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Find video protocols related to scientific articles indexed in Pubmed.
Adaptation of motor imagery EEG classification model based on tensor decomposition.
J Neural Eng
PUBLISHED: 09-22-2014
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Session-to-session nonstationarity is inherent in brain-computer interfaces based on electroencephalography. The objective of this paper is to quantify the mismatch between the training model and test data caused by nonstationarity and to adapt the model towards minimizing the mismatch.
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Longitudinal Changes in Total, 2-LTR Circular, and Integrated HIV-1 DNA During the First Year of HIV-1 Infection in CD4Low and CD4High Patient Groups with HIV-1 Subtype AE.
Viral Immunol.
PUBLISHED: 09-04-2014
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Abstract The level of viral DNA in early HIV-1 infection is an important parameter in the prediction of disease progression. Few data have been published on the dynamics of HIV-1 DNA during the first year of HIV infection. In this study, two distinct HIV-1 patient groups were enrolled. Group 1 (CD4High group) maintained their CD4 above 450 cells/?L within 1 year, while Group 2 (CD4Low group) progressed to CD4 below 300 cells/?L. The amounts of total, 2-long terminal repeat (2-LTR) circular, and integrated HIV-1 DNA were determined in the peripheral blood mononuclear cells at 1, 3, 6, and 12 months after HIV infection. Reductions in the amount of total and integrated HIV-1 DNA were detected in the CD4High group during the first year of HIV infection but not in the CD4Low group. Disease progression may be related to the body's ability to control HIV-1 DNA during early HIV-1 infection.
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Maximal likelihood correspondence estimation for face recognition across pose.
IEEE Trans Image Process
PUBLISHED: 08-28-2014
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Due to the misalignment of image features, the performance of many conventional face recognition methods degrades considerably in across pose scenario. To address this problem, many image matching-based methods are proposed to estimate semantic correspondence between faces in different poses. In this paper, we aim to solve two critical problems in previous image matching-based correspondence learning methods: 1) fail to fully exploit face specific structure information in correspondence estimation and 2) fail to learn personalized correspondence for each probe image. To this end, we first build a model, termed as morphable displacement field (MDF), to encode face specific structure information of semantic correspondence from a set of real samples of correspondences calculated from 3D face models. Then, we propose a maximal likelihood correspondence estimation (MLCE) method to learn personalized correspondence based on maximal likelihood frontal face assumption. After obtaining the semantic correspondence encoded in the learned displacement, we can synthesize virtual frontal images of the profile faces for subsequent recognition. Using linear discriminant analysis method with pixel-intensity features, state-of-the-art performance is achieved on three multipose benchmarks, i.e., CMU-PIE, FERET, and MultiPIE databases. Owe to the rational MDF regularization and the usage of novel maximal likelihood objective, the proposed MLCE method can reliably learn correspondence between faces in different poses even in complex wild environment, i.e., labeled face in the wild database.
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Role of cullin-elonginB-elonginC E3 complex in bovine immunodeficiency virus and maedi-visna virus Vif-mediated degradation of host A3Z2-Z3 proteins.
Retrovirology
PUBLISHED: 05-03-2014
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BackgroundAll lentiviruses except equine infectious anemia virus (EIVA) antagonize antiviral family APOBEC3 (A3) proteins of the host through viral Vif proteins. The mechanism by which Vif of human, simian or feline immunodeficiency viruses (HIV/SIV/FIV) suppresses the corresponding host A3s has been studied extensively.ResultsHere, we determined that bovine immunodeficiency virus (BIV) and maedi-visna virus (MVV) Vif proteins utilize the Cullin (Cul)-ElonginB (EloB)-ElonginC (EloC) complex (BIV Vif recruits Cul2, while MVV Vif recruits Cul5) to degrade Bos taurus (bt)A3Z2-Z3 and Ovis aries (oa)A3Z2-Z3, respectively, via a proteasome-dependent but a CBF-ß-independent pathway. Mutation of the BC box in BIV and MVV Vif, C-terminal hydrophilic replacement of btEloC and oaEloC and dominant-negative mutants of btCul2 and oaCul5 could disrupt the activity of BIV and MVV Vif, respectively. While the membrane-permeable zinc chelator TPEN could block BIV Vif-mediated degradation of btA3Z2-Z3, it had minimal effects on oaA3Z2-Z3 degradation induced by MVV Vif, indicating that Zn is important for the activity of BIV Vif but not MVV Vif. Furthermore, we identified a previously unreported zinc binding loop [C-x1-C-x1-H-x19-C] in the BIV Vif upstream BC box which is critical for its degradation activity.ConclusionsA novel zinc binding loop was identified in the BIV Vif protein that is important for the E3 ubiquination activity, suggesting that the degradation of btA3Z2-Z3 by BIV and that of oaA3Z2-Z3 by MVV Vif may need host factors other than CBF-ß.
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Trimeric knob protein specifically distinguishes neutralizing antibodies to different human adenovirus species: potential application for adenovirus seroepidemiology.
