A Subband-Specific Deconvolution Model for MTF Improvement in CT.

The purpose of this research is to achieve uniform spatial resolution in CT (computed tomography) images without hardware modification. The main idea of this study is to consider geometry optics model, which can provide the approximate blurring PSF (point spread function) kernel, which varies according to the distance from X-ray tube to each pixel. The FOV (field of view) was divided into several band regions based on the distance from X-ray source, and each region was deconvolved with different deconvolution kernels. Though more precise calculation for the PSF for deconvolution is possible as the number of subbands increases, we set the number of subbands to 11. 11 subband settings seem to be a balancing point to reduce noise boost, while MTF (modulation transfer function) increase still remains. As the results show, subband-wise deconvolution makes image resolution (in terms of MTF) relatively uniform across the FOV. The results show that spatial resolution in CT images can be uniform across the FOV without using additional equipment. The beauty of this method is that it can be applied to any CT system as long as we know the specific system parameters and determine the appropriate PSF for deconvolution maps of the system. The proposed algorithm shows promising result in improving spatial resolution uniformity while avoiding the excessive noise boost.

Tract-Specific Correlates of Neuropsychological Deficits in Patients with Subcortical Vascular Cognitive Impairment.

The white matter tract-specific correlates of neuropsychological deficits are not fully established in patients with subcortical vascular cognitive impairment (SVCI), where white matter tract damage may be a critical factor in cognitive impairment. The purpose of this study is to investigate the tract-specific correlates of neuropsychological deficits in SVCI patients using tract-specific statistical analysis (TSSA). We prospectively recruited 114 SVCI patients, and 55 age-, gender-, and education-matched individuals with normal cognition (NC). All participants underwent diffusion weighted imaging and neuropsychological testing. We classified tractography results into fourteen major fiber tracts and analyzed group comparison and correlation with cognitive impairments. Relative to NC subjects, SVCI patients showed decreased fractional anisotropy values in bilateral anterior-thalamic radiation, cingulum, superior-longitudinal fasciculus, uncinate fasciculus, corticospinal tract, and left inferior-longitudinal fasciculus. Focal disruptions in specific tracts were associated with specific cognitive impairments. Our findings suggest that disconnection of specific white matter tracts, especially those neighboring and providing connections between gray matter regions important to certain cognitive functions, may contribute to specific cognitive impairments in SVCI.

An Example-Based Multi-Atlas Approach to Automatic Labeling of White Matter Tracts.

We present an example-based multi-atlas approach for classifying white matter (WM) tracts into anatomic bundles. Our approach exploits expert-provided example data to automatically classify the WM tracts of a subject. Multiple atlases are constructed to model the example data from multiple subjects in order to reflect the individual variability of bundle shapes and trajectories over subjects. For each example subject, an atlas is maintained to allow the example data of a subject to be added or deleted flexibly. A voting scheme is proposed to facilitate the multi-atlas exploitation of example data. For conceptual simplicity, we adopt the same metrics in both example data construction and WM tract labeling. Due to the huge number of WM tracts in a subject, it is time-consuming to label each WM tract individually. Thus, the WM tracts are grouped according to their shape similarity, and WM tracts within each group are labeled simultaneously. To further enhance the computational efficiency, we implemented our approach on the graphics processing unit (GPU). Through nested cross-validation we demonstrated that our approach yielded high classification performance. The average sensitivities for bundles in the left and right hemispheres were 89.5% and 91.0%, respectively, and their average false discovery rates were 14.9% and 14.2%, respectively.

A new paradigm for transcription factor TFIIB functionality.

Experimental and bioinformatic studies of transcription initiation by RNA polymerase II (RNAP2) have revealed a mechanism of RNAP2 transcription initiation less uniform across gene promoters than initially thought. However, the general transcription factor TFIIB is presumed to be universally required for RNAP2 transcription initiation. Based on bioinformatic analysis of data and effects of TFIIB knockdown in primary and transformed cell lines on cellular functionality and global gene expression, we report that TFIIB is dispensable for transcription of many human promoters, but is essential for herpes simplex virus-1 (HSV-1) gene transcription and replication. We report a novel cell cycle TFIIB regulation and localization of the acetylated TFIIB variant on the transcriptionally silent mitotic chromatids. Taken together, these results establish a new paradigm for TFIIB functionality in human gene expression, which when downregulated has potent anti-viral effects.

