Regulation of axon repulsion by MAX-1 SUMOylation and AP-3.

During neural development, growing axons express specific surface receptors in response to various environmental guidance cues. These axon guidance receptors are regulated through intracellular trafficking and degradation to enable navigating axons to reach their targets. In Caenorhabditis elegans, the UNC-5 receptor is necessary for dorsal migration of developing motor axons. We previously found that MAX-1 is required for UNC-5-mediated axon repulsion, but its mechanism of action remained unclear. Here, we demonstrate that UNC-5-mediated axon repulsion in C. elegans motor axons requires both max-1 SUMOylation and the AP-3 complex β subunit gene, apb-3 Genetic interaction studies show that max-1 is SUMOylated by gei-17/PIAS1 and acts upstream of apb-3 Biochemical analysis suggests that constitutive interaction of MAX-1 and UNC-5 receptor is weakened by MAX-1 SUMOylation and by the presence of APB-3, a competitive interactor with UNC-5. Overexpression of APB-3 reroutes the trafficking of UNC-5 receptor into the lysosome for protein degradation. In vivo fluorescence recovery after photobleaching experiments shows that MAX-1 SUMOylation and APB-3 are required for proper trafficking of UNC-5 receptor in the axon. Our results demonstrate that SUMOylation of MAX-1 plays an important role in regulating AP-3-mediated trafficking and degradation of UNC-5 receptors during axon guidance

Exploring the Identification of Expertise: An Experiment in a Computer Software Corporation

People recognize and express their expertise in several ways. In one way, workers can build personal profile to list their expertise. They recall their working experience and write some keyword terms in their personal profiles. In the other way, workers can build expertise in extracting from any documents they provided that includes studying documents, working documents or published papers. We want to know how the workers in the computer software corporation recognize and identify their expertise and explore the heuristics in identification of the expertise. We made an experiment comprised the above methods and invited 25 persons in a computer software corporation to participate and explore how they identify their expertise. During the experiment process, we found that (1) for most people, it’s hard to tell what expertise they completely have without any hint; (2) except these two ways, researchers or practitioners must innovate other methods to identify or elicit human’s expertise; (3) expertise in particular domain is rather than single term, but also multiple complex and related term sets; (4) expertise would be different with different audiences

Enhancement of radiosensitivity in human glioblastoma cells by the DNA N-mustard alkylating agent BO-1051 through augmented and sustained DNA damage response

<p>Abstract</p> <p>Background</p> <p>1-{4-[Bis(2-chloroethyl)amino]phenyl}-3-[2-methyl-5-(4-methylacridin-9-ylamino)phenyl]urea (BO-1051) is an N-mustard DNA alkylating agent reported to exhibit antitumor activity. Here we further investigate the effects of this compound on radiation responses of human gliomas, which are notorious for the high resistance to radiotherapy.</p> <p>Methods</p> <p>The clonogenic assay was used to determine the IC₅₀and radiosensitivity of human glioma cell lines (U87MG, U251MG and GBM-3) following BO-1051. DNA histogram and propidium iodide-Annexin V staining were used to determine the cell cycle distribution and the apoptosis, respectively. DNA damage and repair state were determined by γ-H2AX foci, and mitotic catastrophe was measure using nuclear fragmentation. Xenograft tumors were measured with a caliper, and the survival rate was determined using Kaplan-Meier method.</p> <p>Results</p> <p>BO-1051 inhibited growth of human gliomas in a dose- and time-dependent manner. Using the dosage at IC₅₀, BO-1051 significantly enhanced radiosensitivity to different extents [The sensitizer enhancement ratio was between 1.24 and 1.50 at 10% of survival fraction]. The radiosensitive G₂/M population was raised by BO-1051, whereas apoptosis and mitotic catastrophe were not affected. γ-H2AX foci was greatly increased and sustained by combined BO-1051 and γ-rays, suggested that DNA damage or repair capacity was impaired during treatment. <it>In vivo </it>studies further demonstrated that BO-1051 enhanced the radiotherapeutic effects on GBM-3-beared xenograft tumors, by which the sensitizer enhancement ratio was 1.97. The survival rate of treated mice was also increased accordingly.</p> <p>Conclusions</p> <p>These results indicate that BO-1051 can effectively enhance glioma cell radiosensitivity <it>in vitro </it>and <it>in vivo</it>. It suggests that BO-1051 is a potent radiosensitizer for treating human glioma cells.</p