J. Gen. Virol.
PUBLISHED: 04-24-2014
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Adenoviruses (Ads) are non-enveloped DNA viruses that have been extensively studied and used as vectors for gene therapy and several potential vaccines. There are 57 Ad serotypes in seven species (A-G), and Ad neutralizing antibody (NAb) titres can vary by serotype and geographical location. Until now serotype- and species-specific antibodies have been detected by neutralization or haemagglutination inhibition assays. These expensive and cumbersome methods of adenovirus typing have mainly been used in epidemiological studies. Our prior work demonstrated that NAbs against the fiber protein are commonly generated during natural Ad infection in humans and the trimeric knob is preferentially recognized by fiber-induced NAbs. In this study, we expressed nine trimeric knob proteins from representative Ad serotypes of human Ad (HAdV)-A-F in Escherichia coli and found no cross-reactivity of these recombinant proteins with rabbit hyperimmune sera (among HAdV-A-F or within HAdV-C). Results of the ELISA based on Ad2 and Ad5 (both HAdV-C) knob proteins were consistent with those of neutralization assays, indicating that the trimeric knob protein would be a good candidate antigen for detecting Ad serotype-specific NAbs in sera from naturally infected subjects. We also demonstrated the primary seroepidemiology of nine Ad serotypes in 274 children using the knob-based ELISA. These results have potential implications for epidemiology of Ad serotypes and future development of Ad-based vaccines and gene therapy.
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Epitope Tags beside the N-Terminal Cytoplasmic Tail of Human BST-2 Alter Its Intracellular Trafficking and HIV-1 Restriction.
PLoS ONE
PUBLISHED: 01-01-2014
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BST-2 blocks the particle release of various enveloped viruses including HIV-1, and this antiviral activity is dependent on the topological arrangement of its four structural domains. Several functions of the cytoplasmic tail (CT) of BST-2 have been previously discussed, but the exact role of this domain remains to be clearly defined. In this study, we investigated the impact of truncation and commonly-used tags addition into the CT region of human BST-2 on its intracellular trafficking and signaling as well as its anti-HIV-1 function. The CT-truncated BST-2 exhibited potent inhibition on Vpu-defective HIV-1 and even wild-type HIV-1. However, the N-terminal HA-tagged CT-truncated BST-2 retained little antiviral activity and dramatically differed from its original protein in the cell surface level and intracellular localization. Further, we showed that the replacement of the CT domain with a hydrophobic tag altered BST-2 function possibly by preventing its normal vesicular trafficking. Notably, we demonstrated that a positive charged motif "KRXK" in the conjunctive region between the cytotail and the transmembrane domain which is conserved in primate BST-2 is important for the protein trafficking and the antiviral function. These results suggest that although the CT of BST-2 is not essential for its antiviral activity, the composition of residues in this region may play important roles in its normal trafficking which subsequently affected its function. These observations provide additional implications for the structure-function model of BST-2.
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Antitumor effect of adenoviral vector prime protein boost immunity targeting the MUC1 VNTRs.
Oncol. Rep.
PUBLISHED: 10-17-2013
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Mucin 1 (MUC1) is a tumor-associated antigen that is overexpressed in several adenocarcinomas. However, clinical trials with MUC1 showed that MUC1 is a relatively poor immunogen in humans. In view of the low immunogenicity of this protein vaccine, we designed a method based on an immunoadjuvant and immunization strategy to enhance the cellular immune response to this protein vaccine. DDA/MPL has been evaluated as an adjuvant to induce strong immunity for the tuberculosis vaccine. However, its adjuvant role combined with the vaccine targeting MUC1 in malignant carcinomas has not previously been reported. Our previous study showed that adenovirus prime protein boost vaccination could significantly enhance the cellular immunity and antitumor efficacy. In our study, we used MUC1 VNTRs as the target of cancer vaccine and DDA/MPL as the adjuvant to enhancing the cellular immunity of recombinant MUC1 protein vaccine, and an AD-9M adenoviral vector prime-recombinant protein and DDA/MPL boost (designated MUC-1 VPP vaccine) strategy was studied to enhance the antitumor efficacy. The results demonstrated that antigen-specific IFN-?-secreting T cells were increased by 2-fold, and cytotoxic T lymphocytes (CTLs) were induced effectively when the protein vaccine was combined with the DDA/MPL adjuvant. Moreover, the vaccination induced nearly 60% inhibition of the growth of B16 melanoma in mice and prolonged the survival of tumor-bearing mice. The inhibition was correlated with the specific immune responses induced by the MUC1 VPP vaccine. The data suggested that DDA/MPL-adjuvant MUC-1 VPP vaccine may be developed into effective tumor vaccines for melanomas and possibly for other tumors expressing MUC1 protein.
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Ballistocardiography with fiber optic sensor in headrest position: A feasibility study and a new processing algorithm.
Conf Proc IEEE Eng Med Biol Soc
PUBLISHED: 10-11-2013
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Ballistocardiography (BCG) is a promising unobtrusive method for home e-healthcare systems, and has attracted increasing interest in recent years along with technological advances in related biomedical, electrical engineering and computer science fields. While existing systems have investigated the efficacy of BCG setups in bed, backrest, seat or scale positions, we propose to study BCG in headrest position that will allow new practical and portable applications. To this end, we designed and implemented a multi-modality sensing system including a high-sensitivity microbend fiber optic BCG sensor. In this preliminary study, we have collected multi-modality physiological data on 3 human subjects. We ran extensive analysis on BCG in correlation with ECG, and identified special characteristics of the signal in the new BCG setup. The result suggests that new appropriate computing techniques are necessary for accurately recovering the heart beat signal. Therefore, we developed a novel algorithm for heart beat detection. We evaluate the algorithm with the data and demonstrate that it can accurately compute heart rate intervals in the headrest BCG despite significant signal distortion.
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Discriminative learning of propagation and spatial pattern for motor imagery EEG analysis.
