 2 × S 3 geometries can in turn be connected to AdS 5 spacetime, our results show that there is no barrier, at least at the level of the energy conditions, for solutions to arise connecting these Bianchi attractor geometries to AdS 5 spacetime. The asymptotic AdS 5 spacetime has no non-normalizable metric deformation turned on, which suggests that furthermore, the Bianchi attractor geometries can be the IR geometries dual to field theories living in flat space, with the breaking of symmetries being either spontaneous or due to sources for other fields. Finally, we show that for a large class of flows which connect two Bianchi attractors, a C-function can be defined which is monotonically decreasing from the UV to the IR as long as the null energy condition is satisfied. However, except for special examples of Bianchi attractors (including AdS space), this function does not attain a finite and non-vanishing constant value at the end points.

  2. Computing and Using Metrics in the ADS

    NASA Astrophysics Data System (ADS)

    Henneken, E. A.; Accomazzi, A.; Kurtz, M. J.; Grant, C. S.; Thompson, D.; Luker, J.; Chyla, R.; Holachek, A.; Murray, S. S.

    2015-04-01

    Finding measures for research impact, be it for individuals, institutions, instruments, or projects, has gained a lot of popularity. There are more papers written than ever on new impact measures, and problems with existing measures are being pointed out on a regular basis. Funding agencies require impact statistics in their reports, job candidates incorporate them in their resumes, and publication metrics have even been used in at least one recent court case. To support this need for research impact indicators, the SAO/NASA Astrophysics Data System (ADS) has developed a service that provides a broad overview of various impact measures. In this paper we discuss how the ADS can be used to quench the thirst for impact measures. We will also discuss a couple of the lesser-known indicators in the metrics overview and the main issues to be aware of when compiling publication-based metrics in the ADS, namely author name ambiguity and citation incompleteness.

  3. Perceptions, Knowledge, Incentives, and Barriers of Brain Donation among African American Elders Enrolled in an Alzheimer's Research Program

    ERIC Educational Resources Information Center

    Lambe, Susan; Cantwell, Nicole; Islam, Fareesa; Horvath, Kathy; Jefferson, Angela L.

    2011-01-01

    Purpose: To learn about African American older adults' knowledge and perceptions of brain donation, factors that relate to participating or not participating in a brain donation research program, and methods to increase African American brain donation commitment rates in the context of an Alzheimer's disease (AD) research program. Design and…

  4. Flowing along the edge: Spinning up black holes in AdS spacetimes with test particles

    NASA Astrophysics Data System (ADS)

    Rocha, Jorge V.; Santarelli, Raphael

    2014-03-01

    We investigate the consequences of throwing point particles into odd-dimensional Myers-Perry black holes in asymptotically anti-de Sitter (AdS) backgrounds. We restrict our attention to the case in which the angular momenta of the background geometry are all equal. This process allows us to test the generalization of the weak cosmic censorship conjecture to asymptotically AdS spacetimes in higher dimensions. We find no evidence for overspinning in D =5,7,9 and 11 dimensions. Instead, test particles carrying the maximum possible angular momentum that still fall into an extremal rotating black hole generate a flow along the curve of extremal solutions.

  5. FAST TRACK COMMUNICATION: The hidden symmetry of higher dimensional Kerr NUT AdS spacetimes

    NASA Astrophysics Data System (ADS)

    Kubiznák, David; Frolov, Valeri P.

    2007-02-01

    It is well known that four-dimensional Kerr NUT AdS spacetime possesses the hidden symmetry associated with the Killing Yano tensor. This tensor is 'universal' in the sense that there exist coordinates where it does not depend on any of the free parameters of the metric. Recently, the general higher dimensional Kerr NUT AdS solutions of the Einstein equations were obtained. We demonstrate that all these metrics with arbitrary rotation and NUT parameters admit a universal Killing Yano tensor. We give an explicit presentation of the Killing Yano tensor and associated second rank Killing tensor and briefly discuss their properties.

  6. {{AdS}}_{3}/{{CFT}}_{2} and q-Poincaré superalgebras

    NASA Astrophysics Data System (ADS)

    Strömwall, Joakim; Torrielli, Alessandro

    2016-10-01

    We discover that a certain deformation of the 1+1 dimensional Poincaré superalgebra is exactly realised in the massless sector of the {{AdS}}3/{{CFT}}2 integrable scattering problem. Deformed Poincaré superalgebras were previously noticed to appear in the {{AdS}}5/{{CFT}}4 correspondence—which displays only massive excitations, but they were there only a partial symmetry. We obtain a representation of the boost operator and its coproduct, and show that the comultiplication exactly satisfies the homomorphism property. We present a classical limit, and finally speculate on an analogy with the physics of phonons.

  7. New Features in the ADS Abstract Service

    NASA Astrophysics Data System (ADS)

    Eichhorn, G.; Accomazzi, A.; Grant, C. S.; Kurtz, M. J.; ReyBacaicoa, V.; Murray, S. S.

    2001-11-01

    The ADS Abstract Service contains over 2.3 million references in four databases: Astronomy/Astrophysics/Planetary Sciences, Instrumentation, Physics/Geophysics, and Preprints. We provide abstracts and articles free to the astronomical community for all major and many smaller astronomy journals, PhD theses, conference proceedings, and technical reports. These four databases can be queried either separately of jointly. The ADS also has scanned 1.3 million pages in 180,000 articles in the ADS Article Service. This literature archive contains all major Astronomy journals and many smaller journals, as well as conference proceedings, including the abstract books from all the LPSCs back to volume 2. A new feature gives our users the ability to see list of articles that were also read by the readers of a given article. This is a powerful tool to find out what current articles are relevant in a particular field of study. We have recently expanded the citation and reference query capabilities. It allows our users to select papers for which they want to see references or citations and then retrieve these citations/references. Another new capability is the ability to sort a list of articles by their citation count. As usual, users should be reminded that the citations in ADS are incomplete because we do not obtain reference lists from all publishers. In addition, we cannot match all references (e.g. in press, private communications, author errors, some conference papers, etc.). Anyone using the citations for analysis of publishing records should keep this in mind. More work on expanding the citation and reference features is planned over the next year. ADS Home Page http://ads.harvard.edu/

  8. Early complement components in Alzheimer's disease brains.

    PubMed

    Veerhuis, R; Janssen, I; Hack, C E; Eikelenboom, P

    1996-01-01

    Activation products of the early complement components C1, C4 and C3 can be found colocalized with diffuse and fibrillar beta-amyloid (beta/A4) deposits in Alzheimer's disease (AD) brains. Immunohistochemically, C1-esterase inhibitor (C1-Inh) and the C1 subcomponents C1s and C1r can not, or only occasionally, be detected in plaques or in astrocytes. The present finding that C1q, C1s and C1-Inh mRNA are present in both AD and control brains suggests that the variable immunohistochemical staining results for C1r, C1s and C1-Inh are due to a rapid consumption, and that the inability to detect C1s, C1r or C1-Inh is probably due to the dissociation of C1s-C1-Inh and C1r-C1-Inh complexes from the activator-bound C1q into the fluid phase. Employing monoclonal antibodies specific for different forms of C1-Inh, no complexed C1-Inh could be found, whereas inactivated C1-Inh seems to be present in astrocytes surrounding beta/A4 plaques in AD brains. These findings, together with our finding (using reverse transcriptase-polymerase chain reaction) that C1-Inh is locally produced in the brain, suggest that in the brain complement activation at the C1 level is regulated by C1-Inh. Immunohistochemically, no evidence for the presence of the late complement components C5, C7 and C9, or of the membrane attack complex (MAC), was found in beta/A4 plaques. In contrast to the mRNA encoding the early components, that of the late complement components appears to be hardly detectable (C7) or absent (C9). Thus, without blood-brain-barrier impairment, the late complement components are probably present at too low a concentration to allow the formation of the MAC, which is generally believed to be responsible for at least some of the neurodegenerative effects observed in AD. Therefore, the present findings support the idea that in AD, complement does not function as an inflammatory mediator through MAC formation, but through the action of early component activation products.

  9. Preclinical Properties of 18F-AV-45: A PET Agent for Aβ Plaques in the Brain

    PubMed Central

    Choi, Seok Rye; Golding, Geoff; Zhuang, Zhiping; Zhang, Wei; Lim, Nathaniel; Hefti, Franz; Benedum, Tyler E.; Kilbourn, Michael R.; Skovronsky, Daniel; Kung, Hank F.

