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As the clinical failure of glioblastoma treatment is attributed by multiple components, including myelin-associated infiltration, assessment of the molecular mechanisms underlying such process and identification of the infiltrating cells have been the primary objectives in glioblastoma research. Here, we adopted radiogenomic analysis to screen for functionally relevant genes that orchestrate the process of glioma cell infiltration through myelin and promote glioblastoma aggressiveness. The receptor of the Nogo ligand (NgR1) was selected as the top candidate through Differentially Expressed Genes (DEG) and Gene Ontology (GO) enrichment analysis. Gain and loss of function studies on NgR1 elucidated its underlying molecular importance in suppressing myelin-associated infiltration in vitro and in vivo. The migratory ability of glioblastoma cells on myelin is reversibly modulated by NgR1 during differentiation and dedifferentiation process through deubiquitinating activity of USP1, which inhibits the degradation of ID1 to downregulate NgR1 expression. Furthermore, pimozide, a well-known antipsychotic drug, upregulates NgR1 by post-translational targeting of USP1, which sensitizes glioma stem cells to myelin inhibition and suppresses myelin-associated infiltration in vivo. In primary human glioblastoma, downregulation of NgR1 expression is associated with highly infiltrative characteristics and poor survival. Together, our findings reveal that loss of NgR1 drives myelin-associated infiltration of glioblastoma and suggest that novel therapeutic strategies aimed at reactivating expression of NgR1 will improve the clinical outcome of glioblastoma patients.

Gait, the style of human walking, has been studied as a behavioral characteristic of an individual. Several studies have utilized gait to identify individuals with the aid of machine learning and computer vision techniques. However, there is a lack of studies on the nature of gait, such as the identification power or the uniqueness. This study aims to quantify the uniqueness of gait in a cohort. Three-dimensional full-body joint kinematics were obtained during normal walking trials from 488 subjects using a motion capture system. The joint angles of the gait cycle were converted into gait vectors. Four gait vectors were obtained from each subject, and all the gait vectors were pooled together. Two gait vectors were randomly selected from the pool and tested if they could be accurately classified if they were from the same person or not. The gait from the cohort was classified with an accuracy of 99.71% using the support vector machine with a radial basis function kernel as a classifier. Gait of a person is as unique as his/her facial motion and finger impedance, but not as unique as fingerprints.

Social Network Service (SNS) is a popular and powerful Web service to connect and/or find friends, and the tendency of a user's interest often affects his/her friends who have similar interests. We can 'Collective Intelligence and Social Big Data' through the SNS. If we can track users' preferences in certain boundaries in terms of Web searching, we can we can improve search efficiency and reliability in view of users. In this paper, we analyze correlation - between Social Relation Value and Search Pattern of web users to improve search efficiency and. Social Relation Value indicates degree of relation on latent characteristic among web users who exist in Social Networks. We calculate Social Relation Value in granting association between 'M' topics and 'L' Attributes that are applicable to 'N' Factors(Similarity, Adjacency, Etc.). And then, we analyze the Correlation - between Social Relation Value and Search Pattern by comparing the search result of each web users correspond to input 'Query' based on Social Relation Value calculated according to topics. Consequently, we find that Search Pattern is similar to that of web users who have high Social Relation Value. Namely, web users who have similar characteristic and interact with each other with activity in (Online) Social Networks have high Correlation. Thus, we are able to improve search efficiency and reliability when the correlation is applied to search.

A 16.8 Gbps/channel single-ended transceiver for SiP-based DRAM interface on silicon carrier channel is proposed in this paper. A transmitter, receiver, and channel are all included in a single package as SiP. A current mode 4:1 MUX with 1-tap feed-forward equalizer (FFE) is used as a serializer, and this 4:1 MUX uses 25% duty clock to prevent short circuit current when consecutive 2-phase clocks overlap. Additionally, an open drain output driver with asynchronous type 1-tap FFE is used in the transmitter. Because of its small physical size, a common mode variation of Si-carrier channel from process variation is more serious than that of conventional PCB. This common mode variation degrades bit error rates (BER) at single-ended signaling. To obtain effective single-ended signaling on Si-carrier channel, a source follower-based continuous time linear equalizers and self- ${\rm V}_{\rm REF}$ generator with training algorithm on the receiver are proposed. An implemented Si-carrier channel uses meshed layer as a reference to reduce insertion loss. A BER less than 1e-12 is achieved in 65 nm CMOS and the power efficiency of the transceiver is 5.9 pJ/bit with 120 $\Omega$ terminations at each transceiver side.