Neural Comput
PUBLISHED: 07-29-2013
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Effective learning and recovery of relevant source brain activity patterns is a major challenge to brain-computer interface using scalp EEG. Various spatial filtering solutions have been developed. Most current methods estimate an instantaneous demixing with the assumption of uncorrelatedness of the source signals. However, recent evidence in neuroscience suggests that multiple brain regions cooperate, especially during motor imagery, a major modality of brain activity for brain-computer interface. In this sense, methods that assume uncorrelatedness of the sources become inaccurate. Therefore, we are promoting a new methodology that considers both volume conduction effect and signal propagation between multiple brain regions. Specifically, we propose a novel discriminative algorithm for joint learning of propagation and spatial pattern with an iterative optimization solution. To validate the new methodology, we conduct experiments involving 16 healthy subjects and perform numerical analysis of the proposed algorithm for EEG classification in motor imagery brain-computer interface. Results from extensive analysis validate the effectiveness of the new methodology with high statistical significance.
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Sphere Formation Assay is Not an Effective Method for Cancer Stem Cell Derivation and Characterization from the Caco-2 Colorectal Cell Line.
Curr Stem Cell Res Ther
PUBLISHED: 07-09-2013
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Although the existence of cancer stem cells (CSCs) has been demonstrated in colorectal cancer, further investigation is hindered by controversies over their surface markers. The sphere formation assay is widely used as in vitro method for derivation and characterization of CSCs based on the intrinsic self-renewal property of these cells. Isolated cancer cells that form tumorspheres are generally recognized as CSCs with self-renewal and tumorigenic capacities. In this study, colon spheres grown from Caco-2 cells in the sphere formation assay were separated from other differentiated cells and characterized. Compared with Caco-2 cells, the derived colon spheres lost several CSC properties. The colon spheres contained decreased levels of specific colorectal CSC surface markers as well as low levels of ATP-binding cassette (ABC) transporters typically overexpressed in CSCs, resulting in the near loss of their chemoresistance ability. Furthermore, cells that developed as colon spheres with strong self-renewal ability in vitro lost their tumorigenic capacity in vivo compared with Caco-2 cells, which could establish tumors in non-obese diabetic/severe-combined immunodeficient (NOD/SCID) mice. The results indicated that the Caco-2 cell derived colon spheres did not consist of colorectal CSCs. Thus, the well-accepted sphere formation assay may not be an effective method for CSC isolation and characterization from the Caco-2 colorectal cancer cell line.
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Purification of eukaryotic tetherin/Vpu proteins and detection of their interaction by ELISA.
Protein Expr. Purif.
PUBLISHED: 05-15-2013
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Tetherin/BST-2/CD317 inhibits HIV-1 release from infected cells, while HIV-1 Vpu efficiently antagonizes tetherin based on intermolecular interactions between the transmembrane domains of each protein. In this study, we successfully partially purified His-tagged tetherin with a glycophosphatidylinositol deletion (delGPI) and His-tagged full-length Vpu from transiently transfected 293T cells using affinity chromatography. The in vitro interaction between these purified proteins was observed by a pull-down assay and ELISA. Detection of the Vpu/tetherin interaction by ELISA is a novel approach that would be advantageous for inhibitor screening in vitro. Successful co-purification of the tetherin/Vpu complex also provides a basis for further structural studies.
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Dynamically weighted ensemble classification for non-stationary EEG processing.
J Neural Eng
PUBLISHED: 04-10-2013
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The non-stationary nature of EEG poses a major challenge to robust operation of brain-computer interfaces (BCIs). The objective of this paper is to propose and investigate a computational method to address non-stationarity in EEG classification.
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Folic acid stimulates proliferation of transplanted neural stem cells after focal cerebral ischemia in rats.
J. Nutr. Biochem.
PUBLISHED: 04-09-2013
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Folic acid (FA) stimulates neural stem cell (NSC) proliferation in vitro and enhances hippocampal neurogenesis in rats after middle cerebral artery occlusion (MCAO). The effect of FA supplementation on exogenous NSCs transplanted in MCAO rats was observed to determine if FA can stimulate NSC replacement after focal cerebral ischemia. Rats were randomly assigned to 3 groups: MCAO; MCAO and exogenous NSC transplantation (MCAO+NSCs); and MCAO, NSC transplantation and FA (MCAO+NSCs+FA). FA (0.8 mg/kg) or vehicle was administered by gavage daily for 28 days before MCAO and 23 days afterward. NSCs were labeled with superparamagnetic iron oxide (SPIO) and bromodeoxyuridine (BrdU) prior to transplantation into the striatum, contralateral to the ischemic zone, at 2 days post-MCAO. Magnetic resonance imaging tracking and fluorescent immunohistochemistry, as well as measurement of serum folate concentration, were performed at intervals up to 21 days after transplantation. FA supplementation caused sustained increases of 400-600% in serum folate concentration. Magnetic resonance images indicated that SPIO-labeled NSCs were more abundant at the transplantation and ischemic brain sites in MCAO+NSCs+FA rats than in MCAO+NSCs rats. Similarly, immunohistochemistry showed that the numbers of Sox-2/BrdU double positive cells at the transplantation and ischemic sites were higher in the rats that received FA. In conclusion, after focal cerebral ischemia, FA supplementation stimulates transplanted NSCs to proliferate and migrate to ischemic sites.
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Overexpression of clusterin promotes angiogenesis via the vascular endothelial growth factor in primary ovarian cancer.
