A variety of measurements have been individually linked to decline in mild cognitive impairment (MCI), but the identification of optimal markers for predicting disease progression remains unresolved. ...The goal of this study was to evaluate the prognostic ability of genetic, CSF, neuroimaging, and cognitive measurements obtained in the same participants.
APOE epsilon4 allele frequency, CSF proteins (Abeta(1-42), total tau, hyperphosphorylated tau p-tau(181p)), glucose metabolism (FDG-PET), hippocampal volume, and episodic memory performance were evaluated at baseline in patients with amnestic MCI (n = 85), using data from a large multisite study (Alzheimer's Disease Neuroimaging Initiative). Patients were classified as normal or abnormal on each predictor variable based on externally derived cutoffs, and then variables were evaluated as predictors of subsequent conversion to Alzheimer disease (AD) and cognitive decline (Alzheimer's Disease Assessment Scale-Cognitive Subscale) during a variable follow-up period (1.9 +/- 0.4 years).
Patients with MCI converted to AD at an annual rate of 17.2%. Subjects with MCI who had abnormal results on both FDG-PET and episodic memory were 11.7 times more likely to convert to AD than subjects who had normal results on both measures (p <or= 0.02). In addition, the CSF ratio p-tau(181p)/Abeta(1-42) (beta = 1.10 +/- 0.53; p = 0.04) and, marginally, FDG-PET predicted cognitive decline.
Baseline FDG-PET and episodic memory predict conversion to AD, whereas p-tau(181p)/Abeta(1-42) and, marginally, FDG-PET predict longitudinal cognitive decline. Complementary information provided by these biomarkers may aid in future selection of patients for clinical trials or identification of patients likely to benefit from a therapeutic intervention.
The Askaryan Radio Array (ARA) is an ultrahigh energy (UHE, > 1017 eV) neutrino detector designed to observe neutrinos by searching for the radio waves emitted by the relativistic products of ...neutrino-nucleon interactions in Antarctic ice. In this paper, we present constraints on the diffuse flux of ultrahigh energy neutrinos between 1016 and 1021 eV resulting from a search for neutrinos in two complementary analyses, both analyzing four years of data (2013–2016) from the two deep stations (A2, A3) operating at that time. We place a 90% CL upper limit on the diffuse all flavor neutrino flux at 1018 eV of EF(E) = 5.6 × 10−16 cm−2 s−1 sr−1. This analysis includes four times the exposure of the previous ARA result and represents approximately 1 / 5 th the exposure expected from operating ARA until the end of 2022.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
Although β-amyloid (Aβ) plaques are a primary diagnostic criterion for Alzheimer's disease, this pathology is commonly observed in the brains of non-demented older individuals. To explore the ...importance of this pathology in the absence of dementia, we compared levels of amyloid deposition (via ‘Pittsburgh Compound-B’ (PIB) positron emission tomography (PET) imaging) to hippocampus volume (HV) and episodic memory (EM) in three groups: (i) normal controls (NC) from the Berkeley Aging Cohort (BAC NC, n = 20); (ii) normal controls (NC) from the Alzheimer's disease neuroimaging initiative (ADNI NC, n = 17); and (iii) PIB+ mild cognitive impairment subjects from the ADNI (ADNI PIB+ MCI, n = 39). Age, gender and education were controlled for in each statistical model, and HV was adjusted for intracranial volume (aHV). In BAC NC, elevated PIB uptake was significantly associated with smaller aHV (P = 0.0016) and worse EM (P = 0.0086). Within ADNI NC, elevated PIB uptake was significantly associated with smaller aHV (P = 0.047) but not EM (P = 0.60); within ADNI PIB+ MCI, elevated PIB uptake was significantly associated with both smaller aHV (P = 0.00070) and worse EM (P = 0.046). To further understand these relationships, a recursive regression procedure was conducted within all ADNI NC and PIB+ MCI subjects (n = 56) to test the hypothesis that HV mediates the relationship between Aβ and EM. Significant correlations were found between PIB index and EM (P = 0.0044), PIB index and aHV (P < 0.0001), as well as between aHV and EM (P < 0.0001). When both aHV and PIB were included in the same model to predict EM, aHV remained significant (P = 0.0015) whereas PIB index was no longer significantly associated with EM (P = 0.50). These results are consistent with a model in which Aβ deposition, hippocampal atrophy, and EM occur sequentially in elderly subjects, with Aβ deposition as the primary event in this cascade. This pattern suggests that declining EM in older individuals may be caused by Aβ-induced hippocampus atrophy.
