Lacunar-canalicular network in femoral cortical bone is reduced in aged women and is predominantly due to a loss of canalicular porosity

The lacunar-canalicular network (LCN) of bone contains osteocytes and their dendritic extensions, which allow for intercellular communication, and are believed to serve as the mechanosensors that coordinate the processes of bone modeling and remodeling. Imbalances in remodeling, for example, are linked to bone disease, including fragility associated with aging. We have reported that there is a reduction in scale for one component of the LCN, osteocyte lacunar volume, across the human lifespan in females. In the present study, we explore the hypothesis that canalicular porosity also declines with age. To visualize the LCN and to determine how its components are altered with aging, we examined samples from young (age: 20-23 y; n = 5) and aged (age: 70-86 y; n = 6) healthy women donors utilizing a fluorescent labelling technique in combination with confocal laser scanning microscopy. A large cross-sectional area of cortical bone spanning the endosteal to periosteal surfaces from the anterior proximal femoral shaft was examined in order to account for potential trans-cortical variation in the LCN. Overall, we found that LCN areal fraction was reduced by 40.6% in the samples from aged women. This reduction was due, in part, to a reduction in lacunar density (21.4% decline in lacunae number per given area of bone), but much more so due to a 44.6% decline in canalicular areal fraction. While the areal fraction of larger vascular canals was higher in endosteal vs. periosteal regions for both age groups, no regional differences were observed in the areal fractions of the LCN and its components for either age group. Our data indicate that the LCN is diminished in aged women, and is largely due to a decline in the canalicular areal fraction, and that, unlike vascular canal porosity, this diminished LCN is uniform across the cortex

SOX2 Co-Occupies Distal Enhancer Elements with Distinct POU Factors in ESCs and NPCs to Specify Cell State

SOX2 is a master regulator of both pluripotent embryonic stem cells (ESCs) and multipotent neural progenitor cells (NPCs); however, we currently lack a detailed understanding of how SOX2 controls these distinct stem cell populations. Here we show by genome-wide analysis that, while SOX2 bound to a distinct set of gene promoters in ESCs and NPCs, the majority of regions coincided with unique distal enhancer elements, important cis-acting regulators of tissue-specific gene expression programs. Notably, SOX2 bound the same consensus DNA motif in both cell types, suggesting that additional factors contribute to target specificity. We found that, similar to its association with OCT4 (Pou5f1) in ESCs, the related POU family member BRN2 (Pou3f2) co-occupied a large set of putative distal enhancers with SOX2 in NPCs. Forced expression of BRN2 in ESCs led to functional recruitment of SOX2 to a subset of NPC-specific targets and to precocious differentiation toward a neural-like state. Further analysis of the bound sequences revealed differences in the distances of SOX and POU peaks in the two cell types and identified motifs for additional transcription factors. Together, these data suggest that SOX2 controls a larger network of genes than previously anticipated through binding of distal enhancers and that transitions in POU partner factors may control tissue-specific transcriptional programs. Our findings have important implications for understanding lineage specification and somatic cell reprogramming, where SOX2, OCT4, and BRN2 have been shown to be key factors

Structural and micro-anatomical changes in vertebrae associated with idiopathic-type spinal curvature in the curveback guppy model

Background: The curveback lineage of guppy is characterized by heritable idiopathic-type spinal curvature thatdevelops during growth. Prior work has revealed several important developmental similarities to the human idiopathicscoliosis (IS) syndrome. In this study we investigate structural and histological aspects of the vertebrae that areassociated with spinal curvature in the curveback guppy and test for sexual dimorphism that might explain a femalebias for severe curve magnitudes in the population.Methods: Vertebrae were studied from whole-mount skeletal specimens of curved and non-curved adult males andfemales. A series of ratios were used to characterize structural aspects of each vertebra. A three-way analysis of variancetested for effects of sex, curvature, vertebral position along the spine, and all 2-way interactions (i.e., sex and curvature,sex and vertebra position, and vertebra position and curvature). Histological analyses were used to characterize microarchitecturalchanges in affected vertebrae and the intervertebral region.Results: In curveback, vertebrae that are associated with curvature demonstrate asymmetric shape distortion,migration of the intervertebral ligament, and vertebral thickening on the concave side of curvature. There is sexualdimorphism among curved individuals such that for several vertebrae, females have more slender vertebrae than domales. Also, in the region of the spine where lordosis typically occurs, curved and non-curved females have a reducedwidth at the middle of their vertebrae, relative to males.Conclusions: Based on similarities to human spinal curvatures and to animals with induced curves, the concaveconvexbiases described in the guppy suggest that there is a mechanical component to curve pathogenesis incurveback. Because idiopathic-type curvature in curveback is primarily a sagittal deformity, it is structurally more similarto Scheuermann kyphosis than IS. Anatomical differences between teleosts and humans make direct biomechanicalcomparisons difficult. However, study of basic biological systems involved in idiopathic-type spinal curvature incurveback may provide insight into the relationship between a predisposing aetiology, growth, and biomechanics.Further work is needed to clarify whether observed sex differences in vertebral characteristics are related to the femalebias for severe curves that is observed in the population

