Cognitive features of familial Alzheimer’s disease

Familial Alzheimer’s disease (FAD) is considered a pathological model for sporadic Alzheimer’s disease (SAD) due to their similarities. The studies described in this thesis aim to address the issue of improving our knowledge of the cognitive features of FAD at early stages of the disease. This is important from the point of view of a better understanding of the pathophysiology of AD and for trial planning. A longitudinal cohort study aimed to provide analysis of the timing and temporal progression of neuropsychological changes in FAD. It found that a paired associative learning task was one of the earliest neuropsychological tests to decline in the asymptomatic phase of the disease. There was evidence of increased year-to-year fluctuations in select neuropsychological tests after the onset of symptoms in some FAD mutation carriers. A prospective study using a novel experimental paradigm for investigating short-term visual memory found that asymptomatic mutation carriers had a specific impairment in object identity and localization binding despite intact memory for object identity and localization per se. The asymptomatic mutation carriers also had normal longterm and short-term memory performance as measured by standard neuropsychological tests. Performance on the binding task showed a significant correlation with total mean hippocampal volume, consistent with the view that the hippocampus is involved in relational binding, regardless of the memory duration. A case study detailing the longitudinal clinical, neuropsychological and structural imaging findings in an individual with a MAPT mutation yielded important insight into the role of the medial temporal lobe (MTL) in memory functions and highlighted the pitfalls in the differential diagnosis of progressive amnestic syndrome. This thesis therefore provides psychological data in the early stages of FAD and offers insights into the role of the MTL in memory functions in AD and related dementia

Numerical investigation of flow unsteadiness and heat transfer on suction surface of rotating airfoils within a gas turbine cascade

The effects of the periodical turbulence and pressure fluctuation on suction surface heat transfer over airfoils of a row of rotor blades with a certain type have been investigated numerically in this paper. The calculation is performed using model with the numerical results of pressure fluctuation and heat transfer performance over 4 sample points being analyzed and compared with existing experimental data. It shows that the static pressure change has significant impact on heat transfer performance of the fore suction surface, especially in the active region of the shock waves formed from the trailing edge of upstream nuzzles. While, for the rear suction surface, the flow turbulence contributes more to the heat transfer change over the surface, due to the reduced pressure oscillation through this region. Phase shifted phenomenon across the surface can be observed for both pressure and heat transfer parameters, which should be a result of turbulence migration and wake passing across the airfoil

High-Resolution Structure of the N-Terminal Endonuclease Domain of the Lassa Virus L Polymerase in Complex with Magnesium Ions

Lassa virus (LASV) causes deadly hemorrhagic fever disease for which there are no vaccines and limited treatments. LASV-encoded L polymerase is required for viral RNA replication and transcription. The functional domains of L–a large protein of 2218 amino acid residues–are largely undefined, except for the centrally located RNA-dependent RNA polymerase (RdRP) motif. Recent structural and functional analyses of the N-terminal region of the L protein from lymphocytic choriomeningitis virus (LCMV), which is in the same Arenaviridae family as LASV, have identified an endonuclease domain that presumably cleaves the cap structures of host mRNAs in order to initiate viral transcription. Here we present a high-resolution crystal structure of the N-terminal 173-aa region of the LASV L protein (LASV L173) in complex with magnesium ions at 1.72 Å. The structure is highly homologous to other known viral endonucleases of arena- (LCMV NL1), orthomyxo- (influenza virus PA), and bunyaviruses (La Crosse virus NL1). Although the catalytic residues (D89, E102 and K122) are highly conserved among the known viral endonucleases, LASV L endonuclease structure shows some notable differences. Our data collected from in vitro endonuclease assays and a reporter-based LASV minigenome transcriptional assay in mammalian cells confirm structural prediction of LASV L173 as an active endonuclease. The high-resolution structure of the LASV L endonuclease domain in complex with magnesium ions should aid the development of antivirals against lethal Lassa hemorrhagic fever

Features Extraction and Reconstruction of Country Risk based on Empirical EMD

AbstractIn the application of the Empirical Mode Decomposition (EMD), reconstruction to the intrinsic mode functions (IMFs) which are obtained by EMD is necessary in order to simplify analysis and make reconstruction results of more economic explanatory power. At present, there are two main reconstruction methods; one is based on the changing of data construction, represented by the fine- to-coarse method, the other one takes the correlation of the IMFs into consideration, for example, calculating the correlation between the marginal spectrums of different IMFs. In order to study the internal unity and differences between the two methods, country risk data of the BRICS countries are selected to make the empirical analysis. The results are as follows. Firstly, it is not reasonable that the residue obtained by the EMD is directly regarded as the trend of the original data. Secondly, by fine-to-coarse, all the IMFs can be reconstructed to three time scales, which are denoted as high-frequency mode, low-frequency mode and trend respectively, but explanation of these scales for the real situation is not satisfactory. At last, trend which is extracted based on the correlation of the IMF marginal spectrums can describe the basic behavior of the original data. Contrasted to fine-to-coarse, the results obtained by the second method are more reasonable

3,3,6,6,9,9-Hexamethyl-2,3,4,5,6,7,8,9-octa­hydro-1H-xanthene-1,8-dione

The title compound, C19H26O3, was synthesized directly from the condensation of 5,5-dimethyl­cyclo­hexane-1,3-dione with malononitrile catalysed by palladium chloride: there are two molecules in the asymmetric unit

Online Metro Origin-Destination Prediction via Heterogeneous Information Aggregation