    2011-01-01

    β-amyloid plaques (Aβ plaques) in the brain, containing predominantly fibrillary Aβ peptide aggregates, represent a defining pathologic feature of Alzheimer disease (AD). Imaging agents targeting the Aβ plaques in the living human brain are potentially valuable as biomarkers of pathogenesis processes in AD. (E)-4-(2-(6-(2-(2-(2-18F-fluoroethoxy)ethoxy)ethoxy)pyridin-3-yl)vinyl)-N-methyl benzenamine (18F-AV-45) is such as an agent currently in phase III clinical studies for PET of Aβ plaques in the brain. Methods In vitro binding of 18F-AV-45 to Aβ plaques in the postmortem AD brain tissue was evaluated by in vitro binding assay and autoradiography. In vivo biodistribution of 18F-AV-45 in mice and ex vivo autoradiography of AD transgenic mice (APPswe/PSEN1) with Aβ aggregates in the brain were performed. Small-animal PET of a monkey brain after an intravenous injection of 18F-AV-45 was evaluated. Results 18F-AV-45 displayed a high binding affinity and specificity to Aβ plaques (Kd, 3.72 ± 0.30 nM). In vitro autoradiography of postmortem human brain sections showed substantial plaque labeling in AD brains and not in the control brains. Initial high brain uptake and rapid washout from the brain of healthy mice and monkey were observed. Metabolites produced in the blood of healthy mice after an intravenous injection were identified. 18F-AV-45 displayed excellent binding affinity to Aβ plaques in the AD brain by ex vivo autoradiography in transgenic AD model mice. The results lend support that 18F-AV-45 may be a useful PET agent for detecting Aβ plaques in the living human brain. PMID:19837759

  10. Added sugar intake and cardiovascular diseases mortality among US adults.

    PubMed

    Yang, Quanhe; Zhang, Zefeng; Gregg, Edward W; Flanders, W Dana; Merritt, Robert; Hu, Frank B

    2014-04-01

    IMPORTANCE Epidemiologic studies have suggested that higher intake of added sugar is associated with cardiovascular disease (CVD) risk factors. Few prospective studies have examined the association of added sugar intake with CVD mortality. OBJECTIVE To examine time trends of added sugar consumption as percentage of daily calories in the United States and investigate the association of this consumption with CVD mortality. DESIGN, SETTING, AND PARTICIPANTS National Health and Nutrition Examination Survey (NHANES, 1988-1994 [III], 1999-2004, and 2005-2010 [n = 31,147]) for the time trend analysis and NHANES III Linked Mortality cohort (1988-2006 [n = 11 733]), a prospective cohort of a nationally representative sample of US adults for the association study. MAIN OUTCOMES AND MEASURES Cardiovascular disease mortality. RESULTS Among US adults, the adjusted mean percentage of daily calories from added sugar increased from 15.7% (95% CI, 15.0%-16.4%) in 1988-1994 to 16.8% (16.0%-17.7%; P = .02) in 1999-2004 and decreased to 14.9% (14.2%-15.5%; P < .001) in 2005-2010. Most adults consumed 10% or more of calories from added sugar (71.4%) and approximately 10% consumed 25% or more in 2005-2010. During a median follow-up period of 14.6 years, we documented 831 CVD deaths during 163,039 person-years. Age-, sex-, and race/ethnicity-adjusted hazard ratios (HRs) of CVD mortality across quintiles of the percentage of daily calories consumed from added sugar were 1.00 (reference), 1.09 (95% CI, 1.05-1.13), 1.23 (1.12-1.34), 1.49 (1.24-1.78), and 2.43 (1.63-3.62; P < .001), respectively. After additional adjustment for sociodemographic, behavioral, and clinical characteristics, HRs were 1.00 (reference), 1.07 (1.02-1.12), 1.18 (1.06-1.31), 1.38 (1.11-1.70), and 2.03 (1.26-3.27; P = .004), respectively. Adjusted HRs were 1.30 (95% CI, 1.09-1.55) and 2.75 (1.40-5.42; P = .004), respectively, comparing participants who consumed 10.0% to 24.9% or 25.0% or

  11. Functional brain networks in Alzheimer's disease: EEG analysis based on limited penetrable visibility graph and phase space method

    NASA Astrophysics Data System (ADS)

    Wang, Jiang; Yang, Chen; Wang, Ruofan; Yu, Haitao; Cao, Yibin; Liu, Jing

    2016-10-01

    In this paper, EEG series are applied to construct functional connections with the correlation between different regions in order to investigate the nonlinear characteristic and the cognitive function of the brain with Alzheimer's disease (AD). First, limited penetrable visibility graph (LPVG) and phase space method map single EEG series into networks, and investigate the underlying chaotic system dynamics of AD brain. Topological properties of the networks are extracted, such as average path length and clustering coefficient. It is found that the network topology of AD in several local brain regions are different from that of the control group with no statistically significant difference existing all over the brain. Furthermore, in order to detect the abnormality of AD brain as a whole, functional connections among different brain regions are reconstructed based on similarity of clustering coefficient sequence (CCSS) of EEG series in the four frequency bands (delta, theta, alpha, and beta), which exhibit obvious small-world properties. Graph analysis demonstrates that for both methodologies, the functional connections between regions of AD brain decrease, particularly in the alpha frequency band. AD causes the graph index complexity of the functional network decreased, the small-world properties weakened, and the vulnerability increased. The obtained results show that the brain functional network constructed by LPVG and phase space method might be more effective to distinguish AD from the normal control than the analysis of single series, which is helpful for revealing the underlying pathological mechanism of the disease.

  12. (Pre)diabetes, brain aging, and cognition.

    PubMed

    S Roriz-Filho, Jarbas; Sá-Roriz, Ticiana M; Rosset, Idiane; Camozzato, Ana L; Santos, Antonio C; Chaves, Márcia L F; Moriguti, Júlio César; Roriz-Cruz, Matheus

    2009-05-01

    Cognitive dysfunction and dementia have recently been proven to be common (and underrecognized) complications of diabetes mellitus (DM). In fact, several studies have evidenced that phenotypes associated with obesity and/or alterations on insulin homeostasis are at increased risk for developing cognitive decline and dementia, including not only vascular dementia, but also Alzheimer's disease (AD). These phenotypes include prediabetes, diabetes, and the metabolic syndrome. Both types 1 and 2 diabetes are also important risk factors for decreased performance in several neuropsychological functions. Chronic hyperglycemia and hyperinsulinemia primarily stimulates the formation of Advanced Glucose Endproducts (AGEs), which leads to an overproduction of Reactive Oxygen Species (ROS). Protein glycation and increased oxidative stress are the two main mechanisms involved in biological aging, both being also probably related to the etiopathogeny of AD. AD patients were found to have lower than normal cerebrospinal fluid levels of insulin. Besides its traditional glucoregulatory importance, insulin has significant neurothrophic properties in the brain. How can clinical hyperinsulinism be a risk factor for AD whereas lab experiments evidence insulin to be an important neurothrophic factor? These two apparent paradoxal findings may be reconciliated by evoking the concept of insulin resistance. Whereas insulin is clearly neurothrophic at moderate concentrations, too much insulin in the brain may be associated with reduced amyloid-beta (Abeta) clearance due to competition for their common and main depurative mechanism - the Insulin-Degrading Enzyme (IDE). Since IDE is much more selective for insulin than for Abeta, brain hyperinsulinism may deprive Abeta of its main clearance mechanism. Hyperglycemia and hyperinsulinemia seems to accelerate brain aging also by inducing tau hyperphosphorylation and amyloid oligomerization, as well as by leading to widespread brain microangiopathy

  13. Cerebral insulin, insulin signaling pathway, and brain angiogenesis.

    PubMed

    Zeng, Yi; Zhang, Le; Hu, Zhiping

    2016-01-01

    Insulin performs unique non-metabolic functions within the brain. Broadly speaking, two major areas of these functions are those related to brain endothelial cells and the blood-brain barrier (BBB) function, and those related to behavioral effects, like cognition in disease states (Alzheimer's disease, AD) and in health. Recent studies showed that both these functions are associated with brain angiogenesis. These findings raise interesting questions such as how they are linked to each other and whether modifying brain angiogenesis by targeting certain insulin signaling pathways could be an effective strategy to treat dementia as in AD, or even to help secure healthy longevity. The two canonical downstream pathways involved in mediating the insulin signaling pathway, the phosphoinositide-3 kinase (PI3K), and mitogen-activated protein kinase (MAPK) cascades, in the brain are supposed to be similar to those in the periphery. PI3K and MAPK pathways play important roles in angiogenesis. Both are involved in stimulating hypoxia inducible factor (HIF) in angiogenesis and could be activated by the insulin signaling pathway. This suggests that PI3K and MAPK pathways might act as cross-talk between the insulin signaling pathway and the angiogenesis pathway in brain. But the cerebral insulin, insulin signaling pathway, and the detailed mechanism in the connection of insulin signaling pathway, brain angiogenesis pathway, and healthy aging or dementias are still mostly not clear and need further studies.