Cortical Correspondence via Sulcal Curve-Constrained Spherical Registration with Application to Macaque Studies.

In this work, we present a novel cortical correspondence method with application to the macaque brain. The correspondence method is based on sulcal curve constraints on a spherical deformable registration using spherical harmonics to parameterize the spherical deformation. Starting from structural MR images, we first apply existing preprocessing steps: brain tissue segmentation using the Automatic Brain Classification tool (ABC), as well as cortical surface reconstruction and spherical parametrization of the cortical surface via Constrained Laplacian-based Automated Segmentation with Proximities (CLASP). Then, initial correspondence between two cortical surfaces is automatically determined by a curve labeling method using sulcal landmarks extracted along sulcal fundic regions. Since the initial correspondence is limited to sulcal regions, we use spherical harmonics to extrapolate and regularize this correspondence to the entire cortical surface. To further improve the correspondence, we compute a spherical registration that optimizes the spherical harmonic parameterized deformation using a metric that incorporates the error over the sulcal landmarks as well as the normalized cross correlation of sulcal depth maps over the whole cortical surface. For evaluation, a normal 18-months-old macaque brain (for both left and right hemispheres) was matched to a prior macaque brain template with 9 manually labeled, major sulcal curves. The results show successful registration using the proposed registration approach. Evaluation results for optimal parameter settings are presented as well.

Cluster-based statistics for brain connectivity in correlation with behavioral measures.

Graph theoretical approaches have successfully revealed abnormality in brain connectivity, in particular, for contrasting patients from healthy controls. Besides the group comparison analysis, a correlational study is also challenging. In studies with patients, for example, finding brain connections that indeed deepen specific symptoms is interesting. The correlational study is also beneficial since it does not require controls, which are often difficult to find, especially for old-age patients with cognitive impairment where controls could also have cognitive deficits due to normal ageing. However, one of the major difficulties in such correlational studies is too conservative multiple comparison correction. In this paper, we propose a novel method for identifying brain connections that are correlated with a specific cognitive behavior by employing cluster-based statistics, which is less conservative than other methods, such as Bonferroni correction, false discovery rate procedure, and extreme statistics. Our method is based on the insight that multiple brain connections, rather than a single connection, are responsible for abnormal behaviors. Given brain connectivity data, we first compute a partial correlation coefficient between every edge and the behavioral measure. Then we group together neighboring connections with strong correlation into clusters and calculate their maximum sizes. This procedure is repeated for randomly permuted assignments of behavioral measures. Significance levels of the identified sub-networks are estimated from the null distribution of the cluster sizes. This method is independent of network construction methods: either structural or functional network can be used in association with any behavioral measures. We further demonstrated the efficacy of our method using patients with subcortical vascular cognitive impairment. We identified sub-networks that are correlated with the disease severity by exploiting diffusion tensor imaging techniques. The identified sub-networks were consistent with the previous clinical findings having valid significance level, while other methods did not assert any significant findings.

Complement factors are secreted in human follicular fluid by granulosa cells and are possible oocyte maturation factors.

AIMS: In this study, we identify components of the complement system present in human follicular fluid that affect oocyte development and maturation. MATERIAL AND METHODS: Using bottom-up liquid chromatography/mass spectrometry/mass spectrometry, we identified complement factors as consistently present in human follicular fluid from 15 different subjects. RESULTS: According to our gene-chip data, these complement factors are actively produced by granulosa cells. CONCLUSIONS: By applying the computational Ingenuity Pathway Analysis software and database we have identified complement pathways that play a role in oocyte maturation and follicular development.

Group-wise cortical correspondence via sulcal curve-constrained entropy minimization.

We present a novel cortical correspondence method employing group-wise registration in a spherical parametrization space for the use in local cortical thickness analysis in human and non-human primate neuroimaging studies. The proposed method is unbiased registration that estimates a continuous smooth deformation field into an unbiased average space via sulcal curve-constrained entropy minimization using spherical harmonic decomposition of the spherical deformation field. We initialize a correspondence by our pair-wise method that establishes a surface correspondence with a prior template. Since this pair-wise correspondence is biased to the choice of a template, we further improve the correspondence by employing unbiased ensemble entropy minimization across all surfaces, which yields a deformation field onto the iteratively updated unbiased average. The specific entropy metric incorporates two terms: the first focused on optimizing the correspondence of automatically extracted sulcal landmarks and the second on that of sulcal depth maps. We also propose an encoding scheme for spherical deformation via spherical harmonics as well as a novel method to choose an optimal spherical polar coordinate system for the most efficient deformation field estimation. The experimental results show evidence that the proposed method improves the correspondence quality in non-human primate and human subjects as compared to the pair-wise method.