Assessing the Effects of Acupuncture by Comparing Needling the Hegu Acupoint and Needling Nearby Nonacupoints by Spectral Analysis of Microcirculatory Laser Doppler Signals

We aimed to assess the effects of acupuncture by analyzing the frequency content of skin blood-flow signals simultaneously recorded at the Hegu acupoint and two nearby nonacupoints following acupuncture stimulation (AS). Laser Doppler flowmetry (LDF) signals were measured in male healthy volunteers in two groups of experiments: needling the Hegu acupoint (n = 13) and needling a nearby nonacupoint (control experiment; n = 10). Each experiment involved recording a 20 min baseline-data sequence and two sets of effects data recorded 0–20 and 50–70 min after stopping AS. Wavelet transform with Morlet mother wavelet was applied to the measured LDF signals. Needling the Hegu acupoint significantly increased the blood flow, significantly decreased the relative energy contribution at 0.02–0.06 Hz and significantly increased the relative energy contribution at 0.4–1.6 Hz at Hegu, but induced no significant changes at the nonacupoints. Also, needling a nearby nonacupoint had no effect in any band at any site. This is the first time that spectral analysis has been used to investigate the microcirculatory blood-flow responses induced by AS, and has revealed possible differences in sympathetic nerve activities between needling the Hegu acupoint and its nearby nonacupoint. One possible weakness of the present design is that different De-Qi feelings following AS could lead to nonblind experimental setup, which may bias the comparison between needling Hegu and its nearby nonacupoint. Our results suggest that the described noninvasive method can be used to evaluate sympathetic control of peripheral vascular activity, which might be useful for studying the therapeutic effects of AS

Elderly Patients with Laryngeal and Hypopharyngeal Cancer Undergoing Total Pharyngolaryngectomy with a Radial Forearm, Free Flap-reconstructed Phonation Tube

SummaryBackgroundThe radial forearm, free-flap (RFFF)-reconstructed phonation tube was developed for functional restoration of voice after total pharyngolaryngectomy. We aimed to report the efficacy of RFFF phonation tube after pharyngolaryngectomy with radiotherapy (RT) or concurrent chemoradiation therapy (CCRT) with intensity-modulated radiotherapy (IMRT) for elderly.Materials and methodsTen patients with laryngeal and hypopharyngeal cancer underwent total pharyngolaryngectomy and one-stage reconstruction with an RFFF-accompanied phonation tube, followed by RT or CCRT. Voice restoration was achieved with the RFFF-reconstructed phonation tube. Functional outcomes of phonation and speech were evaluated and scored.ResultsPercentages of stage III and stage IV patients among all participants were 10% and 90%, respectively. The median follow-up time was 31 months (range, 4–67 months). Almost 9 out of 10 (90%) patients experienced phonation efficacy greater than 80%. The maximal phonation time per breath was 70% longer than 3 sec. The graded as mild of wet voice was 90%. Percentage of mild decreased loudness was 60% and that of low and high pitch was 80%. Of the 10 patients, 40% could count more than 10 and 70% could pronounce more than 1 to 5 words per breath. After RT or CCRT, of patients had moderately good to excellent speech intelligibility.ConclusionThe RFFF phonation tube that was used after pharyngolaryngectomy with RT or CCRT with IMRT provided acceptable complications and functional restoration of voice for elderly patients

The Design and Implementation of Collaborative Filtering in Data Mining

Data mining is the process of discovering explicit knowledge from large amounts of data stored in database, data warehouse or other repositories. There have been many studies about models of data mining such as association rule, sequential pattern and so on. Collaborative filtering is one of data mining models. In this paper, we propose two approaches to solving the mining process of collaborative filtering. Finally, collaborative filtering mining is applied to Knowledge Management system