  14. Total, added, and free sugars: are restrictive guidelines science-based or achievable?

    PubMed

    Erickson, Jennifer; Slavin, Joanne

    2015-04-01

    Sugar consumption, especially added sugars, is under attack. Various government and health authorities have suggested new sugar recommendations and guidelines as low as 5% of total calories from free sugars. Definitions for total sugars, free sugars, and added sugars are not standardized, nor are there accepted nutrient databases for this information. Our objective was to measure total sugars and added sugars in sample meal plans created by the United States Department of Agriculture (USDA) and the Academy of Nutrition and Dietetics (AND). Utilizing the Nutrition Data System for Research (NDSR) nutritional database, results found that plans created by the USDA and AND averaged 5.1% and 3.1% calories from added sugar, 8.7% and 3.1% from free sugar, and 23.3% and 21.1% as total sugars respectively. Compliance with proposed added sugar recommendations would require strict dietary compliance and may not be sustainable for many Americans. Without an accepted definition and equation for calculating added sugar, added sugar recommendations are arbitrary and may reduce intakes of nutrient-rich, recommended foods, such as yogurt, whole grains, and tart fruits including cranberries, cherries, and grapefruit. Added sugars are one part of excess calorie intake; however, compliance with low added sugar recommendations may not be achievable for the general public. PMID:25884659

  15. Total, added, and free sugars: are restrictive guidelines science-based or achievable?

    PubMed

    Erickson, Jennifer; Slavin, Joanne

    2015-04-15

    Sugar consumption, especially added sugars, is under attack. Various government and health authorities have suggested new sugar recommendations and guidelines as low as 5% of total calories from free sugars. Definitions for total sugars, free sugars, and added sugars are not standardized, nor are there accepted nutrient databases for this information. Our objective was to measure total sugars and added sugars in sample meal plans created by the United States Department of Agriculture (USDA) and the Academy of Nutrition and Dietetics (AND). Utilizing the Nutrition Data System for Research (NDSR) nutritional database, results found that plans created by the USDA and AND averaged 5.1% and 3.1% calories from added sugar, 8.7% and 3.1% from free sugar, and 23.3% and 21.1% as total sugars respectively. Compliance with proposed added sugar recommendations would require strict dietary compliance and may not be sustainable for many Americans. Without an accepted definition and equation for calculating added sugar, added sugar recommendations are arbitrary and may reduce intakes of nutrient-rich, recommended foods, such as yogurt, whole grains, and tart fruits including cranberries, cherries, and grapefruit. Added sugars are one part of excess calorie intake; however, compliance with low added sugar recommendations may not be achievable for the general public.

  16. Docosahexaenoic acid homeostasis, brain aging and Alzheimer's disease: Can we reconcile the evidence?

    PubMed

    Cunnane, Stephen C; Chouinard-Watkins, Raphael; Castellano, Christian A; Barberger-Gateau, Pascale

    2013-01-01

    A crossroads has been reached on research into docosahexaenoic acid (DHA) and Alzheimer's disease (AD). On the one hand, several prospective observational studies now clearly indicate a protective effect of higher fish and DHA intake against risk of AD. On the other hand, once AD is clinically evident, supplementation trials demonstrate essentially no benefit of DHA in AD. Despite apparently low DHA intake in AD, brain DHA levels are frequently the same as in controls, suggesting that low DHA intake results in low plasma DHA but does not necessarily reduce brain DHA in humans. Animal models involving dietary omega-3 fatty acid deficiency to deplete brain DHA may therefore not be appropriate in AD research. Studies in the healthy elderly suggest that DHA homeostasis changes during aging. Tracer methodology now permits estimation of DHA half-life in the human brain and whole body. Apolipoprotein E alleles have an important impact not only on AD but also on DHA homeostasis in humans. We therefore encourage further development of innovative approaches to the study of DHA metabolism and its role in human brain function. A better understanding of DHA metabolism in humans will hopefully help explain how higher habitual DHA intake protects against the risk of deteriorating cognition during aging and may eventually give rise to a breakthrough in the treatment of AD. PMID:22575581

  17. MR diffusion tensor imaging (DTI) and neuropsychological testing for neuronal connectivity in Alzheimer's disease (AD) patients

    NASA Astrophysics Data System (ADS)

    Zhong, Jianhui; Ni, Hongyan; Zhu, Tong; Ekholm, Sven; Kavcic, Voyko

    2004-04-01

    We have used MR DTI to identify relevant brain structures involved in visuospatial processing, in an attempt to link perceptual and attentional impairments to WM changes in Alzheimer's disease (AD) patients. Correlation of DTI measured parameters with results of several neuropsychological tests will be reported here. Several issues related to quantitation of DTI parameters in ROI analysis are addressed. In spite of only a small number of subjects were studied so far, we found not only that AD patients showed significant decrease of white matter (WM) integrity in corpus callosum (CC), most prominent at the posterior portion, but also found significant correlations between the DTI parameters and scores from several neuropsychological tests. Our preliminary results suggest that DTI help to improve the overall accuracy rate in distinguishing between early AD onset and age-related functional decline, and potentially may improve efficiency in differentiating between different types of dementia.

  18. Offset compensation for A/D converters

    NASA Technical Reports Server (NTRS)

    Brokl, S. S.; Hurd, W. J.

    1979-01-01

    Analog-to-digital (A/D) converter eliminates dc offset in final digitized signal as well as in analog input by using digital feedback for compensation. Circuit could prove useful in data processing applications in which analog-format data are entered at high rates, as in point-of-sale data input systems.

  19. Value-Added Modeling in Physical Education

    ERIC Educational Resources Information Center

    Hushman, Glenn; Hushman, Carolyn

    2015-01-01

    The educational reform movement in the United States has resulted in a variety of states moving toward a system of value-added modeling (VAM) to measure a teacher's contribution to student achievement. Recently, many states have begun using VAM scores as part of a larger system to evaluate teacher performance. In the past decade, only "core…

  20. Fitting Value-Added Models in R

    ERIC Educational Resources Information Center

    Doran, Harold C.; Lockwood, J. R.

    2006-01-01

    Value-added models of student achievement have received widespread attention in light of the current test-based accountability movement. These models use longitudinal growth modeling techniques to identify effective schools or teachers based upon the results of changes in student achievement test scores. Given their increasing popularity, this…

  1. Adding a Statistical Wrench to the "Toolbox"

    ERIC Educational Resources Information Center

    DesJardins, Stephen L.; Lindsay, Nathan K.

    2008-01-01

    This paper demonstrates a formal statistical test that can be used to help researchers make decisions about alternative statistical model specifications. This test is commonly used by researchers who would like to test whether adding new variables to a model improves the model fit. However, we demonstrate that this formal test can also be employed…

  2. "Value Added" Gauge of Teaching Probed

    ERIC Educational Resources Information Center

    Viadero, Debra

    2009-01-01

    A new study by a public and labor economist suggests that "value added" methods for determining the effectiveness of classroom teachers are built on some shaky assumptions and may be misleading. The study, due to be published in February in the "Quarterly Journal of Economics," is the first of a handful of papers now in the publishing pipeline…

  3. Double relaxation via AdS/CFT

    NASA Astrophysics Data System (ADS)

    Amiri-Sharifi, S.; Ali-Akbari, M.; Kishani-Farahani, A.; Shafie, N.

    2016-08-01

    We exploit the AdS/CFT correspondence to investigate thermalization in an N = 2 strongly coupled gauge theory including massless fundamental matter (quark). More precisely, we consider the response of a zero temperature state of the gauge theory under influence of an external electric field which leads to a time-dependent current. The holographic dual of the above set-up is given by introducing a time-dependent electric field on the probe D7-brane embedded in an AdS5 ×S5 background. In the dual gravity theory an apparent horizon forms on the brane which, according to AdS/CFT dictionary, is the counterpart of the thermalization process in the gauge theory side. We classify different functions for time-dependent electric field and study their effect on the apparent horizon formation. In the case of pulse functions, where the electric field varies from zero to zero, apart from non-equilibrium phase, we observe the formation of two separate apparent horizons on the brane. This means that the state of the gauge theory experiences two different temperature regimes during its time evolution.