Upregulation of microRNA-21 (miR-21) is known to be strongly associated with the proliferation, invasion, and radio-resistance of glioma cells. However, the regulatory mechanism that governs the biogenesis of miR-21 in glioma is still unclear. Here, we demonstrate that the DEAD-box RNA helicase, DDX23, promotes miR-21 biogenesis at the post-transcriptional level. The expression of DDX23 was enhanced in glioma tissues compared to normal brain, and expression level of DDX23 was highly associated with poor survival of glioma patients. Specific knockdown of DDX23 expression suppressed glioma cell proliferation and invasion in vitro and in vivo, which is similar to the function of miR-21. We found that DDX23 increased the level of miR-21 by promoting primary-to-precursor processing of miR-21 through an interaction with the Drosha microprocessor. Mutagenesis experiments critically demonstrated that the helicase activity of DDX23 was essential for the processing (cropping) of miR-21, and we further found that ivermectin, a RNA helicase inhibitor, decreased miR-21 levels by potentially inhibiting DDX23 activity and blocked invasion and cell proliferation. Moreover, treatment of ivermectin decreased glioma growth in mouse xenografts. Taken together, these results suggest that DDX23 plays an essential role in glioma progression, and might thus be a potential novel target for the therapeutic treatment of glioma.

Background Botulinum toxin (BoNT) is widely used to treat masseter muscle hypertrophy. Changes in the muscle thickness have been found in many studies, but there has been no report on changes in the thickness from the skin surface to the masseter muscle. Objectives We aimed to use ultrasonography to measure not only changes in the muscle thickness but also changes in subcutaneous thickness. Methods This study enrolled 20 volunteer patients: 10 were assigned to an experimental group (injected with each side 25 U of botulinum toxin into both masseter muscles) and 10 to a control group (injected with normal saline). The thicknesses were measured before the injection and at 4, 8, and 12 weeks after the injection both at rest and during maximum muscle contraction. Results The subcutaneous thickness did not differ significantly over time either at rest (P = 0.063) or during maximal contraction (P = 0.392), or between the experimental and control groups at rest (P = 0.392) or during maximum contraction (P = 0.259). The muscle thickness in the experimental group differed significantly over time. Conclusions Botulinum toxin injection only changes the muscle thickness and does not affect the subcutaneous thickness from the skin surface to the masseter muscle.

Glioma stemness has been recognized as the most important reason for glioma relapse and drug resistance. Differentiation of glioma stem cells (GSCs) has been implicated as a novel approach to target recurrent glioma. However, the detailed molecular mechanism involved in the differentiation of GSCs has not yet been elucidated. This study identified CPEB1 as the key modulator that induces the differentiation of GSCs at the post-transcriptional level. Gain and loss of function experiments showed that CPEB1 expression reduced sphere formation ability and the expression of stemness markers such as Nestin and Notch. To elucidate the detailed molecular mechanism underlying the action of CPEB1, we investigated the interacting ribonome of the CPEB1 complex using a Ribonomics approach. CPEB1 specifically suppressed the translation of HES1 and SIRT1 by interacting with a cytoplasmic polyadenylation element. The expression profile of CPEB1 negatively correlated with overall survival in glioma patients. Overexpression of CPEB1 decreased the number of GSCs in an orthotopically implanted glioma animal model. These results suggest that CPEB1-mediated translational control is essential for the differentiation of GSCs and provides novel therapeutic concepts for differentiation therapy.

Oral hairy leukoplakia occurs on the lateral surface of the tongue that clinically as an asymptomatic white lesion. It is mainly found in patient with human immunodeficiency virus infection. However, it rarely outbreak immunosuppressed patients after organ transplantation, or the patients taking steroids or immunosuppressants. It is the result of proliferating Epstein-Barr virus in the oral epithelium. Most of human immunodeficiency virus infected patients with oral hairy leukoplakia are highly contagious and possible to progress acquired immunodeficiency syndrome. Therefore, the early diagnosis of oral hairy leukoplakia is very important. Taking a thorough history and human immunodeficiency virus screening test is highly recommended in case oral hairy leukoplakia is detected. In this case, a 29-year-old man presented with whitish lesion on lateral border of tongue is diagnosed as oral hairy leukoplakia and human immunodeficiency virus infection.

