To evaluate the advantages of ultra-high-resolution computed tomography (U-HRCT) scans for the quantitative measurement of emphysematous lesions over conventional HRCT scans.
This study included 32 ...smokers under routine clinical care who underwent chest CT performed by a U-HRCT scanner. Chronic obstructive pulmonary disease (COPD) was diagnosed in 13 of the 32 participants. Scan data were reconstructed by 2 different protocols: i) U-HRCT mode with a 1024×1024 matrix and 0.25-mm slice thickness and ii) conventional HRCT mode with a 512×512 matrix and 0.5-mm slice thickness. On both types of scans, lesions of emphysema were quantitatively assessed as percentage of low attenuation volume (LAV%, <-950 Hounsfield units). LAV% values determined for scan data from the U-HRCT and conventional HRCT modes were compared by the Wilcoxon matched-pairs signed rank test. The association between LAV% and forced expiratory volume in 1 s per forced vital capacity (FEV
/FVC) was assessed by the Spearman rank correlation test.
Mean values for LAV% determined for the U-HRCT and conventional HRCT modes were 8.9 ± 8.8% and 7.3 ± 8.4%, respectively (
<0.0001). The correlation coefficients for LAV% and FEV
/FVC on the U-HRCT and conventional HRCT modes were 0.50 and 0.49, respectively (both
<0.01).
Compared with conventional HRCT scans, U-HRCT scans reveal emphysematous lesions in greater detail, and provide slightly increased correlation with airflow limitation.
This paper proposes a directional design method of 2-D nonseparable linear-phase paraunitary filter banks. The proposed method is based on a lattice structure consisting of the 2-D separable DCT ...block and nonseparable support extension processes. Because of the nonseparability, the bases are allowed to be directional with the critically fixed subsampling, overlapping, orthogonal, symmetric, real-valued, and compact support properties. First, a novel vanishing moment (VM) condition is introduced as a suitable directional constraint, where the moment is referred to as the trend VM. The condition forces wavelet filters, i.e., high-pass and bandpass filters, to annihilate trend-surface components. Second, some theoretical properties of TVMs are discussed for general 2-D paraunitary systems, and then, the properties are applied to the lattice parameters. In order to verify the significance, several design examples are shown, the trend-surface annihilation properties are numerically confirmed, and the denoising capability is evaluated for images through shrinkage. It is shown that our proposed transforms yield perceptually preferable results.
Parkinson's disease (PD), a neurological disease suited to gene therapy, is biochemically characterized by a severe decrease in the dopamine content of the striatum. One current strategy for gene ...therapy of PD involves local production of dopamine in the striatum achieved by inducing the expression of enzymes involved in the biosynthetic pathway for dopamine. We previously showed that the coexpression of tyrosine hydroxylase (TH) and aromatic-L-amino-acid decarboxylase (AADC), using two separate adeno-associated virus (AAV) vectors, resulted in more effective dopamine production and more remarkable behavioral recovery in 6-hydroxydopamine-lesioned parkinsonian rats, compared with the expression of TH alone. Not only levels of TH and AADC but also levels of tetrahydrobiopterin (BH4), a cofactor of TH, and GTP cyclohydrolase I (GCH), a rate-limiting enzymes for BH4 biosynthesis, are reduced in parkinsonian striatum. In the present study, we investigated whether transduction with separate AAV vectors expressing TH, AADC, and GCH was effective for gene therapy of PD. In vitro experiments showed that triple transduction with AAV-TH, AAV-AADC, and AAV-GCH resulted in greater dopamine production than double transduction with AAV-TH and AAV-AADC in 293 cells. Furthermore, triple transduction enhanced BH4 and dopamine production in denervated striatum of parkinsonian rats and improved the rotational behavior of the rats more efficiently than did double transduction. Behavioral recovery persisted for at least 12 months after stereotaxic intrastriatal injection. These results suggest that GCH, in addition to TH and AADC, is important for effective gene therapy of PD.