Text mining of mutations and their impact from biomedical literature

Shanker, Vijay K.The increasing amount of research focusing on genetic mutations has triggered a rapid growth in the number of published articles describing mutations and their effect on diseases, drug responses and protein functionalities. With the advent of precision medicine, which aims at identifying targeted therapies that have maximal efficacy for individual patients, there is a pressing need to gather such mutational information from text into public knowledge bases. But manual curation slows down the growth of such databases. We have applied natural language processing (NLP) techniques to locate and extract mutational information from text that will assist curators and researchers. In particular, in this dissertation, we have addressed the following tasks: mutation detection, mutation to disease association, mutation impact on drug responses and impact of mutations on protein-protein interactions from research literature. ☐ We have developed a system, MeX, to detect a wide range of mutation mentions from text. Evaluations on several publicly available corpora exhibit that we have achieved state-of-the-art performance in mutation detection. The mutation detector also applies a novel algorithm to associate mutations with genes. We have developed a system, DiMeX, which finds the association between mutations and diseases from abstracts of published articles. Our system outperformed the current state-of-the-art when evaluated on multiple corpora. We have developed a system, eGARD, to identify the impact of genomic anomalies on drug responses. Evaluations showed high performance measures from eGARD that will significantly reduce manual curation time. Finally, we have developed a text mining system to extract mutation impact on protein-protein interaction. This type of information will provide further insight into how mutations affect protein functions, and thereby play a role in the development and progression of diseases. Our system outperformed the current state-of-the-art approaches for the task. To enable easier access to data and make it available to computational bioinformatics tools, we have applied DiMeX and eGARD on Medline-scale and stored the results in databases.University of Delaware, Department of Computer and Information SciencesPh.D

Comparison of Rectangular and Circular Microstrip Fed Patch Antennas at 5.76 GHz

A Comparative study of rectangular and circular shape microstrip patch antennas at 5.76 GHz band is presented in this paper. Computer Simulation Technology (CST) microwave studio is used as the software environment to design and compare the performance of the antennas. Based on the results and analysis, it is found that rectangular patch antenna shows about 8 dB higher return loss then return loss of circular patch antenna. In addition, rectangular patch antenna has improved gain value of 7.499 dB then that of the circular patch with gain 7.114 dB. The radiation efficiency of both rectangular and circular shaped microstrip fed patch antennas is nearly the same. &nbsp

Integrated photovoltaic-grid dc fast charging system for electric vehicle: A review of the architecture and control

The fast charger for electric vehicle (EV) is a complex system that incorporates numerous interconnected subsystems. The interactions among these subsystems require a holistic understanding of the system architecture, control, power electronics, and their overall interaction with the electrical grid system. This review paper presents important aspects of a PV-grid integrated dc fast charger—with a special focus on the charging system components, architecture, operational modes, and control. These include the interaction between the PV power source, grid electricity, energy storage unit (ESU) and power electronics for the chargers. A considerable amount of discussion is also dedicated to battery management systems (BMS) and their mutual interactions in the control processes. For the power electronics, the paper evaluates soft switching non-isolated dc-to-dc power converter topologies that can be possibly used as future EV chargers. In addition to these, a brief discussion on the impact of the PV-grid charging on the ac grid and distribution system and their remedial measures are presented. Furthermore, the challenges in regard to the vehicle to grid (V2G) concept are also described. It is envisaged that the information provided in this paper would be useful as a one-stop document for engineers, researchers and others who require information related to the dc fast charging of EV that incorporates a renewable energy source

DiMeX: A Text Mining System for Mutation-Disease Association Extraction.

The number of published articles describing associations between mutations and diseases is increasing at a fast pace. There is a pressing need to gather such mutation-disease associations into public knowledge bases, but manual curation slows down the growth of such databases. We have addressed this problem by developing a text-mining system (DiMeX) to extract mutation to disease associations from publication abstracts. DiMeX consists of a series of natural language processing modules that preprocess input text and apply syntactic and semantic patterns to extract mutation-disease associations. DiMeX achieves high precision and recall with F-scores of 0.88, 0.91 and 0.89 when evaluated on three different datasets for mutation-disease associations. DiMeX includes a separate component that extracts mutation mentions in text and associates them with genes. This component has been also evaluated on different datasets and shown to achieve state-of-the-art performance. The results indicate that our system outperforms the existing mutation-disease association tools, addressing the low precision problems suffered by most approaches. DiMeX was applied on a large set of abstracts from Medline to extract mutation-disease associations, as well as other relevant information including patient/cohort size and population data. The results are stored in a database that can be queried and downloaded at http://biotm.cis.udel.edu/dimex/. We conclude that this high-throughput text-mining approach has the potential to significantly assist researchers and curators to enrich mutation databases

An improved asymmetrical multi-level inverter topology with boosted output voltage and reduced components count

This paper presents an improved Multi-level Inverter topology utilizing the concept of boosting-capacitor and two DC sources with reduced switches count for generating 17-level output. The topology employs 10 unidirectional switches including one bidirectional switch. Comparison with other recent topologies shows that the proposed topology employs a reduced number of devices and better performance. The topology combines the modularity of H-Bridge with the boosting capacity of the switched capacitor topology. Special care is taken while designing the switching strategy for voltage balancing of the capacitors. The authors also have generalized the topology to produce ‘n’ level output. Relevant expressions are also formed and reported. Experimental validation, as well as simulation, is performed, and results are verified. Nearest level control is used as the modulation technique

Schematic diagram of DiMeX.

<p>Schematic diagram of DiMeX.</p