Cognitive radio systems have been considered as a strong solution of frequency scarcity due to the limit of frequency resources. This paper proposed an active interference management scheme that the secondary system can coexist with the primary system in the same frequency band without interference. Using the proposed protocol, the secondary user acquires interference channel information and transmit/receive filter information and designs precoding matrix using these information. Since interference from the secondary systems are collected to unused subchannels of the primary system, the primary system can suppress interference without additional process. The secondary systems suppress interference from the primary system using whitening matched filter so that the spectral efficiency can be improved. Numerical results provides that the proposed scheme improves performance of the secondary systems without interference to the primary system and do not degrade performance of the primary system even if the number of the secondary systems increases.

In this paper, we propose a method that estimates the channel response from underwater communication signals with MMSE (Minimun Mean Squared Error) and detects dominant components automatically based on power of response components using CFAR (Constant False Alarm Rate). Statistical characteristics are analyzed with variation of magnitude and phase and time coherence via experimental data obtained by drifting transmitter and receiver. We show that bit error rate has small difference, 1.2 times, compared with the case using every channel information estimated within data period when estimation and equalization is performed with extracted characteristic obtained by the proposed method.

Purpose We aimed to investigate the effectiveness of ferritin as a contrast agent and a potential reporter gene for tracking tumor cells or macrophages in mouse cancer models. Materials and methods Adenoviral human ferritin heavy chain (Ad-hFTH) was administrated to orthotopic glioma models and subcutaneous colon cancer mouse models using U87MG and HCT116 cells, respectively. Brain MR images were acquired before and daily for up to 6 days after the intracranial injection of Ad-hFTH. In the HCT116 tumor model, MR examinations were performed before and at 6, 24, and 48 h after intratumoral injection of Ad-hFTH, as well as before and every two days after intravenous injection of ferritin-labeled macrophages. The contrast effect of ferritin in vitro was measured by MR imaging of cell pellets. MRI examinations using a 7T MR scanner comprised a T1-weighted (T1w) spin-echo sequence, T2-weighted (T2w) relaxation enhancement sequence, and T2*-weighted (T2*w) fast low angle shot sequence. Results Cell pellet imaging of Ad-hFTH in vitro showed a strong negatively enhanced contrast in T2w and T2*w images, presenting with darker signal intensity in high concentrations of Fe. T2w images of glioma and subcutaneous HCT116 tumor models showed a dark signal intensity around or within the Ad-hFTH tumor, which was distinct with time and apparent in T2*w images. After injection of ferritin-labeled macrophages, negative contrast enhancement was identified within the tumor. Conclusion Ferritin could be a good candidate as an endogenous MR contrast agent and a potential reporter gene that is capable of maintaining cell labeling stability and cellular safety.

This paper proposes a method to realize a backflip motion for humanoid robots. In each phase of the backflip motion, the trajectory is planned. Besides, the Extended Linear Inverted Pendulum Mode (E-LIPM) is newly proposed to generate angular momentum that is needed for turning the body of the robot. In landing, an Impedance control is used to absorb the impact from the ground. Computer simulations of a backflip by a 7-DOF humanoid robot were performed, whose results show that the proposed method works well. This method is expected to be used for more complex motions of humanoid robots.

Epidermal growth factor receptor variant III (EGFRvIII) has been associated with glioma stemness, but the direct molecular mechanism linking the two is largely unknown. Here, we show that EGFRvIII induces the expression and secretion of pigment epithelium-derived factor (PEDF) via activation of signal transducer and activator of transcription 3 (STAT3), thereby promoting self-renewal and tumor progression of glioma stem cells (GSCs). Mechanistically, PEDF sustained GSC self-renewal by Notch1 cleavage, and the generated intracellular domain of Notch1 (NICD) induced the expression of Sox2 through interaction with its promoter region. Furthermore, a subpopulation with high levels of PEDF was capable of infiltration along corpus callosum. Inhibition of PEDF diminished GSC self-renewal and increased survival of orthotopic tumor-bearing mice. Together, these data indicate the novel role of PEDF as a key regulator of GSC and suggest clinical implications., A permanently activated mutant form of the epidermal growth factor receptor found in glioblastoma promotes self-renewal and tumor progression by inducing autocrine signalling via pigment epithelium-derived factor (PEDF)., Author Summary Malignant gliomas are among the most lethal types of cancer, due in part to the stem-cell-like characteristics and invasive properties of the brain tumor cells. However, little is known about the underlying molecular mechanisms that govern such processes. Here, we identify pigment epithelium-derived factor (PEDF) as a critical factor controlling stemness and tumor progression in glioma stem cells. We found that PEDF is secreted from glioblastoma expressing EGFRvIII, a frequently occurring mutation in primary glioblastoma that yields a permanently activated epidermal growth factor receptor. We delineate an EGFRvIII-STAT3-PEDF signaling axis as a signature profile of highly malignant gliomas, which promotes self-renewal of glioma stem cells. Our results demonstrate a previously unprecedented function of PEDF and implicate potential therapeutic approaches against malignant gliomas.