Mol Med Rep
PUBLISHED: 04-08-2013
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Clusterin (CLU), a multifunctional glycoprotein, is ubiquitously produced in mammalian tissues. CLU has been shown to play significant roles in many of the biological behaviours of human tumors, such as cell proliferation, apoptosis, chemoresistance and angiogenesis. However, the relationship of CLU expression with angiogenesis in ovarian cancer has not been studied. A total of 275 epithelial ovarian tumors were obtained from archives of paraffin?embedded tissues. Immunohistochemical (IHC) staining for CLU and vascular endothelial growth factor (VEGF) was performed on a tissue microarray (TMA) including 181 primary ovarian epithelial cancer, 40 borderline ovarian tumors and 54 ovarian cancer mesenteric metastasis samples. Of the 174 cases, overexpression of CLU and VEGF were detected in 107 (61.5%) and 109 (62.9%) cases of primary ovarian carcinoma, respectively. Of the 107 cases of primary ovarian carcinoma with overexpression of CLU, expression of VEGF was increased in 82 (75.2%) cases. However, in another 67 cases without CLU overexpression, overexpression of VEGF was observed in only 27 (24.8%) cases (P<0.05). Overexpression of CLU in epithelial ovarian cancer appears to be correlated with increased tumor angiogenesis, consistent with the established role of CLU as an oncogene in the biology of ovarian cancer. In the treatment of ovarian cancer, these two markers may be used in the selection of patients for targeted therapy.
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Short-Form CDYLb but not long-form CDYLa functions cooperatively with histone methyltransferase G9a in hepatocellular carcinomas.
Genes Chromosomes Cancer
PUBLISHED: 03-14-2013
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In hepatocellular carcinomas (HCCs), the levels of histone H3 dimethylation at lysine 9 (H3K9me2) and its corresponding histone methyltransferase G9a are significantly elevated. Recently, G9a was reported to form a complex with the H3K9 methylation effector protein CDYL, but little is known about the expression of CDYL in HCC patients. The human CDYL gene produces two transcripts, a long form (CDYLa) and a short form (CDYLb), but it is unclear whether the protein products have different functions. The aim of this study was to investigate the distinctions between CDYLa and CDYLb and their expression levels in HCC tissues. We first examined binding abilities of the different CDYL forms with methylated H3 peptides by a pull-down assay. Human CDYLb (h-CDYLb) specifically recognized H3Kc9me2 and H3Kc9me3 modifications, whereas human CDYLa (h-CDYLa) did not interact with any methylated H3 peptides. Similarly, mouse CDYLb (m-CDYLb) specifically bound with di- and tri-methylated H3Kc9 peptides, while mouse CDYLa (m-CDYLa) lacked that ability. Affinity purification also was used to identify the distinct composition of the h-CDYLa or h-CDYLb protein complex. h-CDYLb was found in a multiprotein complex with G9a and GLP, while the h-CDYLa complex did not contain these two enzymes. Consistent with the protein complex composition, h-CDYLb and G9a were both upregulated in HCC tissues, compared with adjacent non-cancerous liver tissues. Furthermore, the positive correlation between expression levels of h-CDYLb and G9a was statistically significant. In contrast, h-CDYLa showed no enrichment in HCC tissues. These findings suggest that h-CDYLb and G9a are cooperatively involved in HCC.
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Interactions between HIV-1 Vif and human ElonginB-ElonginC are important for CBF-? binding to Vif.
Retrovirology
PUBLISHED: 03-04-2013
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The HIV-1 accessory factor Vif is necessary for efficient viral infection in non-permissive cells. Vif antagonizes the antiviral activity of human cytidine deaminase APOBEC3 proteins that confer the non-permissive phenotype by tethering them (APOBEC3DE/3F/3G) to the Vif-CBF-?-ElonginB-ElonginC-Cullin5-Rbx (Vif-CBF-?-EloB-EloC-Cul5-Rbx) E3 complex to induce their proteasomal degradation. EloB and EloC were initially reported as positive regulatory subunits of the Elongin (SIII) complex. Thereafter, EloB and EloC were found to be components of Cul-E3 complexes, contributing to proteasomal degradation of specific substrates. CBF-? is a newly identified key regulator of Vif function, and more information is needed to further clarify its regulatory mechanism. Here, we comprehensively investigated the functions of EloB (together with EloC) in the Vif-CBF-?-Cul5 E3 ligase complex.
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Characteristics of neutralizing antibodies to adenovirus capsid proteins in human and animal sera.
Virology
PUBLISHED: 01-23-2013
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Although it is known that Ad5-specific neutralizing antibodies (NAbs) against three major viral capsid components (hexon, penton and fiber) are generated, differences in the frequency and nature of these pre-existing NAbs remain unclear. The results emphasized the contribution of anti-fiber antibodies to Ad5 neutralization responses generated during natural viral infection. Additionally, Ad5-specific NAbs against the fiber knob protein were present in over 90% of the positive serum samples while 42% of the sera had NAbs against hexon in this study based on neutralization assay of anti-HVR and anti-knob subtracted sera and Western blotting analysis. We also found that the trimeric knob was preferentially recognized by fiber-induced NAbs and it was serotype-specific in human adenovirus species C. Results indicated that the trimeric knob protein would be a good candidate antigen for detecting adenovirus serotype-specific NAbs in naturally infected sera.
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A brain-computer interface based cognitive training system for healthy elderly: a randomized control pilot study for usability and preliminary efficacy.
PLoS ONE
PUBLISHED: 01-01-2013
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Cognitive decline in aging is a pressing issue associated with significant healthcare costs and deterioration in quality of life. Previously, we reported the successful use of a novel brain-computer interface (BCI) training system in improving symptoms of attention deficit hyperactivity disorder. Here, we examine the feasibility of the BCI system with a new game that incorporates memory training in improving memory and attention in a pilot sample of healthy elderly. This study investigates the safety, usability and acceptability of our BCI system to elderly, and obtains an efficacy estimate to warrant a phase III trial. Thirty-one healthy elderly were randomized into intervention (n?=?15) and waitlist control arms (n?=?16). Intervention consisted of an 8-week training comprising 24 half-hour sessions. A usability and acceptability questionnaire was administered at the end of training. Safety was investigated by querying users about adverse events after every session. Efficacy of the system was measured by the change of total score from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) before and after training. Feedback on the usability and acceptability questionnaire was positive. No adverse events were reported for all participants across all sessions. Though the median difference in the RBANS change scores between arms was not statistically significant, an effect size of 0.6SD was obtained, which reflects potential clinical utility according to Simons randomized phase II trial design. Pooled data from both arms also showed that the median change in total scores pre and post-training was statistically significant (Mdn?=?4.0; p<0.001). Specifically, there were significant improvements in immediate memory (p?=?0.038), visuospatial/constructional (p?=?0.014), attention (p?=?0.039), and delayed memory (p<0.001) scores. Our BCI-based system shows promise in improving memory and attention in healthy elderly, and appears to be safe, user-friendly and acceptable to senior users. Given the efficacy signal, a phase III trial is warranted.