Although β-amyloid (Aβ) plaques are a primary diagnostic criterion for Alzheimer's disease, this pathology is commonly observed in the brains of non-demented older individuals. To explore the ...importance of this pathology in the absence of dementia, we compared levels of amyloid deposition (via 'Pittsburgh Compound-B' (PIB) positron emission tomography (PET) imaging) to hippocampus volume (HV) and episodic memory (EM) in three groups: (i) normal controls (NC) from the Berkeley Aging Cohort (BAC NC, n = 20); (ii) normal controls (NC) from the Alzheimer's disease neuroimaging initiative (ADNI NC, n = 17); and (iii) PIB+ mild cognitive impairment subjects from the ADNI (ADNI PIB+ MCI, n = 39). Age, gender and education were controlled for in each statistical model, and HV was adjusted for intracranial volume (aHV). In BAC NC, elevated PIB uptake was significantly associated with smaller aHV (P = 0.0016) and worse EM (P = 0.0086). Within ADNI NC, elevated PIB uptake was significantly associated with smaller aHV (P = 0.047) but not EM (P = 0.60); within ADNI PIB+ MCI, elevated PIB uptake was significantly associated with both smaller aHV (P = 0.00070) and worse EM (P = 0.046). To further understand these relationships, a recursive regression procedure was conducted within all ADNI NC and PIB+ MCI subjects (n = 56) to test the hypothesis that HV mediates the relationship between Aβ and EM. Significant correlations were found between PIB index and EM (P = 0.0044), PIB index and aHV (P < 0.0001), as well as between aHV and EM (P < 0.0001). When both aHV and PIB were included in the same model to predict EM, aHV remained significant (P = 0.0015) whereas PIB index was no longer significantly associated with EM (P = 0.50). These results are consistent with a model in which Aβ deposition, hippocampal atrophy, and EM occur sequentially in elderly subjects, with Aβ deposition as the primary event in this cascade. This pattern suggests that declining EM in older individuals may be caused by Aβ-induced hippocampus atrophy.
Centromeres form the site of chromosome attachment to microtubules during mitosis. Identity of these loci is maintained epigenetically by nucleosomes containing the histone H3 variant CENP-A. ...Propagation of CENP-A chromatin is uncoupled from DNA replication initiating only during mitotic exit. We now demonstrate that inhibition of Cdk1 and Cdk2 activities is sufficient to trigger CENP-A assembly throughout the cell cycle in a manner dependent on the canonical CENP-A assembly machinery. We further show that the key CENP-A assembly factor Mis18BP1HsKNL2 is phosphorylated in a cell cycle-dependent manner that controls its centromere localization during mitotic exit. These results strongly support a model in which the CENP-A assembly machinery is poised for activation throughout the cell cycle but kept in an inactive noncentromeric state by Cdk activity during S, G2, and M phases. Alleviation of this inhibition in G1 phase ensures tight coupling between DNA replication, cell division, and subsequent centromere maturation.