  4. Imago Mundi, Imago AD, Imago ADNI

    PubMed Central

    2014-01-01

    Since the launch in 2003 of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) in the USA, ever growing, similarly oriented consortia have been organized and assembled around the world. The various accomplishments of ADNI have contributed substantially to a better understanding of the underlying physiopathology of aging and Alzheimer’s disease (AD). These accomplishments are basically predicated in the trinity of multimodality, standardization and sharing. This multimodality approach can now better identify those subjects with AD-specific traits that are more likely to present cognitive decline in the near future and that might represent the best candidates for smaller but more efficient therapeutic trials – trials that, through gained and shared knowledge, can be more focused on a specific target or a specific stage of the disease process. In summary, data generated from ADNI have helped elucidate some of the pathophysiological mechanisms underpinning aging and AD pathology, while contributing to the international effort in setting the groundwork for biomarker discovery and establishing standards for early diagnosis of AD. PMID:25478022

  5. Adding Users to the Website Design Process

    ERIC Educational Resources Information Center

    Tomeo, Megan L.

    2012-01-01

    Alden Library began redesigning its website over a year ago. Throughout the redesign process the students, faculty, and staff that make up the user base were added to the conversation by utilizing several usability test methods. This article focuses on the usability testing conducted at Alden Library and delves into future usability testing, which…

  6. The AD Nurse: Prepared to be Prepared

    ERIC Educational Resources Information Center

    Beverly, Lynne; Junker, Mary H.

    1977-01-01

    It is not enough for the new associate degree (AD) nursing graduate to know the theory and be willing to learn. She must also have some skill in providing basic nursing care. Examples of applicants, both ADNs and BSNs, are described to illustrate the nursing talent necessary to practice sensitively and effectively. (Editor/TA)

  7. Value Added School Review Field Guide

    ERIC Educational Resources Information Center

    Alberta Education, 2009

    2009-01-01

    The "Value-Added School Review (VSR)" is an analytical model designed to assist schools in identifying and addressing opportunities for school improvement. The model works best when it is focused purposefully on students and the student learning outcomes as defined in the "Guide to Education". It complements the processes described in Alberta…

  8. "Value Added" Proves Beneficial to Teacher Prep

    ERIC Educational Resources Information Center

    Sawchuk, Stephen

    2012-01-01

    The use of "value added" information appears poised to expand into the nation's teacher colleges, with more than a dozen states planning to use the technique to analyze how graduates of training programs fare in classrooms. Supporters say the data could help determine which teacher education pathways produce teachers who are at least as…

  9. Drag force in AdS/CFT

    SciTech Connect

    Gubser, Steven S.

    2006-12-15

    The AdS/CFT correspondence and a classical test string approximation are used to calculate the drag force on an external quark moving in a thermal plasma of N=4 super-Yang-Mills theory. This computation is motivated by the phenomenon of jet-quenching in relativistic heavy ion collisions.

  10. Cutting Budget Corners While Adding Value.

    ERIC Educational Resources Information Center

    Veile, Craig N.; Carpenter, Mark J.

    2000-01-01

    Discusses how one school district saved money while adding long- term value to its capital improvement project. Planning issues involving square footage requirements, quality of material to be used, and heating and cooling system selection are discussed as are concepts to increase student learning capacity for the same construction dollars. (GR)

  11. Anomaly Detection Techniques for Ad Hoc Networks

    ERIC Educational Resources Information Center

    Cai, Chaoli

    2009-01-01

    Anomaly detection is an important and indispensable aspect of any computer security mechanism. Ad hoc and mobile networks consist of a number of peer mobile nodes that are capable of communicating with each other absent a fixed infrastructure. Arbitrary node movements and lack of centralized control make them vulnerable to a wide variety of…

  12. Value-Added Analysis in Instruction

    ERIC Educational Resources Information Center

    Nicholson, Michael R.; Brown, Jeffrey R.

    2010-01-01

    Value-added data provide a viable alternative for gauging school effectiveness--one virtually free of the confounding effects of student demographics and other factors relating to student learning. How is it different from other measuring methods? It concentrates on growth, rather than attainment. This strengthens the concept and measurement of…

  13. Adding Test Generation to the Teaching Machine

    ERIC Educational Resources Information Center

    Bruce-Lockhart, Michael; Norvell, Theodore; Crescenzi, Pierluigi

    2009-01-01

    We propose an extension of the Teaching Machine project, called Quiz Generator, that allows instructors to produce assessment quizzes in the field of algorithm and data structures quite easily. This extension makes use of visualization techniques and is based on new features of the Teaching Machine that allow third-party visualizers to be added as…

  14. Protein phosphorylation systems in postmortem human brain

    SciTech Connect

    Walaas, S.I.; Perdahl-Wallace, E.; Winblad, B.; Greengard, P. )

    1989-01-01

    Protein phosphorylation systems regulated by cyclic adenosine 3',5'-monophosphate (cyclic AMP), or calcium in conjunction with calmodulin or phospholipid/diacylglycerol, have been studied by phosphorylation in vitro of particulate and soluble fractions from human postmortem brain samples. One-dimensional or two-dimensional gel electrophoretic protein separations were used for analysis. Protein phosphorylation catalyzed by cyclic AMP-dependent protein kinase was found to be highly active in both particulate and soluble preparations throughout the human CNS, with groups of both widely distributed and region-specific substrates being observed in different brain nuclei. Dopamine-innervated parts of the basal ganglia and cerebral cortex contained the phosphoproteins previously observed in rodent basal ganglia. In contrast, calcium/phospholipid-dependent and calcium/calmodulin-dependent protein phosphorylation systems were less prominent in human postmortem brain than in rodent brain, and only a few widely distributed substrates for these protein kinases were found. Protein staining indicated that postmortem proteolysis, particularly of high-molecular-mass proteins, was prominent in deeply located, subcortical regions in the human brain. Our results indicate that it is feasible to use human postmortem brain samples, when obtained under carefully controlled conditions, for qualitative studies on brain protein phosphorylation. Such studies should be of value in studies on human neurological and/or psychiatric disorders.

  15. HRT and its effect on normal ageing of the brain and dementia

    PubMed Central

    Compton, Jacqueline; van Amelsvoort, Therese; Murphy, Declan

    2001-01-01

    There are significant gender differences in human brain disease. For example, females are significantly more likely to suffer from Alzheimer's disease (AD) than men (even after correcting for differences in life expectancy), and females on hormone replacement therapy (HRT) are significantly less likely to suffer from Alzheimer's disease than women who do not take HRT. However the neurobiological basis to these differences in clinical brain disease were unknown until relatively recently. In this review we will discuss results of studies that show; (i) gender differences in human brain disease are most likely to be explained by gender differences in brain development and ageing; (ii) sex steroids have a significant effect on the brain; (iii) sex steroids are crucial to the development and ageing of brain regions affected in age-related brain diseases (for example AD); (iv) sex steroids interact with neuronal networks and chemical systems at many different levels; (v) sex steroids affect cognitive function in elderly women. Thus, the current literature supports the hypothesis that sex steroids can modulate brain ageing, and this provides a neurobiological explanation for the significantly higher prevalence of AD in females who do not take HRT, and may lead to new treatment approaches for age-related brain disease including AD. PMID:11736875

  16. Regulation of brain aquaporins.

    PubMed

    Zelenina, Marina

    2010-11-01

    Three aquaporins are expressed in the brain. AQP4, the predominant brain water channel, is expressed in astrocyte endfeet facing brain capillaries, perisynaptic spaces, and nodes of Ranvier. It is implicated in brain edema formation and resolution. It is also believed to assist clearance of K(+) released during neuronal activity. AQP1 is expressed in epithelial cells of choroid plexus and is implicated in cerebrospinal fluid formation. AQP9, which has been reported to be present in astrocytes and in subpopulations of neurons, is implicated in the brain energy metabolism. All three brain AQPs are strongly upregulated in brain tumors and in injured brain tissue. Water and solute transport via AQPs depends on concentration gradients across the membrane, but the magnitude of the transport is to a large extent determined by the single channel permeability of AQPs and by their abundance in the cell membrane. The future therapies will have to address not only the forces driving the water and solute transport (e.g. as mannitol infusion does in the treatment of brain edema), but also the regulation of AQPs, which provide the means for water entry to the brain, for water exit from the brain, and for redistribution of water and solutes within the brain compartments. This review summarizes the data concerning structure, permeability, role in the brain, short-term and long-term regulation of the three AQPs.

