333 research outputs found

    RORS: Enhanced Rule-based OWL Reasoning on Spark

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    The rule-based OWL reasoning is to compute the deductive closure of an ontology by applying RDF/RDFS and OWL entailment rules. The performance of the rule-based OWL reasoning is often sensitive to the rule execution order. In this paper, we present an approach to enhancing the performance of the rule-based OWL reasoning on Spark based on a locally optimal executable strategy. Firstly, we divide all rules (27 in total) into four main classes, namely, SPO rules (5 rules), type rules (7 rules), sameAs rules (7 rules), and schema rules (8 rules) since, as we investigated, those triples corresponding to the first three classes of rules are overwhelming (e.g., over 99% in the LUBM dataset) in our practical world. Secondly, based on the interdependence among those entailment rules in each class, we pick out an optimal rule executable order of each class and then combine them into a new rule execution order of all rules. Finally, we implement the new rule execution order on Spark in a prototype called RORS. The experimental results show that the running time of RORS is improved by about 30% as compared to Kim & Park's algorithm (2015) using the LUBM200 (27.6 million triples).Comment: 12 page

    A Revisit to the Pretargeting Concept—A Target Conversion

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    Pretargeting is often used as a tumor targeting strategy that provides much higher tumor to non-tumor ratios than direct-targeting using radiolabeled antibody. Due to the multiple injections, pretargeting is investigated less than direct targeting, but the high T/NT ratios have rendered it more useful for therapy. While the progress in using this strategy for tumor therapy has been regularly reviewed in the literature, this review focuses on the nature and quantitative understanding of the pretargeting concept. By doing so, it is the goal of this review to accelerate pretargeting development and translation to the clinic and to prepare the researchers who are not familiar with the pretargeting concept but are interested in applying it. The quantitative understanding is presented in a way understandable to the average researchers in the areas of drug development and clinical translation who have the basic concept of calculus and general chemistry

    Intraperitoneal Injection is Not Always a Suitable Alternative to Intravenous Injection for Radiotherapy

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    Abstract Intraperitoneal (IP) injection is frequently reported to be as effective as intravenous (IV) injection. Because it allows administering a larger volume with more radioactivity, we have investigated this route and the possibility of using it to circumvent the volume constraint we earlier experienced with pretargeting radiotherapy. Using 99mTc as the label, the pharmacokinetics (PK) of the cMORF effector (a DNA analogue) was evaluated after IP or IV injection in normal mice by necropsy and SPECT/CT imaging. In another experiment, nude mice bearing tumors were used and they received MORF-CC49 pretargeting antibody IV 2 days earlier than labeled cMORF IV or IP. Tumor accumulations of cMORF were measured at 6 hours after its injections. The absorbed radiation doses for 188Re or 90Y pretargeting were estimated using the 99mTc data and a self-absorbed model. Although the absorbed radiation doses to other organs were comparable, the dose to intestines after IP injection was 30-fold higher than IV injection due to the slow entry into the circulation. It had reached such a level as high as the dose to the kidneys that cleared the radioactivity and usually were at the highest level. Nevertheless, the slow entry did not reduce the tumor accumulation. In conclusion, using IP in place of IV led to an unacceptably high absorbed radiation dose to the intestines although the tumor accumulation was not compromised. This effect may be applicable to other radiotherapeutic agents as well

    Differentiation between temporary and real non-clearability of biotinylated IgG antibody by avidin in mice

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    Although an increasing number of antibody conjugates are being used in the clinic, there remain many unmet needs in antibody targeting. Normal tissue background is one of the key issues that limits the therapeutic efficacy and the detection sensitivity. Background reduction coupled with dose increase may provide the required target accumulation of the label or toxin at an acceptable normal tissue background. However, the knowledge about the in vivo interaction between antibody and a clearing agent is currently inadequate for designing a rational clearance regimen or system. The current investigation focuses on the clearability of antibody for background reduction, an important topic to antibody targeting in general. The investigation employs pretargeting as a research tool and avidin as a model clearing agent. By comparing the effects of natural clearance at a longer post-injection time and avidin clearance, we demonstrated that avidin clearance is much more effective. By directly attaching avidin to a biotinylated antibody prior to injection, we found that the biotinylated antibody in blood, once bound to the clearing agent, can be removed from the circulation immediately and completely, while the real non-clearable antibody without biotin stays. The study of multiple avidin injections confirmed that the presence of clearable biotinylated antibodies after an avidin injection is due to their temporary inaccessibility and subsequent return from tissue compartments. The collective clearance efficiency of 91% by three avidin injections indicates a continuous IV infusion would be recommended to remove all of the biotinylated IgG molecules. In conclusion, the use of antibody pretargeting as a tool in this study has improved understanding of the incomplete clearance by avidin and can aid in overcoming this obstacle

    Nonlinear dynamics of postural control system under visual-vestibular habituation balance practice: evidence from EEG, EMG and center of pressure signals