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► CENP-A assembly machinery is present throughout the cell cycle ► Onset of CENP-A assembly in G1 phase is triggered by loss of Cdk1 activity ► Cdk1 and Cdk2 are sufficient to inhibit CENP-A assembly prior to mitosis ► Centromere localization of Mis18BP1 is controlled by phosphorylation
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The formation of two-dimensional electron gases (2DEGs) at complex oxide interfaces is directly influenced by the oxide electronic properties. We investigated how local electron correlations control ...the 2DEG by inserting a single atomic layer of a rare-earth oxide (RO) (R is lanthanum (La), praseodymium (Pr), neodymium (Nd), samarium (Sm), or yttrium (Y) into an epitaxial strontium titanate oxide (SrTiO₃) matrix using pulsed-laser deposition with atomic layer control. We find that structures with La, Pr, and Nd ions result in conducting 2DEGs at the inserted layer, whereas the structures with Sm or Y ions are insulating. Our local spectroscopic and theoretical results indicate that the interfacial conductivity is dependent on electronic correlations that decay spatially into the SrTiO₃ matrix. Such correlation effects can lead to new functionalities in designed heterostructures.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
The North American Nanohertz Observatory for Gravitational Waves (NANOGrav) has observed dozens of millisecond pulsars for over a decade. We have accrued a large collection of dispersion measure (DM) ...measurements sensitive to the total electron content between Earth and the pulsars at each observation. All lines of sight cross through the solar wind (SW), which produces correlated DM fluctuations in all pulsars. We develop and apply techniques for extracting the imprint of the SW from the full collection of DM measurements in the recently released NANOGrav 11 yr data set. We filter out long-timescale DM fluctuations attributable to structure in the interstellar medium and carry out a simultaneous analysis of all pulsars in our sample that can differentiate the correlated signature of the wind from signals unique to individual lines of sight. When treating the SW as spherically symmetric and constant in time, we find the electron number density at 1 au to be 7.9 0.2 cm−3. We find our data to be insensitive to long-term variation in the density of the wind. We argue that our techniques paired with a high-cadence, low-radio-frequency observing campaign of near-ecliptic pulsars would be capable of mapping out large-scale latitudinal structure in the wind.
We report on analysis of englacial radio-frequency (RF) pulser data received over horizontal baselines of 1–5 km, based on broadcasts from two sets of transmitters deployed to depths of up to 1500 ...meters at the South Pole. First, we analyze data collected using two RF bicone transmitters 1400 meters below the ice surface, and frozen into boreholes drilled for the IceCube experiment in 2011. Additionally, in Dec., 2018, a fat-dipole antenna, fed by one of three high-voltage ( (1 kV)), fast ( (1-5 ns risetime)) signal generators was lowered into the 1700-m deep icehole drilled for the South Pole Ice Core Experiment (SPICE), approximately 3 km from the geographic South Pole. Signals from transmitters were recorded on the five englacial multi-receiver ARA stations, with receiver depths between 60–200 m. From analysis of deep transmitter data, we estimate: i) the range of refractive index profiles of Antarctic ice with depth allowed by our measurements, ii) due to birefringence, a time difference between arrival times for vertically polarized vs. horizontally polarized signals (per km) for horizontally propagating signal, and iii) for the first time, the attenuation length for electromagnetic signals in the radio-frequency regime broadcast horizontally (rather than reflected vertically from bedrock). We additionally present data suggesting anomalous ice propagation effects, and contrary to expectations for a transport medium with a smoothly varying refractive index profile. Our results imply negligible uncertainty in overall neutrino detection volume due to refractive index uncertainties. Our birefringence time-difference measurements are fit to the functional form δt(H−V)ns/km=acosθ+b, with H/V the signal arrival times for the horizontally/vertically polarized EM signal components, and θ the opening angle in the horizontal plane between the signal propagation direction and the local ice flow direction, extracting a=8.3±1.3 ns/km, and b=-8.6±0.9 ns/km (errors combined statistical and systematic), allowing a ∼15% range estimate for future measurements of in-ice neutrino interactions. Finally, we find attenuation length values clustering around 1.5 km, with measurements from the bicone transmitters yielding Latten=1.43±0.25±0.37 km. Taken together, these measurements support cold polar ice as a near-optimal platform for ultra-high energy neutrino detectors.
Triply differential (e,2e) studies of phenol da Silva, G B; Neves, R F C; Chiari, L ...
Journal of chemical physics online/The Journal of chemical physics/Journal of chemical physics,
09/2014, Volume:
141, Issue:
12
Journal Article
Peer reviewed
Open access
We have measured (e,2e) triple differential cross sections (TDCS) for the electron-impact ionisation of phenol with coplanar asymmetrical kinematics for an incident electron energy of 250 eV. ...Experimental measurements of the angular distribution of the slow outgoing electrons at 20 eV are obtained when the incident electron scatters through angles of -5°, -10°, and -15°, respectively. The TDCS data are compared with calculations performed within the molecular 3-body distorted wave model. In this case, a mixed level of agreement, that was dependent on the kinematical condition being probed, was observed between the theoretical and experimental results in the binary peak region. The experimental intensity of the recoil features under all kinematical conditions was relatively small, but was still largely underestimated by the theoretical calculations.
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