Structural and Functional Characterization of Non-Homologous End Joining Factors

DNA double strand breaks represent the most toxic form of DNA damage. In mammals, non-homologous end-joining (NHEJ) is the primary DNA repair pathway for such damage, preventing both carcinogenesis and accelerated aging. Structural understanding of this repair pathway has received considerable attention, but has been significantly limited by the inability to obtain structures of higher order nucleoprotein complexes. A main obstacle in this respect has been difficulty in obtaining highly purified proteins, sufficient for structural determination. Improved protein expression and purification methods developed in this thesis permitted several NHEJ complexes to be selected for structural studies. Among these, Ku70-DNA and Ku70-DNA-PAXX yielded promising preliminary results. In depth optimization for crystal growth was performed and resulted in a full-length PAXX homodimer structure as well as low-resolution diffraction data for a novel Ku70-DNA complex. The PAXX structure confirmed prior suggestions that the C-terminal region of PAXX is highly disordered

Image Super-Resolution Reconstruction Based On L1/2 Sparsity

Based on image sparse representation in the shearlet domain, we proposed a L1/2 sparsity regularized unconvex variation model for image super-resolution. The L1/2 regularizer term constrains the underlying image to have a sparse representation in shearlet domain. The fidelity term restricts the consistency with the measured imaged in terms of the data degradation model. Then, the variable splitting algorithm is used to break down the model into a series of constrained optimization problems which can be solved by alternating direction method of multipliers. Experimental results demonstrate the effectiveness of the proposed method, both in its visual effects and in quantitative terms

Knock Suppression of a Spark-Ignition Aviation Piston Engine Fuelled with Kerosene

Spark-ignition (SI) engine has a high power density, making it suitable for unmanned aerial vehicles. Normally, gasoline fuel with a high octane number (ON) is used for a spark-ignition engine. However, gasoline fuel is easy to be evaporated and has a low flash point which is unsafe for aviation engines. Kerosene with a high flash point is safer than gasoline. In this chapter, the combustion characteristics of kerosene for a spark-ignition aviation piston engine are analyzed. A three-dimensional (3D) model is setup, and the combustion process of the engine fuelled with kerosene is simulated. Later, the knock limit extension by water injection is evaluated experimentally. The results indicate that water injection can suppress the knock of SI engine with kerosene in some extent and the output power can be improved significantly

Conforming an Extracorporeal Lithotripter System for Video Urodynamic Studies

Objectives: This study aimed to evaluate the efficiency using existing fluoroscopic unit and lithotripter table of an extracorporeal lithotripter system for video urodynamic studies (VUDS) to determine anatomical abnormalities in patients with neurogenic lower urinary tract dysfunction (NLUTD). Methods: The extracorporeal lithotripsy system was adapted to obtain optimum fluoroscopic view according to body shape and observed organs of patients. We reviewed the VUDS data of 25 patients with NLUTD. Results: “Christmas tree bladder” (CTB) was found in 5 (20%) patients. Vesicoureteral reflux (VUR) and external detrusor sphincter dyssynergia (DESD) were detected in 3 (12%) and 4 (16%) patients, respectively. Four (16%) patients with normal coordination between detrusor contraction and external sphincter relaxation were proven by VUDS. CTB, VUR, or DESD was not observed in 10 (40%) patients with flaccid bladder. Hematuria, urinary tract infection, or autonomic dysreflexia did not occur in any of the patients. Conclusions: VUDS can discern anatomical abnormalities of the urinary tract, and patients in undeveloped areas of the world who have NLUTD can have easier access to VUDS because of the decreasing capital cost of VUDS