Metro origin-destination prediction is a crucial yet challenging time-series analysis task in intelligent transportation systems, which aims to accurately forecast two specific types of cross-station ridership, i.e., Origin-Destination (OD) one and Destination-Origin (DO) one. However, complete OD matrices of previous time intervals can not be obtained immediately in online metro systems, and conventional methods only used limited information to forecast the future OD and DO ridership separately. In this work, we proposed a novel neural network module termed Heterogeneous Information Aggregation Machine (HIAM), which fully exploits heterogeneous information of historical data (e.g., incomplete OD matrices, unfinished order vectors, and DO matrices) to jointly learn the evolutionary patterns of OD and DO ridership. Specifically, an OD modeling branch estimates the potential destinations of unfinished orders explicitly to complement the information of incomplete OD matrices, while a DO modeling branch takes DO matrices as input to capture the spatial-temporal distribution of DO ridership. Moreover, a Dual Information Transformer is introduced to propagate the mutual information among OD features and DO features for modeling the OD-DO causality and correlation. Based on the proposed HIAM, we develop a unified Seq2Seq network to forecast the future OD and DO ridership simultaneously. Extensive experiments conducted on two large-scale benchmarks demonstrate the effectiveness of our method for online metro origin-destination prediction

Proteolytic Processing of Rubella Virus Nonstructural Proteins

AbstractThe genomic RNA of rubella virus contains two long open reading frames (ORF), a 5′-proximal ORF that codes for the nonstructural proteins and a 3′-proximal ORF that encodes the structural proteins. The cDNA encoding the nonstructural protein ORF of the wild-type M33 strain of rubella virus has been obtained and sequenced. Comparison between the nonstructural proteins of the M33 and Therien strains of rubella virus revealed a 98% homology in nucleotide sequence and 98.1% in deduced amino acid sequence. To examine the processing of rubella virus nonstructural protein, the complete nonstructural protein ORF was expressed in BHK cells using a pSFV expression vector. Three nonstructural protein products (p200, p150, and p90) with molecular weights of 200, 150, and 90 kDa were identified using antisera raised against synthetic peptides corresponding to regions of the nonstructural proteins. p200 is the polyprotein precursor, while p150 and p90 are the cleavage products. Site-directed mutagenesis of the Cys-1151 residue (one of the catalytic dyad residues of the viral protease) and of the Gly-1300 residue (the viral protease cleavage site) abrogated protease activity and p200 precursor cleavage, respectively. Coexpression of mutant constructs in BHK cells indicated that rubella virus protease can function both in cis and in trans

Glucose-fueled Micromotors with Highly Efficient Visible Light Photocatalytic Propulsion

Synthetic micro/nanomotors fueled by glucose are highly desired for numerous practical applications because of the biocompatibility of their required fuel. However, currently all of the glucose-fueled micro/nanomotors are based on enzyme-catalytic-driven mechanisms, which usually suffer from strict operation conditions and weak propulsion characteristics that greatly limit their applications. Here, we report a highly efficient glucose-fueled cuprous oxide@N-doped carbon nanotube (Cu_2O@N-CNT) micromotor, which can be activated by environment-friendly visible-light photocatalysis. The speeds of such Cu_2O@N-CNT micromotors can reach up to 18.71 μm/s, which is comparable to conventional Pt-based catalytic Janus micromotors usually fueled by toxic H_2O_2 fuel. In addition, the velocities of such motors can be efficiently regulated by multiple approaches, such as adjusting the N-CNT content within the micromotors, glucose concentrations, or light intensities. Furthermore, the Cu_2O@N-CNT micromotors exhibit a highly controllable negative phototaxis behavior (moving away from light sources). Such motors with outstanding propulsion in biological environments and wireless, repeatable, and light-modulated three-dimensional motion control are extremely attractive for future practical applications

Immunogenicity and Protective Efficacy of a Recombinant Pichinde Viral-Vectored Vaccine Expressing Influenza Virus Hemagglutinin Antigen in Pigs

Influenza A virus of swine (IAV-S) is an economically important swine pathogen. The IAV-S hemagglutinin (HA) surface protein is the main target for vaccine development. In this study, we evaluated the feasibility of using the recombinant tri-segmented Pichinde virus (rPICV) as a viral vector to deliver HA antigen to protect pigs against IAV-S challenge. Four groups of weaned pigs (T01–T04) were included in the study. T01 was injected with PBS to serve as a non-vaccinated control. T02 was inoculated with rPICV expressing green fluorescence protein (rPICV-GFP). T03 was vaccinated with rPICV expressing the HA antigen of the IAV-S H3N2 strain (rPICV-H3). T04 was vaccinated with the recombinant HA protein antigen of the same H3N2 strain. Pigs were vaccinated twice at day 0 and day 21 and challenged at day 43 by intra-tracheal inoculation with the homologous H3N2 IAV-S strain. After vaccination, all pigs in T03 and T04 groups were seroconverted and exhibited high titers of plasma neutralizing antibodies. After challenge, high levels of IAV-S RNA were detected in the nasal swabs and bronchioalveolar lavage fluid of pigs in T01 and T02 but not in the T03 and T04 groups. Similarly, lung lesions were observed in T01 and T02, but not in the T03 and T04 groups. No significant difference in terms of protection was observed between the T03 and T04 group. Collectively, our results demonstrate that the rPICV-H3 vectored vaccine elicited protective immunity against IAV-S challenge. This study shows that rPICV is a promising viral vector for the development of vaccines against IAV-S