Hepatocyte growth factor (HGF) and its receptor, cMET, play critical roles in cell proliferation, angiogenesis and invasion in a wide variety of cancers. We therefore examined the anti-tumor activity of the humanized monoclonal anti-HGF antibody, YYB-101, in nude mice bearing human glioblastoma xenografts as a single agent or in combination with temozolomide. HGF neutralization, The extracellular signal-related kinases 1 and 2 (ERK1/2) phosphorylation, and HGF-induced scattering were assessed in HGF-expressing cell lines treated with YYB-101. To support clinical development, we also evaluated the preclinical pharmacokinetics and toxicokinetics in cynomolgus monkeys, and human and cynomolgus monkey tissue was stained with YYB-101 to test tissue cross-reactivity. We found that YYB-101 inhibited cMET activation in vitro and suppressed tumor growth in the orthotopic mouse model of human glioblastoma. Combination treatment with YYB-101 and temozolomide decreased tumor growth and increased overall survival compared with the effects of either agent alone. Five cancer-related genes (TMEM119, FST, RSPO3, ROS1 and NBL1) were overexpressed in YYB-101-treated mice that showed tumor regrowth. In the tissue cross-reactivity assay, critical cross-reactivity was not observed. The terminal elimination half-life was 21.7 days. Taken together, the in vitro and in vivo data demonstrated the anti-tumor efficacy of YYB-101, which appeared to be mediated by blocking the HGF/cMET interaction. The preclinical pharmacokinetics, toxicokinetics and tissue cross-reactivity data support the clinical development of YYB-101 for advanced cancer.

A 16.8Gbps/channel single ended transceiver for SiP based DRAM interface on silicon carrier channel is presented. A transmitter, receiver, and channel are all included in a single package. On the transmitter, 1 tap FFEs are used in 4:1 MUX and in output driver. On the receiver, source follower based CTLEs and self Vref generator are used for obtaining effective single ended signaling on Si-carrier channel. A BER that is less than 1e-12 is achieved in 65nm CMOS. The power efficiency of the transceiver is 5.9pJ/bit with 120Ω terminations at each transceiver side.

This paper proposed program voltage circuit techniques for 3D Solid State Drives (SSDs) with NAND flash memories. We reduced the charge pump stage using external high voltages of 12V and 5V with a proposed soft pre-charge high voltage switch to improve the power efficiency and area efficiency without a breakdown issue. The physical layout area in comparison with a conventional scheme and improves the power efficiency.

Heterogeneous networks have been developed to improve spectral efficiency of cellular wireless networks. Interference among heterogeneous networks decrease the spectral effeciency. In this paper, we propose a partial interference alignment in heterogeneous networks which requires only partial channel knowledge and simple computation. The proposed scheme provides interference-free communications for a macro UE which suffers from pico BSs' strong interference. Although pico UEs are still interference-limited, achievable rate loss is small since they experience weak interference. Numerical results show that the proposed scheme has a reasonable sum capacity and achievable rate compared to that of IA or CoMP-JT.

Various channel estimation methods have been proposed for shallow underwater communication channel with sparse channel type. A matching pursuit (MP), which is one of typical sparse channel estimation methods, can detect dominant components of sparse channel sequentially as a portion of matching. Mean squared error of MP, however, converges to fixed value even though signal-to-noise ratio (SNR) increases. This paper proposes a minimum mean squared error (MMSE) estimation method with constant false alarm (CFAR) detection for sparse channel estimation. Unlike MP, the mean squared error of the proposed method decreases as SNR increases and is lower than that of conventional MMSE estimators on the sparse channel. Experimental results show that the proposed method estimates sparse underwater communication channel efficiently.