  17. Holographic Hydrodynamics with Baryon Chemical Potential for Charged AdS Black Hole

    SciTech Connect

    Takeuchi, Shingo

    2009-12-15

    We work out the decoupling problem and hydrodynamic analysis for the sound mode in charged AdS black hole and calculate the sound velocity, the charge susceptibility and the electrical conductivity. We find that Einstein relation among the conductivity, the diffusion constant and the susceptibility holds exactly.

  18. Avoiding Ad Avoidance: Factors Affecting the Perception of Online Banner Ads

    ERIC Educational Resources Information Center

    Portnoy, Felix

    2012-01-01

    This dissertation examined the effect of search type, ad saliency, and ad repetition on the perception of online banner advertisements. In the first study, 48 student participants conducted simulated search tasks using mixed factorial design where search type (known-item vs. exploratory) was manipulated within-subject and the banner saliency level…

  19. Designing added functions in engineered cementitious composites

    NASA Astrophysics Data System (ADS)

    Yang, En-Hua

    In this dissertation, a new and systematic material design approach is developed for ECC with added functions through material microstructures linkage to composite macroscopic behavior. The thesis research embodies theoretical development by building on previous ECC micromechanical models, and experimental investigations into three specific new versions of ECC with added functions aimed at addressing societal demands of our built infrastructure. Specifically, the theoretical study includes three important ECC modeling elements: Steady-state crack propagation analyses and simulation, predictive accuracy of the fiber bridging constitutive model, and development of the rate-dependent strain-hardening criteria. The first element establishes the steady-state cracking criterion as a fundamental requirement for multiple cracking behavior in brittle matrix composites. The second element improves the accuracy of crack-width prediction in ECC. The third element establishes the micromechanics basis for impact-resistant ECC design. Three new ECCs with added functions were developed and experimentally verified in this thesis research through the enhanced theoretical framework. A green ECC incorporating a large volume of industrial waste was demonstrated to possess reduced crack width and drying shrinkage. The self-healing ECC designed with tight crack width was demonstrated to recover transport and mechanical properties after microcrack damage when exposed to wet and dry cycles. The impact-resistant ECC was demonstrated to retain tensile ductility with increased strength under moderately high strain-rate loading. These new versions of ECC with added functions are expected to contribute greatly to enhancing the sustainability, durability, and safety of civil infrastructure built with ECC. This research establishes the effectiveness of micromechanics-based design and material ingredient tailoring for ECC with added new attributes but without losing its basic tensile ductile

  20. Understanding brain networks and brain organization

    PubMed Central

    Pessoa, Luiz

    2014-01-01

    What is the relationship between brain and behavior? The answer to this question necessitates characterizing the mapping between structure and function. The aim of this paper is to discuss broad issues surrounding the link between structure and function in the brain that will motivate a network perspective to understanding this question. As others in the past, I argue that a network perspective should supplant the common strategy of understanding the brain in terms of individual regions. Whereas this perspective is needed for a fuller characterization of the mind-brain, it should not be viewed as panacea. For one, the challenges posed by the many-to-many mapping between regions and functions is not dissolved by the network perspective. Although the problem is ameliorated, one should not anticipate a one-to-one mapping when the network approach is adopted. Furthermore, decomposition of the brain network in terms of meaningful clusters of regions, such as the ones generated by community-finding algorithms, does not by itself reveal “true” subnetworks. Given the hierarchical and multi-relational relationship between regions, multiple decompositions will offer different “slices” of a broader landscape of networks within the brain. Finally, I described how the function of brain regions can be characterized in a multidimensional manner via the idea of diversity profiles. The concept can also be used to describe the way different brain regions participate in networks. PMID:24819881

  1. Dissociable brain biomarkers of fluid intelligence.

    PubMed

    Paul, Erick J; Larsen, Ryan J; Nikolaidis, Aki; Ward, Nathan; Hillman, Charles H; Cohen, Neal J; Kramer, Arthur F; Barbey, Aron K

    2016-08-15

    Cognitive neuroscience has long sought to understand the biological foundations of human intelligence. Decades of research have revealed that general intelligence is correlated with two brain-based biomarkers: the concentration of the brain biochemical N-acetyl aspartate (NAA) measured by proton magnetic resonance spectroscopy (MRS) and total brain volume measured using structural MR imaging (MRI). However, the relative contribution of these biomarkers in predicting performance on core facets of human intelligence remains to be well characterized. In the present study, we sought to elucidate the role of NAA and brain volume in predicting fluid intelligence (Gf). Three canonical tests of Gf (BOMAT, Number Series, and Letter Sets) and three working memory tasks (Reading, Rotation, and Symmetry span tasks) were administered to a large sample of healthy adults (n=211). We conducted exploratory factor analysis to investigate the factor structure underlying Gf independent from working memory and observed two Gf components (verbal/spatial and quantitative reasoning) and one working memory component. Our findings revealed a dissociation between two brain biomarkers of Gf (controlling for age and sex): NAA concentration correlated with verbal/spatial reasoning, whereas brain volume correlated with quantitative reasoning and working memory. A follow-up analysis revealed that this pattern of findings is observed for males and females when analyzed separately. Our results provide novel evidence that distinct brain biomarkers are associated with specific facets of human intelligence, demonstrating that NAA and brain volume are independent predictors of verbal/spatial and quantitative facets of Gf. PMID:27184204

  2. Differential hippocampal shapes in posterior cortical atrophy patients: A comparison with control and typical AD subjects

    PubMed Central

    Macdonald, Kate E.; Leung, Kelvin K.; Young, Jonathan; Pepple, Tracey; Lehmann, Manja; Zuluaga, Maria A.; Cardoso, M. Jorge; Schott, Jonathan M.; Ourselin, Sebastien; Crutch, Sebastian; Fox, Nick C.; Barnes, Josephine

    2015-01-01

    Abstract Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterized by predominant visual deficits and parieto‐occipital atrophy, and is typically associated with Alzheimer's disease (AD) pathology. In AD, assessment of hippocampal atrophy is widely used in diagnosis, research, and clinical trials; its utility in PCA remains unclear. Given the posterior emphasis of PCA, we hypothesized that hippocampal shape measures may give additional group differentiation information compared with whole‐hippocampal volume assessments. We investigated hippocampal volume and shape in subjects with PCA (n = 47), typical AD (n = 29), and controls (n = 48). Hippocampi were outlined on MRI scans and their 3D meshes were generated. We compared hippocampal volume and shape between disease groups. Mean adjusted hippocampal volumes were ∼8% smaller in PCA subjects (P < 0.001) and ∼22% smaller in tAD subject (P < 0.001) compared with controls. Significant inward deformations in the superior hippocampal tail were observed in PCA compared with controls even after adjustment for hippocampal volume. Inward deformations in large areas of the hippocampus were seen in tAD subjects compared with controls and PCA subjects, but only localized shape differences remained after adjusting for hippocampal volume. The shape differences observed, even allowing for volume differences, suggest that PCA and tAD are each associated with different patterns of hippocampal tissue loss that may contribute to the differential range and extent of episodic memory dysfunction in the two groups. Hum Brain Mapp 36:5123–5136, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. PMID:26461053

  3. Hairy black holes in AdS5 × S 5

    NASA Astrophysics Data System (ADS)

    Markeviciute, Julija; Santos, Jorge E.

    2016-06-01

    We use numerical methods to exhaustively study a novel family of hairy black hole solutions in AdS5. These solutions can be uplifted to solutions of type IIB supergravity with AdS5 × S 5 asymptotics and are thus expected to play an important role in our understanding of AdS/CFT. We find an intricate phase diagram, with the aforementioned family of hairy black hole solutions branching from the Reissner-Nordström black hole at the onset of the superradiance instability. We analyse black holes with spherical and planar horizon topology and explain how they connect in the phase diagram. Finally, we detail their global and local thermodynamic stability across several ensembles.

  4. Left Brain, Right Brain: Facts and Fantasies

    PubMed Central

    Corballis, Michael C.