A triangulation-invariant method for anisotropic geodesic map computation on surface meshes.

This paper addresses the problem of computing the geodesic distance map from a given set of source vertices to all other vertices on a surface mesh using an anisotropic distance metric. Formulating this problem as an equivalent control theoretic problem with Hamilton-Jacobi-Bellman partial differential equations, we present a framework for computing an anisotropic geodesic map using a curvature-based speed function. An ordered upwind method (OUM)-based solver for these equations is available for unstructured planar meshes. We adopt this OUM-based solver for surface meshes and present a triangulation-invariant method for the solver. Our basic idea is to explore proximity among the vertices on a surface while locally following the characteristic direction at each vertex. We also propose two speed functions based on classical curvature tensors and show that the resulting anisotropic geodesic maps reflect surface geometry well through several experiments, including isocontour generation, offset curve computation, medial axis extraction, and ridge/valley curve extraction. Our approach facilitates surface analysis and processing by defining speed functions in an application-dependent manner.

A large network of interconnected signaling pathways in human ovarian follicles is supported by the gene expression activity of the granulosa cells.

Human follicular fluid (hFF), as an extra oocyte microenvironment, is essential to the biological processes of oocyte development. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we identified 426 proteins as consistently present in hFF from different participants. According to our gene chip data, the granulosa cells in the follicle locally produce 235 of these proteins. These data suggest that the granulosa cells actively participate in the follicular development by synthesizing important molecules to support the activity of pathways that are essential to oocyte development and genomic preservation. The computational Ingenuity Pathway Analysis (IPA) suggests that the identified proteins have well-established functions in the pathways of steroidogenesis, cell-to-cell signaling and interaction, molecular transport, the antioxidative system, interleukin 1 (IL-1) and IL-6 signaling, liver X receptor/retinoid X receptor (LXR/RXR) activation, and the interconnective insulin-like growth factor and lipid metabolism networks. The hFF peptide composition is likely to serve not only the inflammatory follicular state as has been previously suggested; rather, it is a highly diverse and multifunctional environment with several interconnected pathways. These results provide us with important knowledge related to the environment in which the oocyte develops as well as the molecular basis for controlling the process independently of blood supply.

DNA dynamics play a role as a basal transcription factor in the positioning and regulation of gene transcription initiation.

We assess the role of DNA breathing dynamics as a determinant of promoter strength and transcription start site (TSS) location. We compare DNA Langevin dynamic profiles of representative gene promoters, calculated with the extended non-linear PBD model of DNA with experimental data on transcription factor binding and transcriptional activity. Our results demonstrate that DNA dynamic activity at the TSS can be suppressed by mutations that do not affect basal transcription factor binding-DNA contacts. We use this effect to establish the separate contributions of transcription factor binding and DNA dynamics to transcriptional activity. Our results argue against a purely 'transcription factor-centric' view of transcription initiation, suggesting that both DNA dynamics and transcription factor binding are necessary conditions for transcription initiation.

Age-related variations in follicular apolipoproteins may influence human oocyte maturation and fertility potential.

OBJECTIVE: To investigate involvement of specific apolipoproteins in the process of human oocyte maturation and age-related infertility as molecular constituents of follicular fluid. DESIGN: Laboratory-based observational study. SETTING: Basic science laboratory at a large academic institution. PATIENT(S): Follicular fluid obtained from healthy women aged 18 to 45 years undergoing in vitro fertilization for unexplained infertility, ovulatory dysfunction, tubal disease, male factor infertility, or oocyte donation. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Specific concentration of apolipoproteins and content of lipoprotein particles in follicular fluid and blood plasma as related to reproductive aging. RESULT(S): We registered a decline of follicular apolipoprotein A1 (Apo A1) and apolipoprotein CII (Apo CII) and an increase of the apolipoprotein E (Apo E) with age, which parallels a lower number of retrieved mature oocytes in older women. Follicular apolipoprotein A1, apolipoprotein B (Apo B), apolipoprotein E, and apolipoprotein C II are present in diverse heterogeneous complexes including very-low-density lipoproteins (VLDL), intermediate-low-density lipoproteins (IDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL) that vary with patient age and differ from the blood plasma lipoprotein complexes. CONCLUSION(S): Age-related variation in follicular apolipoprotein content and distribution in the cholesterol particles may be associated with the decrease in production of mature oocytes and the age-related decline in fertility potential.