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A large clinical study on the ability of stroke patients to use an EEG-based motor imagery brain-computer interface.
Clin EEG Neurosci
PUBLISHED: 12-30-2011
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Brain-computer interface (BCI) technology has the prospects of helping stroke survivors by enabling the interaction with their environ ment through brain signals rather than through muscles, and restoring motor function by inducing activity-dependent brain plasticity. This paper presents a clinical study on the extent of detectable brain signals from a large population of stroke patients in using EEG-based motor imagery BCI. EEG data were collected from 54 stroke patients whereby finger tapping and motor imagery of the stroke-affected hand were performed by 8 and 46 patients, respectively. EEG data from 11 patients who gave further consent to perform motor imagery were also collected for second calibration and third independent test sessions conducted on separate days. Off-line accuracies of classifying the two classes of EEG from finger tapping or motor imagery of the stroke-affected hand versus the EEG from background rest were then assessed and compared to 16 healthy subjects. The mean off-line accuracy of detecting motor imagery by the 46 patients (mu=0.74) was significantly lower than finger tapping by 8 patients (mu=0.87, p=0.008), but not significantly lower than motor imagery by healthy subjects (mu=0.78, p=0.23). Six stroke patients performed motor imagery at chance level, and no correlation was found between the accuracies of detecting motor imagery and their motor impairment in terms of Fugl-Meyer Assessment (p=0.29). The off-line accuracies of the 11 patients in the second session (mu=0.76) were not significantly different from the first session (mu=0.72, p=0.16), or from the on-line accuracies of the third independent test session (mu=0.82, p=0.14). Hence this study showed that the majority of stroke patients could use EEG-based motor imagery BCI.
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Learning from feedback training data at a self-paced brain-computer interface.
J Neural Eng
PUBLISHED: 07-19-2011
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Inherent changes that appear in brain signals when transferring from calibration to feedback sessions are a challenging but critical issue in brain-computer interface (BCI) applications. While previous studies have mostly focused on the adaptation of classifiers, in this paper we study the feasibility and the importance of the adaptation of feature extraction in a self-paced BCI paradigm. First, we conduct calibration and feedback training on able-bodied naïve subjects using a new self-paced motor imagery BCI including the idle state. The online results suggest that the feature space constructed from calibration data may become ineffective during feedback sessions. Hence, we propose a new supervised method that learns from a feedback session to construct a more appropriate feature space, on the basis of the maximum mutual information principle between feedback signal, target signal and EEG. Specifically, we formulate the learning objective as maximizing a kernel-based mutual information estimate with respect to the spatial-spectral filtering parameters. We then derive a gradient-based optimization algorithm for the learning task. An experimental study is conducted using offline simulation. The results show that the proposed method is able to construct effective feature spaces to capture the discriminative information in feedback training data and, consequently, the prediction error can be significantly reduced using the new features.
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Obesity and hepatosteatosis in mice with enhanced oxidative DNA damage processing in mitochondria.
Am. J. Pathol.
PUBLISHED: 03-26-2011
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Mitochondria play critical roles in oxidative phosphorylation and energy metabolism. Increasing evidence supports that mitochondrial DNA (mtDNA) damage and dysfunction play vital roles in the development of many mitochondria-related diseases, such as obesity, diabetes mellitus, infertility, neurodegenerative disorders, and malignant tumors in humans. Human 8-oxoguanine-DNA glycosylase 1 (hOGG1) transgenic (TG) mice were produced by nuclear microinjection. Transgene integration was analyzed by PCR. Transgene expression was measured by RT-PCR and Western blot analysis. Mitochondrial DNA damage was analyzed by mutational analyses and measurement of mtDNA copy number. Total fat content was measured by a whole-body scan using dual-energy X-ray absorptiometry. The hOGG1 overexpression in mitochondria increased the abundance of intracellular free radicals and major deletions in mtDNA. Obesity in hOGG1 TG mice resulted from increased fat content in tissues, produced by hyperphagia. The molecular mechanisms of obesity involved overexpression of genes in the central orexigenic (appetite-stimulating) pathway, peripheral lipogenesis, down-regulation of genes in the central anorexigenic (appetite-suppressing) pathway, peripheral adaptive thermogenesis, and fatty acid oxidation. Diffuse hepatosteatosis, female infertility, and increased frequency of malignant lymphoma were also seen in these hOGG1 TG mice. High levels of hOGG1 expression in mitochondria, resulting in enhanced oxidative DNA damage processing, may be an important factor in human metabolic syndrome, infertility, and malignancy.
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Distinct epigenetic profiling in head and neck squamous cell carcinoma stem cells.
Otolaryngol Head Neck Surg
PUBLISHED: 02-18-2011
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To identify unique epigenetic signature in cancer stem cells (CSCs) in head and neck squamous cell carcinoma (HNSCC).
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Optimum spatio-spectral filtering network for brain-computer interface.