    2014-01-01

    Summary Handedness and brain asymmetry are widely regarded as unique to humans, and associated with complementary functions such as a left-brain specialization for language and logic and a right-brain specialization for creativity and intuition. In fact, asymmetries are widespread among animals, and support the gradual evolution of asymmetrical functions such as language and tool use. Handedness and brain asymmetry are inborn and under partial genetic control, although the gene or genes responsible are not well established. Cognitive and emotional difficulties are sometimes associated with departures from the “norm” of right-handedness and left-brain language dominance, more often with the absence of these asymmetries than their reversal. PMID:24465175

  5. Left brain, right brain: facts and fantasies.

    PubMed

    Corballis, Michael C

    2014-01-01

    Handedness and brain asymmetry are widely regarded as unique to humans, and associated with complementary functions such as a left-brain specialization for language and logic and a right-brain specialization for creativity and intuition. In fact, asymmetries are widespread among animals, and support the gradual evolution of asymmetrical functions such as language and tool use. Handedness and brain asymmetry are inborn and under partial genetic control, although the gene or genes responsible are not well established. Cognitive and emotional difficulties are sometimes associated with departures from the "norm" of right-handedness and left-brain language dominance, more often with the absence of these asymmetries than their reversal. PMID:24465175

  6. Modulating Brain Oscillations to Drive Brain Function

    PubMed Central

    Thut, Gregor

    2014-01-01

    Do neuronal oscillations play a causal role in brain function? In a study in this issue of PLOS Biology, Helfrich and colleagues address this long-standing question by attempting to drive brain oscillations using transcranial electrical current stimulation. Remarkably, they were able to manipulate visual perception by forcing brain oscillations of the left and right visual hemispheres into synchrony using oscillatory currents over both hemispheres. Under this condition, human observers more often perceived an inherently ambiguous visual stimulus in one of its perceptual instantiations. These findings shed light on the mechanisms underlying neuronal computation. They show that it is the neuronal oscillations that drive the visual experience, not the experience driving the oscillations. And they indicate that synchronized oscillatory activity groups brain areas into functional networks. This points to new ways for controlled experimental and possibly also clinical interventions for the study and modulation of brain oscillations and associated functions. PMID:25549340

  7. Brain tumor - primary - adults

    MedlinePlus

    ... tumor, relieve symptoms, and improve brain function or comfort. Surgery is often needed for most primary brain ... and pressure Anticonvulsants to reduce seizures Pain medicines Comfort measures, safety measures, physical therapy, and occupational therapy ...

  8. Brain tumor - children

    MedlinePlus

    ... symptoms, and improve brain function or the child's comfort. Surgery is needed for most primary brain tumors. ... Anticonvulsants to reduce or prevent seizures Pain medicines Comfort measures, safety measures, physical therapy, occupational therapy, and ...

  9. Brain Tumor Statistics

    MedlinePlus

    ... facts and statistics here include brain and central nervous system tumors (including spinal cord, pituitary and pineal gland ... U.S. living with a primary brain and central nervous system tumor. This year, nearly 17,000 people will ...

  10. Children's Brain Tumor Foundation

    MedlinePlus

    ... CBTF Justin's Hope Fund Grant Recipients Grants Children’s Brain Tumor Foundation, A non-profit organization, was founded ... and the long term outlook for children with brain and spinal cord tumors through research, support, education, ...

  11. Genetic Brain Disorders

    MedlinePlus

    A genetic brain disorder is caused by a variation or a mutation in a gene. A variation is a different form ... mutation is a change in a gene. Genetic brain disorders affect the development and function of the ...

  12. Childhood Brain Tumors

    MedlinePlus

    Brain tumors are abnormal growths inside the skull. They are among the most common types of childhood ... still be serious. Malignant tumors are cancerous. Childhood brain and spinal cord tumors can cause headaches and ...

  13. Pediatric Brain Tumor Foundation

    MedlinePlus

    ... you insights into your child's treatment. LEARN MORE Brain tumors and their treatment can be deadly so ... Cancer Foundation joins the PBTF Read more >> Pediatric Brain Tumor Foundation 302 Ridgefield Court, Asheville, NC 28806 ...

  14. Brain aneurysm repair

    MedlinePlus

    ... aneurysm repair; Dissecting aneurysm repair; Endovascular aneurysm repair - brain; Subarachnoid hemorrhage - aneurysm ... Your scalp, skull, and the coverings of the brain are opened. A metal clip is placed at ...

  15. American Brain Tumor Association

    MedlinePlus

    ... in the Ear Canals Read More ABTA News October 5, 2016 Largest American Brain Tumor Association Team Running in Bank of America Chicago Marathon Sunday, October 9 September 21, 2016 American Brain Tumor Association Awards 16 Grants to Support ...

  16. Anatomy of the Brain

    MedlinePlus

    ... our existence. It controls our personality, thoughts, memory, intelligence, speech and understanding, emotions, senses, and basic body functions, as well as how we function in our environment. The diagrams below show brain anatomy, or the various parts of the brain, ...

  17. Biophysics: Unfolding the brain

    NASA Astrophysics Data System (ADS)

    Kuhl, Ellen

    2016-06-01

    The folded surface of the human brain, although striking, continues to evade understanding. Experiments with swelling gels now fuel the notion that brain folding is modulated by physical forces, and not by genetic, biological or chemical events alone.

  18. Brain natriutetic peptide test

    MedlinePlus

    ... medlineplus.gov/ency/article/007509.htm Brain natriuretic peptide test To use the sharing features on this page, please enable JavaScript. Brain natriuretic peptide (BNP) test is a blood test that measures ...

  19. Oral branched-chain amino acid supplements that reduce brain serotonin during exercise in rats also lower brain catecholamines.

    PubMed

    Choi, Sujean; Disilvio, Briana; Fernstrom, Madelyn H; Fernstrom, John D

    2013-11-01

    Exercise raises brain serotonin release and is postulated to cause fatigue in athletes; ingestion of branched-chain amino acids (BCAA), by competitively inhibiting tryptophan transport into brain, lowers brain tryptophan uptake and serotonin synthesis and release in rats, and reputedly in humans prevents exercise-induced increases in serotonin and fatigue. This latter effect in humans is disputed. But BCAA also competitively inhibit tyrosine uptake into brain, and thus catecholamine synthesis and release. Since increasing brain catecholamines enhances physical performance, BCAA ingestion could lower catecholamines, reduce performance and thus negate any serotonin-linked benefit. We therefore examined in rats whether BCAA would reduce both brain tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis. Sedentary and exercising rats received BCAA or vehicle orally; tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis rates were measured 1 h later in brain. BCAA reduced brain tryptophan and tyrosine concentrations, and serotonin and catecholamine synthesis. These reductions in tyrosine concentrations and catecholamine synthesis, but not tryptophan or serotonin synthesis, could be prevented by co-administering tyrosine with BCAA. Complete essential amino acid mixtures, used to maintain or build muscle mass, were also studied, and produced different effects on brain tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis. Since pharmacologically increasing brain catecholamine function improves physical performance, the finding that BCAA reduce catecholamine synthesis may explain why this treatment does not enhance physical performance in humans, despite reducing serotonin synthesis. If so, adding tyrosine to BCAA supplements might allow a positive action on performance to emerge.

  20. AdS/CFT connection between Boltzmann and Einstein equations: Kinetic theory and pure gravity in AdS space

    SciTech Connect

    Iyer, Ramakrishnan; Mukhopadhyay, Ayan

    2010-04-15

    The AdS/CFT correspondence defines a sector with universal strongly coupled dynamics in the field theory as the dual of pure gravity in AdS described by Einstein's equation with a negative cosmological constant. We explain here, from the field-theoretic viewpoint how the dynamics in this sector gets determined by the expectation value of the energy-momentum tensor alone. We first show that the Boltzmann equation has very special solutions which could be functionally completely determined in terms of the energy-momentum tensor alone. We call these solutions conservative solutions. We indicate why conservative solutions should also exist when we refine this kinetic description to go closer to the exact microscopic theory or even move away from the regime of weak coupling so that no kinetic description could be employed. We argue that these conservative solutions form the universal sector dual to pure gravity at strong coupling and large N. Based on this observation, we propose a regularity condition on the energy-momentum tensor so that the dual solution in pure gravity has a smooth future horizon. We also study if irreversibility emerges only at long time scales of observation, unlike the case of the Boltzmann equation.