Automatic extraction of sulcal lines on cortical surfaces based on anisotropic geodesic distance.

Analyzing cortical sulci is important for studying cortical morphology and brain functions. Although sulcal lines on cortical surfaces can be defined in various ways, it is critical in a neuroimaging study to define a sulcal line along the valley of a cortical surface with a high curvature within a sulcus. To extract the sulcal lines automatically, we present a new geometric algorithm based on the computation of anisotropic skeletons of sulcal regions. Because anisotropic skeletons are highly adaptive to the anisotropic nature of the surface shape, the resulting sulcal lines lie accurately on the valleys of the sulcal areas. Our sulcal lines remain unchanged under local shape variabilities in different human brains. Through experiments, we show that the errors of the sulcal lines for both synthetic data and real cortical surfaces were nearly as constant as the function of random noise. By measuring the changes in sulcal shape in Alzheimer's disease (AD) patients, we further investigated the effectiveness of the accuracy of our sulcal lines using a large sample of MRI data. This study involved 70 normal controls (n [men/women]: 29/41, age [mean+/-SD]: 71.7+/-4.9 years), and 100 AD subjects (37/63, 72.3+/-5.5). We observe significantly lower absolute average mean curvature and shallower sulcal depth in AD subjects, where the group difference becomes more significant if we measure the quantities along the sulcal lines rather than over the entire sulcal area. The most remarkable difference in the AD patients was the average sulcal depth (control: 11.70 and AD: 11.34).

The bile acid synthesis pathway is present and functional in the human ovary.

BACKGROUND: Bile acids, end products of the pathway for cholesterol elimination, are required for dietary lipid and fat-soluble vitamin absorption and maintain the balance between cholesterol synthesis in the liver and cholesterol excretion. They are composed of a steroid structure and are primarily made in the liver by the oxidation of cholesterol. Cholesterol is also highly abundant in the human ovarian follicle, where it is used in the formation of the sex steroids. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe for the first time evidence that all aspects of the bile acid synthesis pathway are present in the human ovarian follicle, including the enzymes in both the classical and alternative pathways, the nuclear receptors known to regulate the pathway, and the end product bile acids. Furthermore, we provide functional evidence that bile acids are produced by the human follicular granulosa cells in response to cholesterol presence in the culture media. CONCLUSIONS/SIGNIFICANCE: These findings establish a novel pathway present in the human ovarian follicle that has the capacity to compete directly with sex steroid synthesis.

Toward a detailed description of the thermally induced dynamics of the core promoter.

Establishing the general and promoter-specific mechanistic features of gene transcription initiation requires improved understanding of the sequence-dependent structural/dynamic features of promoter DNA. Experimental data suggest that a spontaneous dsDNA strand separation at the transcriptional start site is likely to be a requirement for transcription initiation in several promoters. Here, we use Langevin molecular dynamic simulations based on the Peyrard-Bishop-Dauxois nonlinear model of DNA (PBD LMD) to analyze the strand separation (bubble) dynamics of 80-bp-long promoter DNA sequences. We derive three dynamic criteria, bubble probability, bubble lifetime, and average strand separation, to characterize bubble formation at the transcriptional start sites of eight mammalian gene promoters. We observe that the most stable dsDNA openings do not necessarily coincide with the most probable openings and the highest average strand displacement, underscoring the advantages of proper molecular dynamic simulations. The dynamic profiles of the tested mammalian promoters differ significantly in overall profile and bubble probability, but the transcriptional start site is often distinguished by large (longer than 10 bp) and long-lived transient openings in the double helix. In support of these results are our experimental transcription data demonstrating that an artificial bubble-containing DNA template is transcribed bidirectionally by human RNA polymerase alone in the absence of any other transcription factors.