IEEE Trans Neural Netw
PUBLISHED: 01-11-2011
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This paper proposes a feature extraction method for motor imagery brain-computer interface (BCI) using electroencephalogram. We consider the primary neurophysiologic phenomenon of motor imagery, termed event-related desynchronization, and formulate the learning task for feature extraction as maximizing the mutual information between the spatio-spectral filtering parameters and the class labels. After introducing a nonparametric estimate of mutual information, a gradient-based learning algorithm is devised to efficiently optimize the spatial filters in conjunction with a band-pass filter. The proposed method is compared with two existing methods on real data: a BCI Competition IV dataset as well as our data collected from seven human subjects. The results indicate the superior performance of the method for motor imagery classification, as it produced higher classification accuracy with statistical significance ( ? 95% confidence level) in most cases.
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A hybrid BCI system for 2-D asynchronous cursor control.
Conf Proc IEEE Eng Med Biol Soc
PUBLISHED: 11-25-2010
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In this paper, a hybrid EEG-based brain computer interface (BCI) is designed for two-dimensional cursor control. In our approach, two brain activity patterns, i.e., motor imagery and P300 potential, are used for controlling the horizontal and the vertical movements of the cursor respectively. A real-time BCI system based on this approach is implemented and evaluated through an online experiment. Six subjects attending this experiment can perform 2-D cursor control effectively. Our experimental results show that the system has the following merits compared with prior systems: 1) it does not rely on intensive user training; 2) it allows cursor movement between arbitrary positions.
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Clinical study of neurorehabilitation in stroke using EEG-based motor imagery brain-computer interface with robotic feedback.
Conf Proc IEEE Eng Med Biol Soc
PUBLISHED: 11-25-2010
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This clinical study investigates the ability of hemiparetic stroke patients in operating EEG-based motor imagery brain-computer interface (MI-BCI). It also assesses the efficacy in motor improvements on the stroke-affected upper limb using EEG-based MI-BCI with robotic feedback neurorehabilitation compared to robotic rehabilitation that delivers movement therapy. 54 hemiparetic stroke patients with mean age of 51.8 and baseline Fugl-Meyer Assessment (FMA) 14.9 (out of 66, higher = better) were recruited. Results showed that 48 subjects (89%) operated EEG-based MI-BCI better than at chance level, and their ability to operate EEG-based MI-BCI is not correlated to their baseline FMA (r=0.358). Those subjects who gave consent are randomly assigned to each group (N=11 and 14) for 12 1-hour rehabilitation sessions for 4 weeks. Significant gains in FMA scores were observed in both groups at post-rehabilitation (4.5, 6.2; p=0.032, 0.003) and 2-month post-rehabilitation (5.3, 7.3; p=0.020, 0.013), but no significant differences were observed between groups (p=0.512, 0.550). Hence, this study showed evidences that a majority of hemiparetic stroke patients can operate EEG-based MI-BCI, and that EEG-based MI-BCI with robotic feedback neurorehabilitation is effective in restoring upper extremities motor function in stroke.
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N-terminal deletion effects of human survivin on dimerization and binding to Smac/DIABLO in vitro.
J Phys Chem B
PUBLISHED: 11-09-2010
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Survivin, as an apoptosis suppressor, exists as a homodimer interfacing at the N-terminal portion (residues 6-13) of its baculovirus IAP repeat (BIR) domain and a linker segment (residues 89-102). Here we expressed full-length human Survivin (SurF) and a series of its mutants, Sur?N7, Sur?N13, and Sur?N18 with significant truncations of the N-terminus, all of which could still dimerize in solution. Single-molecule force spectroscopy (SMFS) was used to quantitate the unbinding forces of full-length and the mutant homodimers and revealed that the N-terminal residues up to Arg18 were not essential for dimerization. Meanwhile, the binding of Sur?N7 to Smac/DIABLO determined by ELISA was as efficient as the wild-type, but that of Sur?N13 was significantly reduced, and that of Sur?N18 was completely lost. Together, these findings provide direct evidence that the N-terminal sequence of Survivin is not critical for dimer formation but may contribute to correct folding and function of BIR.
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A maximum mutual information approach for constructing a 1D continuous control signal at a self-paced brain-computer interface.
J Neural Eng
PUBLISHED: 09-14-2010
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This paper addresses an important issue in a self-paced brain-computer interface (BCI): constructing subject-specific continuous control signal. To this end, we propose an alternative to the conventional regression/classification-based mechanism for building the transformation from EEG features into a univariate control signal. Based on information theory, the mechanism formulates the optimum transformation as maximizing the mutual information between the control signal and the mental state. We introduce a non-parametric mutual information estimate for general output distribution, and then develop a gradient-based algorithm to optimize the transformation using training data. We conduct an offline simulation study using motor imagery data from the BCI Competition IV Data Set I. The results show that the learning algorithm converged quickly, and the proposed method yielded significantly higher BCI performance than the conventional mechanism.
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Optimization of electroporation conditions for Arthrobacter with plasmid PART2.
J. Microbiol. Methods
PUBLISHED: 09-08-2010
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A prerequisite for genetic studies of Arthrobacter is a high efficiency transformation system that allows for DNA transfer, transposon mutagenesis, and expression of specific genes. In this study, we develop a detailed electroporation method through a systematic examination of the factors involved in the entire electroporation process. Key features of this procedure, including the addition of penicillin to cells during the early log phase of growth and the presence of 0.5M sorbitol in the electroporation and recovery media, produced the greatest increases in transformation efficiency and consistency of results. The transformation rate also varied depending on the electrical parameters, DNA concentration, and recovery time period. Using optimum conditions, we generally achieved an efficiency of 6.8 × 10(7) transformants per microgram of PART2 for Arthrobacter sp. A3. This protocol was also successfully applied to other Arthrobacter species. Therefore, we conclude that the proposed method is rapid, simple and convenient, which allows a transformation trial to be accomplished in minutes.