  1. Can Ketones Help Rescue Brain Fuel Supply in Later Life? Implications for Cognitive Health during Aging and the Treatment of Alzheimer’s Disease

    PubMed Central

    Cunnane, Stephen C.; Courchesne-Loyer, Alexandre; Vandenberghe, Camille; St-Pierre, Valérie; Fortier, Mélanie; Hennebelle, Marie; Croteau, Etienne; Bocti, Christian; Fulop, Tamas; Castellano, Christian-Alexandre

    2016-01-01

    We propose that brain energy deficit is an important pre-symptomatic feature of Alzheimer’s disease (AD) that requires closer attention in the development of AD therapeutics. Our rationale is fourfold: (i) Glucose uptake is lower in the frontal cortex of people >65 years-old despite cognitive scores that are normal for age. (ii) The regional deficit in brain glucose uptake is present in adults <40 years-old who have genetic or lifestyle risk factors for AD but in whom cognitive decline has not yet started. Examples include young adult carriers of presenilin-1 or apolipoprotein E4, and young adults with mild insulin resistance or with a maternal family history of AD. (iii) Regional brain glucose uptake is impaired in AD and mild cognitive impairment (MCI), but brain uptake of ketones (beta-hydroxybutyrate and acetoacetate), remains the same in AD and MCI as in cognitively healthy age-matched controls. These observations point to a brain fuel deficit which appears to be specific to glucose, precedes cognitive decline associated with AD, and becomes more severe as MCI progresses toward AD. Since glucose is the brain’s main fuel, we suggest that gradual brain glucose exhaustion is contributing significantly to the onset or progression of AD. (iv) Interventions that raise ketone availability to the brain improve cognitive outcomes in both MCI and AD as well as in acute experimental hypoglycemia. Ketones are the brain’s main alternative fuel to glucose and brain ketone uptake is still normal in MCI and in early AD, which would help explain why ketogenic interventions improve some cognitive outcomes in MCI and AD. We suggest that the brain energy deficit needs to be overcome in order to successfully develop more effective therapeutics for AD. At present, oral ketogenic supplements are the most promising means of achieving this goal. PMID:27458340

  2. NASA Robot Brain Surgeon

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Mechanical Engineer Michael Guerrero works on the Robot Brain Surgeon testbed in the NeuroEngineering Group at the Ames Research Center, Moffett Field, California. Principal investigator Dr. Robert W. Mah states that potentially the simple robot will be able to feel brain structures better than any human surgeon, making slow, very precise movements during an operation. The brain surgery robot that may give surgeons finer control of surgical instruments during delicate brain operations is still under development.

  3. Neuromythology of Einstein's brain.

    PubMed

    Hines, Terence

    2014-07-01

    The idea that the brain of the great physicist Albert Einstein is different from "average" brains in both cellular structure and external shape is widespread. This belief is based on several studies examining Einstein's brain both histologically and morphologically. This paper reviews these studies and finds them wanting. Their results do not, in fact, provide support for the claim that the structure of Einstein's brain reflects his intellectual abilities.

  4. Effect of intellectual enrichment on AD biomarker trajectories

    PubMed Central

    Lesnick, Timothy G.; Przybelski, Scott A.; Knopman, David S.; Machulda, Mary; Lowe, Val J.; Mielke, Michelle M.; Roberts, Rosebud O.; Gunter, Jeffrey L.; Senjem, Matthew L.; Geda, Yonas E.; Rocca, Walter A.; Petersen, Ronald C.; Jack, Clifford R.

    2016-01-01

    Objective: To investigate the effect of age, sex, APOE4 genotype, and lifestyle enrichment (education/occupation, midlife cognitive activity, and midlife physical activity) on Alzheimer disease (AD) biomarker trajectories using longitudinal imaging data (brain β-amyloid load via Pittsburgh compound B PET and neurodegeneration via 18fluorodeoxyglucose (FDG) PET and structural MRI) in an elderly population without dementia. Methods: In the population-based longitudinal Mayo Clinic Study of Aging, we studied 393 participants without dementia (340 clinically normal, 53 mild cognitive impairment; 70 years and older) who had cognitive and physical activity measures and at least 2 visits with imaging biomarkers. We dichotomized participants into high (≥14 years) and low (<14 years) education levels using the median. For the entire cohort and the 2 education strata, we built linear mixed models to investigate the effect of the predictors on each of the biomarker outcomes. Results: Age was associated with amyloid and neurodegeneration trajectories; APOE4 status appears to influence only the amyloid and FDG trajectories but not hippocampal volume trajectory. In the high-education stratum, high midlife cognitive activity was associated with lower amyloid deposition in APOE4 carriers. APOE4 status was associated with lower FDG uptake in the entire cohort and in participants with lower education but not the high-education cohort. Conclusions: There were minimal effects of lifestyle enrichment on AD biomarker trajectories (specifically rates). Lifetime intellectual enrichment (high education, high midlife cognitive activity) is associated with lower amyloid in APOE4 carriers. High education is protective from the APOE4 effect on FDG metabolism. Differing education levels may explain the conflicting results seen in the literature. PMID:26911640

  5. Aligning brains and minds

    PubMed Central

    Tong, Frank

    2012-01-01

    In this issue of Neuron, Haxby and colleagues describe a new method for aligning functional brain activity patterns across participants. Their study demonstrates that objects are similarly represented across different brains, allowing for reliable classification of one person’s brain activity based on another’s. PMID:22017984

  6. Our Amazing Brains

    ERIC Educational Resources Information Center

    Bath, Howard

    2005-01-01

    This article begins a regular series on how brain research can help us understand young people and ourselves as well. The intent is to alert the reader to important information from recent research on the brain. This initial installment explores the concept of the triune brain, a term coined by neuroscientist Paul MacLean. This refers to three…

  7. Brain and Addiction

    MedlinePlus

    ... brain. View Online Download PDF The Awesomely Evolved Human Brain Published: September 01, 2013 The brain is an ... mark of the U.S. Department of Health and Human Services (HHS). The National Drug & Alcohol Facts Week design mark, and associated trade dress are registered ... close

  8. Build-a-brain.

    PubMed

    Chambers, Stuart M; Tchieu, Jason; Studer, Lorenz

    2013-10-01

    A major barrier in understanding nervous system development is modeling the cellular interactions that form the human brain. Recently, in the journal Nature, Lancaster et al. (2013) established a protocol for culturing pluripotent stem cell (PSC)-derived "cerebral organoids" that mimics the developing human brain's cellular organization, segregates into distinct brain regions, and models microcephaly. PMID:24094317

  9. Brain and Spinal Tumors

    MedlinePlus

    ... Awards Enhancing Diversity Find People About NINDS NINDS Brain and Spinal Tumors Information Page Synonym(s): Spinal Cord ... en Español Additional resources from MedlinePlus What are Brain and Spinal Tumors? Tumors of the brain and ...

  10. Brain Research and Learning.

    ERIC Educational Resources Information Center

    Claycomb, Mary

    Current research on brain activity has many implications for educators. The triune brain concept and the left and right hemisphere concepts are among the many complex theories evolving from experimentation and observation. The triune brain concept suggests that the human forebrain has expanded while retaining three structurally unique formations…

  11. Brain Structure and Development.

    ERIC Educational Resources Information Center

    Teyler, T.J.; Chiaia, N.

    1983-01-01

    Considers basic biology of brain, what is known of how it operates, and something of how it develops. Discusses properties of neurons and specialized regions of the brain in linguistic and higher order processing skills, as well as genetic and environmental influences on brain development. (CMG)

  12. Aneurysm in the brain

    MedlinePlus

    ... aneurysm may be found when an MRI or CT scan of the brain is done for another reason. A brain aneurysm ... and determine the cause of bleeding in the brain: Cerebral angiography or spiral CT scan angiography of the head to show the location ...

  13. Traumatic Brain Injury

    MedlinePlus

    ... a concussion may feel dazed and may lose vision or balance for a while after the injury A brain contusion is a bruise of the brain. This ... consciousness Headache Confusion Feeling dizzy or lightheaded Blurry vision ... or severe traumatic brain injury include all of the symptoms listed above ...

  14. Altered brain response for semantic knowledge in Alzheimer's disease.

    PubMed

    Wierenga, Christina E; Stricker, Nikki H; McCauley, Ashley; Simmons, Alan; Jak, Amy J; Chang, Yu-Ling; Nation, Daniel A; Bangen, Katherine J; Salmon, David P; Bondi, Mark W

    2011-02-01

    Word retrieval deficits are common in Alzheimer's disease (AD) and are thought to reflect a degradation of semantic memory. Yet, the nature of semantic deterioration in AD and the underlying neural correlates of these semantic memory changes remain largely unknown. We examined the semantic memory impairment in AD by investigating the neural correlates of category knowledge (e.g., living vs. nonliving) and featural processing (global vs. local visual information). During event-related fMRI, 10 adults diagnosed with mild AD and 22 cognitively normal (CN) older adults named aloud items from three categories for which processing of specific visual features has previously been dissociated from categorical features. Results showed widespread group differences in the categorical representation of semantic knowledge in several language-related brain areas. For example, the right inferior frontal gyrus showed selective brain response for nonliving items in the CN group but living items in the AD group. Additionally, the AD group showed increased brain response for word retrieval irrespective of category in Broca's homologue in the right hemisphere and rostral cingulate cortex bilaterally, which suggests greater recruitment of frontally mediated neural compensatory mechanisms in the face of semantic alteration. PMID:21163275

  15. Primary lymphoma of the brain

    MedlinePlus

    Brain lymphoma; Cerebral lymphoma; Primary lymphoma of the central nervous system; Lymphoma - brain ... The cause of primary brain lymphoma is not known. People with a weakened immune system are at high risk for primary lymphoma of the brain. ...