Correlation between estrogens and serum adipocytokines in premenopausal and postmenopausal women.

OBJECTIVE: The purpose of this study was to investigate the association between serum adipocytokines (adiponectin, resistin, leptin, and tumor necrosis factor alpha [TNF-alpha]) and endogenous estrogen (estrone and estradiol) levels in healthy premenopausal and postmenopausal women. DESIGN: This study included 53 healthy premenopausal women, 45 healthy postmenopausal women, and 10 postmenopausal women with the metabolic syndrome who were participating in general health examinations. A secondary analysis was performed on levels of adiponectin, resistin, leptin, TNF-alpha, estrone (E1), and estradiol (E2). RESULTS: After accounting for body mass index, TNF-alpha was significantly increased (1.5+/-0.1 vs 2.0+/-0.1 pg/mL, P<0.05) in healthy postmenopausal women as compared with healthy premenopausal women, whereas leptin was decreased (5.6+/-1.1 vs 4.0+/-1.1 ng/mL). Estrogen (E1 and E2) was positively correlated with leptin in only healthy premenopausal women, whereas estrogen did not correlate with any adipocytokine in healthy postmenopausal women. In the multiple regression analysis, only leptin significantly contributed to insulin resistance. Combining healthy premenopausal and postmenopausal women, E1 correlated negatively with TNF-alpha (r=-0.23, P<0.05) and positively with leptin (r=0.35, P<0.01) and did not correlate with resistin. E2 correlated negatively with TNF-alpha (r=-0.24, P<0.05) and positively with leptin (r=0.34, P<0.01); it did not correlate with adiponectin or resistin. Leptin might stimulate the increase of plasma gonadotropin-releasing hormone levels, which could result in a positive correlation with estrogen in premenopausal women but not in postmenopausal women. CONCLUSIONS: Estrogen deficiency resulted in increased TNF-alpha levels. Serum leptin levels correlated positively with estrogen levels in premenopausal women. However, the increase in obesity in postmenopausal women increased leptin, which increases insulin resistance.

Prenatal diagnosis of a large subchorionic placental cyst with intracystic hematomas. A case report.

A large intrauterine cyst containing a heterogenous mass was found by ultrasound in the placenta of a 35-year-old gravida 2 para 1 woman. The cyst, measuring 10.9 x 10.1 cm with a heterogenous mass shadow, was attached near the placental cord insertion site. The woman delivered a healthy female baby weighing 3,330 g by cesarean section without complication. A histopathological examination revealed that the lesion was a subchorionic cyst and contained an internal hematoma. Large subchorionic cysts are extremely rare, and secondary hemorrhage within the cyst has not been reported. In this article, we report the case of a woman with a large subchorionic cyst complicated by an intracystic hematoma and review its clinical significance.

Correlations between umbilical and maternal serum resistin levels and neonatal birth weight.

OBJECTIVE: Resistin is a novel hormone secreted by human adipocytes and mononuclear cells. It is expressed in the human placenta, and has been postulated to play a role in the regulation of energy metabolism during pregnancy. However, correlations between umbilical and maternal serum resistin levels and neonatal birth weight remain poorly understood. The purpose of the study was to clarify the correlation between umbilical cord and maternal serum resistin levels and neonatal birth weight. MATERIALS AND METHODS: This study included 37 healthy mothers, neonates. Resistin levels were determined by ELISA, and compared for correlation between umbilical cord and maternal serum resistin levels and neonatal birth weight. RESULTS: The ranges of resistin levels for umbilical and maternal sera were 10.61-40.81 and 1.14-25.54 ng/ml, respectively. Mean umbilical serum resistin level (21.34+/-1.07 ng/ml) was significantly higher than maternal serum resistin level (10.13+/-1.12) (p<0.001). Umbilical serum resistin levels were positively correlated with maternal serum resistin levels (r=0.607, p<0.001) and negatively with neonatal birth weight (r= - 0.345, p=0.037). No significant differences in resistin levels were discovered between the female and male neonates. In addition, there were no correlation between the umbilical resistin levels and maternal body mass indices, umbilical leptin levels, or insulin levels. CONCLUSIONS: It is suggested that resistin not only affects energy homeostasis by existing in high levels in the fetus, but may play an important role in controlling body weight through effective regulation of adipogenesis by negative feedback.