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Effect of lumbar angular motion on central canal diameter: positional MRI study in 491 cases.
Chin. Med. J.
PUBLISHED: 09-08-2010
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Lumbar spinal stenosis is a common problem that is receiving attention with the advent of novel treatment procedures. Prior positional MRI studies demonstrated lumbar canal diameter changes with flexion and extension. There have not been any studies to examine the amount of spinal canal diameter change relative to the amount of angular motion. The purpose of this study was to evaluate the correlation between the lumbar canal diameter change and the angular motion quantitatively.
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An EEG-based BCI system for 2-D cursor control by combining Mu/Beta rhythm and P300 potential.
IEEE Trans Biomed Eng
PUBLISHED: 07-08-2010
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Two-dimensional cursor control is an important and challenging issue in EEG-based brain-computer interfaces (BCIs). To address this issue, here we propose a new approach by combining two brain signals including Mu/Beta rhythm during motor imagery and P300 potential. In particular, a motor imagery detection mechanism and a P300 potential detection mechanism are devised and integrated such that the user is able to use the two signals to control, respectively, simultaneously, and independently, the horizontal and the vertical movements of the cursor in a specially designed graphic user interface. A real-time BCI system based on this approach is implemented and evaluated through an online experiment involving six subjects performing 2-D control tasks. The results attest to the efficacy of obtaining two independent control signals by the proposed approach. Furthermore, the results show that the system has merit compared with prior systems: it allows cursor movement between arbitrary positions.
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Effectiveness of a brain-computer interface based programme for the treatment of ADHD: a pilot study.
Psychopharmacol Bull
PUBLISHED: 06-29-2010
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Majority of children with attention deficit hyperactivity disorder (ADHD) have significant inattentive symptoms. We developed a progressive series of activities involving brain-computer interface-based games which could train users to improve their concentration. This pilot study investigated if the intervention could be utilized in children and if it could improve inattentive symptoms of ADHD. Ten medication-naive children aged 7 to 12 diagnosed with ADHD (combined or inattentive subtypes) received 20 sessions of therapy over a 10-week period. They were compared with age- and gendermatched controls. Both parent and teacher-rated inattentive score on the ADHD Rating Scale-IV improved more in the intervention group. A larger scale trial is warranted to further investigate the efficacy of our treatment programme in treating ADHD.
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A brain controlled wheelchair to navigate in familiar environments.
IEEE Trans Neural Syst Rehabil Eng
PUBLISHED: 05-10-2010
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While brain-computer interfaces (BCIs) can provide communication to people who are locked-in, they suffer from a very low information transfer rate. Further, using a BCI requires a concentration effort and using it continuously can be tiring. The brain controlled wheelchair (BCW) described in this paper aims at providing mobility to BCI users despite these limitations, in a safe and efficient way. Using a slow but reliable P300 based BCI, the user selects a destination amongst a list of predefined locations. While the wheelchair moves on virtual guiding paths ensuring smooth, safe, and predictable trajectories, the user can stop the wheelchair by using a faster BCI. Experiments with nondisabled subjects demonstrated the efficiency of this strategy. Brain control was not affected when the wheelchair was in motion, and the BCW enabled the users to move to various locations in less time and with significantly less control effort than other control strategies proposed in the literature.
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Genetic alterations in papillary thyroid carcinoma and hashimoto thyroiditis: An analysis of hOGG1 loss of heterozygosity.
Arch. Otolaryngol. Head Neck Surg.
PUBLISHED: 03-17-2010
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To determine the relationship between hOGG1 loss of heterozygosity (LOH), Hashimoto thyroiditis (HT), and papillary thyroid cancer (PTC). Hashimoto thyroiditis is an autoimmune mediated chronic inflammatory disease previously shown to coexist with papillary PTC. To further define the relationship between HT and PTC, we report an analysis of hOGG1, a major repair gene for free radical-induced oxidative DNA damages, in thyroidectomy specimens.
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A clinical study of motor imagery-based brain-computer interface for upper limb robotic rehabilitation.
Conf Proc IEEE Eng Med Biol Soc
PUBLISHED: 12-08-2009
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Non-invasive EEG-based motor imagery brain-computer interface (MI-BCI) holds promise to effectively restore motor control to stroke survivors. This clinical study investigates the effects of MI-BCI for upper limb robotic rehabilitation compared to standard robotic rehabilitation. The subjects are hemiparetic stroke patients with mean age of 50.2 and baseline Fugl-Meyer (FM) score 29.7 (out of 66, higher = better) randomly assigned to each group respectively (N = 8 and 10). Each subject underwent 12 sessions of 1-hour rehabilitation for 4 weeks. Significant gains in FM scores were observed in both groups at post-rehabilitation (4.9, p = 0.001) and 2-month post-rehabilitation (4.9, p = 0.002). The experimental group yielded higher 2-month post-rehabilitation gain than the control (6.0 versus 4.0) but no significance was found (p = 0.475). However, among subjects with positive gain (N = 6 and 7), the initial difference of 2.8 between the two groups was increased to a significant 6.5 (p = 0.019) after adjustment for age and gender. Hence this study provides evidence that BCI-driven robotic rehabilitation is effective in restoring motor control for stroke.
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Spatio-spectral feature selection based on robust mutual information estimate for Brain Computer Interfaces.