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    Human postural control system is inherently complex with nonlinear interaction among multiple subsystems. Accordingly, such postural control system has the flexibility in adaptation to complex environments. Previous studies applied complexity-based methods to analyze center of pressure (COP) to explore nonlinear dynamics of postural sway under changing environments, but direct evidence from central nervous system or muscular system is limited in the existing literature. Therefore, we assessed the fractal dimension of COP, surface electromyographic (sEMG) and electroencephalogram (EEG) signals under visual-vestibular habituation balance practice. We combined a rotating platform and a virtual reality headset to present visual-vestibular congruent or incongruent conditions. We asked participants to undergo repeated exposure to either congruent (n = 14) or incongruent condition (n = 13) five times while maintaining balance. We found repeated practice under both congruent and incongruent conditions increased the complexity of high-frequency (0.5–20 Hz) component of COP data and the complexity of sEMG data from tibialis anterior muscle. In contrast, repeated practice under conflicts decreased the complexity of low-frequency (<0.5 Hz) component of COP data and the complexity of EEG data of parietal and occipital lobes, while repeated practice under congruent environment decreased the complexity of EEG data of parietal and temporal lobes. These results suggested nonlinear dynamics of cortical activity differed after balance practice under congruent and incongruent environments. Also, we found a positive correlation (1) between the complexity of high-frequency component of COP and the complexity of sEMG signals from calf muscles, and (2) between the complexity of low-frequency component of COP and the complexity of EEG signals. These results suggested the low- or high-component of COP might be related to central or muscular adjustment of postural control, respectively

    Rapid evolutionary divergence of Gossypium barbadense and G. hirsutum mitochondrial genomes

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    Background The mitochondrial genome from upland cotton, G. hirsutum, was previously sequenced. To elucidate the evolution of mitochondrial genomic diversity within a single genus, we sequenced the mitochondrial genome from Sea Island cotton (Gossypium barbadense L.). Methods Mitochondrial DNA from week-old etiolated seedlings was extracted from isolated organelles using discontinuous sucrose density gradient method. Mitochondrial genome was sequenced with Solexa using paired-end, 90 bp read. The clean reads were assembled into contigs using ABySS and finished via additional fosmid and BAC sequencing. Finally, the genome was annotated and analyzed using different softwares. Results The G. barbadense (Sea Island cotton) mitochondrial genome was fully sequenced (677,434-bp) and compared to the mitogenome of upland cotton. The G. barbadensemitochondrial DNA contains seven more genes than that of upland cotton, with a total of 40 protein coding genes (excluding possible pseudogenes), 6 rRNA genes, and 29 tRNA genes. Of these 75 genes, atp1, mttB, nad4, nad9, rrn5, rrn18, and trnD(GTC)-cp were each represented by two identical copies. A single 64 kb repeat was largely responsible for the 9 % difference in genome size between the two mtDNAs. Comparison of genome structures between the two mitochondrial genomes revealed 8 rearranged syntenic regions and several large repeats. The largest repeat was missing from the master chromosome in G. hirsutum. Both mitochondrial genomes contain a duplicated copy of rps3 (rps3-2) in conjunction with a duplication of repeated sequences. Phylogenetic and divergence considerations suggest that a 544-bp fragment of rps3 was transferred to the nuclear genome shortly after divergence of the A- and D- genome diploid cottons. Conclusion These results highlight the insights to the evolution of structural variation between Sea Island and upland cotton mitochondrial genomes

    20-Hydroxyecdysone (20E) Primary Response Gene \u3cem\u3eE93\u3c/em\u3e Modulates 20E Signaling to Promote \u3cem\u3eBombyx\u3c/em\u3e Larval-Pupal Metamorphosis

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    As revealed in a previous microarray study to identify genes regulated by 20-hydroxyecdysone (20E) and juvenile hormone (JH) in the silkworm, Bombyx mori, E93 expression in the fat body was markedly low prior to the wandering stage but abundant during larval-pupal metamorphosis. Induced by 20E and suppressed by JH, E93 expression follows this developmental profile in multiple silkworm alleles. The reduction of E93 expression by RNAi disrupted 20E signaling and the 20E-induced autophagy, caspase activity, and cell dissociation in the fat body. Reducing E93 expression also decreased the expression of the 20E-induced pupal-specific cuticle protein genes and prevented growth and differentiation of the wing discs. Importantly, the two HTH domains in E93 are critical for inducing the expression of a subset of 20E response genes, including EcR, USP, E74, Br-C, and Atg1. By contrast, the LLQHLL and PLDLSAK motifs in E93 inhibit its transcriptional activity. E93 binds to the EcR-USP complex via a physical association with USP through its LLQHLL motif; and this association is enhanced by 20E-induced EcR-USP interaction, which attenuates the transcriptional activity of E93. E93 acts through the two HTH domains to bind to GAGA-containing motifs present in the Atg1 promoter region for inducing gene expression. In conclusion, E93 transcriptionally modulates 20E signaling to promote Bombyx larval-pupal metamorphosis
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