Disrupted functional connectome in antisocial personality disorder

Studies on antisocial personality disorder (ASPD) subjects focus on brain functional alterations in relation to antisocial behaviors. Neuroimaging research has identified a number of focal brain regions with abnormal structures or functions in ASPD. However, little is known about the connections among brain regions in terms of inter-regional whole-brain networks in ASPD patients, as well as possible alterations of brain functional topological organization. In this study, we employ resting-state functional magnetic resonance imaging (R-fMRI) to examine functional connectome of 32 ASPD patients and 35 normal controls by using a variety of network properties, including small-worldness, modularity, and connectivity. The small-world analysis reveals that ASPD patients have increased path length and decreased network efficiency, which implies a reduced ability of global integration of whole-brain functions. Modularity analysis suggests ASPD patients have decreased overall modularity, merged network modules, and reduced intra- and inter-module connectivities related to frontal regions. Also, network-based statistics show that an internal sub-network, composed of 16 nodes and 16 edges, is significantly affected in ASPD patients, where brain regions are mostly located in the fronto-parietal control network. These results suggest that ASPD is associated with both reduced brain integration and segregation in topological organization of functional brain networks, particularly in the fronto-parietal control network. These disruptions may contribute to disturbances in behavior and cognition in patients with ASPD. Our findings may provide insights into a deeper understanding of functional brain networks of ASPD

Image Super-Resolution Reconstruction Based on L1/2 Sparsity

Based on image sparse representation in the shearlet domain, we proposed a L1/2 sparsity regularized unconvex variation model for image super-resolution. The L1/2 regularizer term constrains the underlying image to have a sparse representation in shearlet domain. The fidelity term restricts the consistency with the measured imaged in terms of the data degradation model. Then, the variable splitting algorithm is used to break down the model into a series of constrained optimization problems which can be solved by alternating direction method of multipliers. Experimental results demonstrate the effectiveness of the proposed method, both in its visual effects and in quantitative terms

Reduced cortical thickness and increased surface area in antisocial personality disorder

Antisocial Personality Disorder (ASPD), one of whose characteristics is high impulsivity, is of great interest in the field of brain structure and function. However, little is known about possible impairments in the cortical anatomy in ASPD, in terms of cortical thickness and surface area, as well as their possible relationship with impulsivity. In this neuroimaging study, we first investigated the changes of cortical thickness and surface area in ASPD patients, in comparison to those of healthy controls, and then performed correlation analyses between these measures and the ability of impulse control. We found that ASPD patients showed thinner cortex while larger surface area in several specific brain regions, i.e., bilateral superior frontal gyrus, orbitofrontal and triangularis, insula cortex, precuneus, middle frontal gyrus, middle temporal gyrus, and left bank of superior temporal sulcus. In addition, we also found that the ability of impulse control was positively correlated with cortical thickness in the superior frontal gyrus, middle frontal gyrus, orbitofrontal cortex, pars triangularis, superior temporal gyrus, and insula cortex. To our knowledge, this study is the first to reveal simultaneous changes in cortical thickness and surface area in ASPD, as well as their relationship with impulsivity. These cortical structural changes may introduce uncontrolled and callous behavioral characteristic in ASPD patients, and these potential biomarkers may be very helpful in understanding the pathomechanism of ASPD

Genome-Wide Expression Analysis in Down Syndrome: Insight into Immunodeficiency

Down syndrome (DS) is caused by triplication of Human chromosome 21 (Hsa21) and associated with an array of deleterious phenotypes, including mental retardation, heart defects and immunodeficiency. Genome-wide expression patterns of uncultured peripheral blood cells are useful to understanding of DS-associated immune dysfunction. We used a Human Exon microarray to characterize gene expression in uncultured peripheral blood cells derived from DS individuals and age-matched controls from two age groups: neonate (N) and child (C). A total of 174 transcript clusters (gene-level) with eight located on Hsa21 in N group and 383 transcript clusters including 56 on Hsa21 in C group were significantly dysregulated in DS individuals. Microarray data were validated by quantitative polymerase chain reaction. Functional analysis revealed that the dysregulated genes in DS were significantly enriched in two and six KEGG pathways in N and C group, respectively. These pathways included leukocyte trans-endothelial migration, B cell receptor signaling pathway and primary immunodeficiency, etc., which causally implicated dysfunctional immunity in DS. Our results provided a comprehensive picture of gene expression patterns in DS at the two developmental stages and pointed towards candidate genes and molecular pathways potentially associated with the immune dysfunction in DS