Human mutations in PQBP1, a molecule involved in transcription and splicing, result in a reduced but architecturally normal brain. Examination of a conditional Pqbp1-knockout (cKO) mouse with ...microcephaly failed to reveal either abnormal centrosomes or mitotic spindles, increased neurogenesis from the neural stem progenitor cell (NSPC) pool or increased cell death in vivo. Instead, we observed an increase in the length of the cell cycle, particularly for the M phase in NSPCs. Corresponding to the developmental expression of Pqbp1, the stem cell pool in vivo was decreased at E10 and remained at a low level during neurogenesis (E15) in Pqbp1-cKO mice. The expression profiles of NSPCs derived from the cKO mouse revealed significant changes in gene groups that control the M phase, including anaphase-promoting complex genes, via aberrant transcription and RNA splicing. Exogenous Apc4, a hub protein in the network of affected genes, recovered the cell cycle, proliferation, and cell phenotypes of NSPCs caused by Pqbp1-cKO. These data reveal a mechanism of brain size control based on the simple reduction of the NSPC pool by cell cycle time elongation. Finally, we demonstrated that in utero gene therapy for Pqbp1-cKO mice by intraperitoneal injection of the PQBP1-AAV vector at E10 successfully rescued microcephaly with preserved cortical structures and improved behavioral abnormalities in Pqbp1-cKO mice, opening a new strategy for treating this intractable developmental disorder.
Transcription factors involved in the specification and differentiation of neurons often continue to be expressed in the adult brain, but remarkably little is known about their late functions. Nurr1, ...one such transcription factor, is essential for early differentiation of midbrain dopamine (mDA) neurons but continues to be expressed into adulthood. In Parkinson's disease, Nurr1 expression is diminished and mutations in the Nurr1 gene have been identified in rare cases of disease; however, the significance of these observations remains unclear. Here, a mouse strain for conditional targeting of the Nurr1 gene was generated, and Nurr1 was ablated either at late stages of mDA neuron development by crossing with mice carrying Cre under control of the dopamine transporter locus or in the adult brain by transduction of adeno-associated virus Cre-encoding vectors. Nurr1 deficiency in maturing mDA neurons resulted in rapid loss of striatal DA, loss of mDA neuron markers, and neuron degeneration. In contrast, a more slowly progressing loss of striatal DA and mDA neuron markers was observed after ablation in the adult brain. As in Parkinson's disease, neurons of the substantia nigra compacta were more vulnerable than cells in the ventral tegmental area when Nurr1 was ablated at late embryogenesis. The results show that developmental pathways play key roles for the maintenance of terminally differentiated neurons and suggest that disrupted function of Nurr1 and other developmental transcription factors may contribute to neurodegenerative disease.
A local increase in amyloid-beta peptide (Abeta) is closely associated with synaptic dysfunction in the brain in Alzheimer's disease. Here, we report on the catabolic mechanism of Abeta at the ...presynaptic sites. Neprilysin, an Abeta-degrading enzyme, expressed by recombinant adeno-associated viral vector-mediated gene transfer, was axonally transported to presynaptic sites through afferent projections of neuronal circuits. This gene transfer abolished the increase in Abeta levels in the hippocampal formations of neprilysin-deficient mice and also reduced the increase in young mutant amyloid precursor protein transgenic mice. In the latter case, Abeta levels in the hippocampal formation contralateral to the vector-injected side were also significantly reduced as a result of transport of neprilysin from the ipsilateral side, and in both sides soluble Abeta was degraded more efficiently than insoluble Abeta. Furthermore, amyloid deposition in aged mutant amyloid precursor protein transgenic mice was remarkably decelerated. Thus, presynaptic neprilysin has been demonstrated to degrade Abeta efficiently and to retard development of amyloid pathology.
This paper proposes a boundary operation technique of 2-D nonseparable linear-phase paraunitary filter banks (NS-LPPUFBs) for size limitation. The proposed technique is based on a lattice structure ...consisting of the 2-D separable block discrete cosine transform and nonseparable support-extension processes. The bases are allowed to be anisotropic with the fixed critically subsampling, overlapping, orthogonal, symmetric, real-valued, and compact-support properties. First, the blockwise implementation is developed so that the basis images can be locally controlled. The local control of basis images is shown to maintain orthogonality. This property leads a basis termination (BT) technique as a boundary operation. The technique overcomes the drawback of NS-LPPUFBs that the popular symmetric extension method is invalid. Through some experimental results of diagonal texture coding, the significance of the BT is verified.
We present the design and fabrication of a 2D monolithic pixelated detector array using metalorganic vapor-phase epitaxy grown thick CdTe epitaxial layers on Si substrates. Each pixel in the array ...consists of a p-CdTe/n-CdTe/n + -Si heterojunction diode structure, and pixels were patterned by cutting deep vertical grooves using a dicing saw. We also developed a low-temperature conductive-epoxy based bonding technique to bond the array to the read out electronic circuit via an interface board. Preliminary evaluation shows that the fabricated array is capable of discriminating energies of the incident radiation and can be applied for the energy discriminating imaging purpose. Moreover, this fabrication technique is useful in developing larger imaging arrays.
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