  16. Synchrotron FTIR microspectroscopy of Alzheimer's diseased brain tissue at the SRC beamline

    NASA Astrophysics Data System (ADS)

    Bromberg, Pam S.; Gough, Kathleen M.; Ogg, Mandy; Del Bigio, M. R.; Julian, Robert

    1999-10-01

    Alzheimer's Disease is a neurodegenerative disorder marked by progressive cognitive decline. AD presents with many of the same clinical symptoms as senile dementia, but the diagnosis of AD must be confirmed by post-mortem examination of the morphological and histopathological features of the brain. The two classical lesions found in the cortical and hippocampal regions of the brain are the (beta) -amyloid- bearing neuritic plaques and the intraneuronal neurofibrillary tangles.

  17. The levels of soluble versus insoluble brain Abeta distinguish Alzheimer's disease from normal and pathologic aging.

    PubMed

    Wang, J; Dickson, D W; Trojanowski, J Q; Lee, V M

    1999-08-01

    The abundance and solubility of Abeta peptides are critical determinants of amyloidosis in Alzheimer's disease (AD). Hence, we compared levels of total soluble, insoluble, and total Abeta1-40 and Abeta1-42 in AD brains with those in age-matched normal and pathologic aging brains using a sandwich enzyme-linked immunosorbent assay (ELISA). Since the measurement of Abeta1-40 and Abeta1-42 depends critically on the specificity of the monoclonal antibodies used in the sandwich ELISA, we first demonstrated that each assay is specific for Abeta1-40 or Abeta1-42 and the levels of these peptides are not affected by the amyloid precursor protein in the brain extracts. Thus, this sandwich ELISA enabled us to show that the average levels of total cortical soluble and insoluble Abeta1-40 and Abeta1-42 were highest in AD, lowest in normal aging, and intermediate in pathologic aging. Remarkably, the average levels of insoluble Abeta1-40 were increased 20-fold while the average levels of insoluble Abeta1-42 were increased only 2-fold in the AD brains compared to pathologic aging brains. Further, the soluble pools of Abeta1-40 and Abeta1-42 were the largest fractions of total Abeta in the normal brain (i.e., 50 and 23%, respectively), but they were the smallest in the AD brain (i.e., 2.7 and 0.7%, respectively) and intermediate (i.e., 8 and 0.8%, respectively) in pathologic aging brains. Thus, our data suggest that pathologic aging is a transition state between normal aging and AD. More importantly, our findings imply that a progressive shift of brain Abeta1-40 and Abeta1-42 from soluble to insoluble pools and a profound increase in the levels of insoluble Abeta1-40 plays mechanistic roles in the onset and/or progression of AD.

  18. Brain Injury Alters Volatile Metabolome.

    PubMed

    Kimball, Bruce A; Cohen, Akiva S; Gordon, Amy R; Opiekun, Maryanne; Martin, Talia; Elkind, Jaclynn; Lundström, Johan N; Beauchamp, Gary K

    2016-06-01

    Chemical signals arising from body secretions and excretions communicate information about health status as have been reported in a range of animal models of disease. A potential common pathway for diseases to alter chemical signals is via activation of immune function-which is known to be intimately involved in modulation of chemical signals in several species. Based on our prior findings that both immunization and inflammation alter volatile body odors, we hypothesized that injury accompanied by inflammation might correspondingly modify the volatile metabolome to create a signature endophenotype. In particular, we investigated alteration of the volatile metabolome as a result of traumatic brain injury. Here, we demonstrate that mice could be trained in a behavioral assay to discriminate mouse models subjected to lateral fluid percussion injury from appropriate surgical sham controls on the basis of volatile urinary metabolites. Chemical analyses of the urine samples similarly demonstrated that brain injury altered urine volatile profiles. Behavioral and chemical analyses further indicated that alteration of the volatile metabolome induced by brain injury and alteration resulting from lipopolysaccharide-associated inflammation were not synonymous. Monitoring of alterations in the volatile metabolome may be a useful tool for rapid brain trauma diagnosis and for monitoring recovery. PMID:26926034

  19. Autoantibodies Profile in Matching CSF and Serum from AD and aMCI patients: Potential Pathogenic Role and Link to Oxidative Damage.

    PubMed

    Di Domenico, Fabio; Pupo, Gilda; Giraldo, Esther; Lloret, Ana; Badia, Mari-Carmen; Schinina, Maria Eugenia; Giorgi, Alessandra; Butterfield, D Allan; Vina, Jose; Perluigi, Marzia

    2016-01-01

    Alzheimer disease (AD) is the most common form of dementia among the elderly and is characterized by progressive loss of memory and cognition. Amyloid-ß-peptide (Aß) forms senile plaques, which, together with hyperphosphorylated tau-based neurofibrillary tangles, are the hallmarks of AD neuropathology. Evidence support the involvement of immune system in AD progression and current concepts regarding its pathogenesis include the participation of inflammatory and autoimmune components in the neurodegenerative process. Pathologically, immune system components have been detected in the brain, cerebrospinal fluid (CSF) and in serum of AD subjects and their trend of variation correlates with disease progression. However, patients with AD present significantly lower levels of antibody immunoreactivity against Aß in serum and CSF than healthy controls suggesting that a depletion of such patrolling system is involved in the deposition of toxic aggregates in AD. Within this frame, incomplete and often controversial results are reported about CNS immune/ autoimmune responses during AD, and a better comprehension of such processes is needed. Our research will aim to shed light on the nature and potential role of autoantibodies in CSF and serum from AD and amnestic mild cognitive impairment (aMCI) patients compared to healthy subjects by using an immunoproteomics approach. Our method allows recognition of natural occurring antibodies by the identification of brain antigen targeted by human IgGs. Overall our data reveal that the alterations of autoantibodies profile both in CSF and serum follow disease staging and progression. However, we demonstrate a fair overlap between CSF and serum suggesting the existence of different immunogenic events. Interestingly, CSF autoantibodies recognized, among others, key players of energy metabolic pathway, including glycolysis and TCA cycle, found oxidatively modified in AD brain studies. These data suggest a potential casual sequence

  20. Tau elevations in the brain extracellular space correlate with reduced amyloid-β levels and predict adverse clinical outcomes after severe traumatic brain injury.

    PubMed

    Magnoni, Sandra; Esparza, Thomas J; Conte, Valeria; Carbonara, Marco; Carrabba, Giorgio; Holtzman, David M; Zipfel, Greg J; Stocchetti, Nino; Brody, David L

    2012-04-01

    Axonal injury is believed to be a major determinant of adverse outcomes following traumatic brain injury. However, it has been difficult to assess acutely the severity of axonal injury in human traumatic brain injury patients. We hypothesized that microdialysis-based measurements of the brain extracellular fluid levels of tau and neurofilament light chain, two low molecular weight axonal proteins, could be helpful in this regard. To test this hypothesis, 100 kDa cut-off microdialysis catheters were placed in 16 patients with severe traumatic brain injury at two neurological/neurosurgical intensive care units. Tau levels in the microdialysis samples were highest early and fell over time in all patients. Initial tau levels were >3-fold higher in patients with microdialysis catheters placed in pericontusional regions than in patients in whom catheters were placed in normal-appearing right frontal lobe tissue (P = 0.005). Tau levels and neurofilament light-chain levels were positively correlated (r = 0.6, P = 0.013). Neurofilament light-chain levels were also higher in patients with pericontusional catheters (P = 0.04). Interestingly, initial tau levels were inversely correlated with initial amyloid-β levels measured in the same samples (r = -0.87, P = 0.000023). This could be due to reduced synaptic activity in areas with substantial axonal injury, as amyloid-β release is closely coupled with synaptic activity. Importantly, high initial tau levels correlated with worse clinical outcomes, as assessed using the Glasgow Outcome Scale 6 months after injury (r = -0.6, P = 0.018). Taken together, our data add support for the hypothesis that axonal injury may be related to long-term impairments following traumatic brain injury. Microdialysis-based measurement of tau levels in the brain extracellular space may be a useful way to assess the severity of axonal injury acutely in the intensive care unit. Further studies with larger numbers of