Conf Proc IEEE Eng Med Biol Soc
PUBLISHED: 12-08-2009
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This paper addresses the issue of selecting optimal spatio-spectral features, which is key to high performance motor imagery (MI) classification that is in turn one of the central topics in EEG-based brain computer interfaces. In particular, this work proposes a novel method which first formulates the selection of features as maximizing mutual information between class labels and features. It then uses a robust estimate of mutual information, within a filter-bank and common spatial pattern feature extraction framework, to select an effective feature set. We have assessed the proposed method on both BCI Competition IV Set I and a separate data set collected in our lab from 7 healthy subjects. The results indicate the method is effective in selecting optimal spatial-spectral features for classification.
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Robust filter bank common spatial pattern (RFBCSP) in motor-imagery-based brain-computer interface.
Conf Proc IEEE Eng Med Biol Soc
PUBLISHED: 12-08-2009
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The Filter Bank Common Spatial Pattern (FBCSP) algorithm performs autonomous selection of key temporal-spatial discriminative EEG characteristics in motor imagery-based Brain Computer Interfaces (MI-BCI). However, FBCSP is sensitive to outliers because it involves multiple estimations of covariance matrices from EEG measurements. This paper proposes a Robust FBCSP (RFBCSP) algorithm whereby the estimates of the covariance matrices are replaced with the robust Minimum Covariance Determinant (MCD) estimator. The performance of RFBCSP is investigated on a publicly available dataset and compared against FBCSP using 10x10-fold cross-validation accuracies on training data, and session-to-session transfer kappa values on independent test data. The results showed that RFBCSP yielded improvements in certain subjects and slight improvement in overall performance across subjects. Analysis on one subject who improved suggested that outliers were excluded from the robust covariance matrices estimation. These results revealed a promising direction of RFBCSP for robust classifications of EEG measurements in MI-BCI.
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Multi-class filter bank common spatial pattern for four-class motor imagery BCI.
Conf Proc IEEE Eng Med Biol Soc
PUBLISHED: 12-08-2009
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This paper investigates the classification of multi-class motor imagery for electroencephalogram (EEG)-based Brain-Computer Interface (BCI) using the Filter Bank Common Spatial Pattern (FBCSP) algorithm. The FBCSP algorithm classifies EEG measurements from features constructed using subject-specific temporal-spatial filters. However, the FBCSP algorithm is limited to binary-class motor imagery. Hence, this paper proposes 3 approaches of multi-class extension to the FBCSP algorithm: One-versus-Rest, Pair-Wise and Divide-and-Conquer. These approaches decompose the multi-class problem into several binary-class problems. The study is conducted on the BCI Competition IV dataset IIa, which comprises single-trial EEG data from 9 subjects performing 4-class motor imagery of left-hand, right-hand, foot and tongue actions. The results showed that the multi-class FBCSP algorithm could extract features that matched neurophysiological knowledge, and yielded the best performance on the evaluation data compared to other international submissions.
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Increased microsatellite instability and epigenetic inactivation of the hMLH1 gene in head and neck squamous cell carcinoma.
Otolaryngol Head Neck Surg
PUBLISHED: 04-28-2009
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The study is designed to elucidate the relationship between epigenetic silencing of the hMLH1 (human MutL homologue 1) gene and microsatellite instability (MSI) and the prognostic values of hMLH1 promoter methylation and MSI in head and neck squamous cell carcinoma (HNSCC).
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Unsupervised brain computer interface based on intersubject information and online adaptation.
IEEE Trans Neural Syst Rehabil Eng
PUBLISHED: 02-18-2009
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Conventional brain computer interfaces rely on a guided calibration procedure to address the problem of considerable variations in electroencephalography (EEG) across human subjects. This calibration, however, implies inconvenience to the end users. In this paper, we propose an online-adaptive-learning method to address this problem for P300-based brain computer interfaces. By automatically capturing subject-specific EEG characteristics during online operation, this method allows a new user to start operating a P300-based brain-computer interface without guided (supervised) calibration. The basic principle is to first learn a generic model termed subject-independent model offline from EEG of a pool of subjects to capture common P300 characteristics. For a new user, a new model termed subject-specific model is then adapted online based on EEG recorded from the new subject and the corresponding labels predicted by either the subject-independent model or the adapted subject-specific model, depending on a confidence score. To verify the proposed method, a study involving 10 healthy subjects is carried out and positive results are obtained. For instance, after 2-4 min online adaptation (spelling of 10-20 characters), the accuracy of the adapted model converges to that of a fully trained supervised subject-specific model.
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Epigenetic and immunohistochemical characterization of the Clusterin gene in ovarian tumors.
Arch. Gynecol. Obstet.
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To characterize abnormal epigenetic changes and protein expression of the clusterin gene in a large series of ovarian malignant and borderline tumors.
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Overexpression of inactive tetherin delGPI mutant inhibits HIV-1 Vpu-mediated antagonism of endogenous tetherin.
FEBS Lett.
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Tetherin/BST-2/CD317 inhibits HIV-1 release from infected cells, but the viral Vpu protein efficiently antagonizes this antiviral activity through direct interaction between the transmembrane (TM) domains of each protein. Here, we demonstrated that overexpression of an inactive tetherin delGPI mutant, the TM domain of which could competitively block Vpu targeting of endogenous tetherin, potently inhibited HIV-1 release from human tetherin-positive cells in both transient and stable expression conditions. These results also suggest that heterologous dimerization occurred between the delGPI mutant and endogenous tetherin. These findings suggest that blocking the Vpu/tetherin interface may be a novel therapeutic approach against HIV-1 release.
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A brain-computer interface based attention training program for treating attention deficit hyperactivity disorder.
PLoS ONE
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Attention deficit hyperactivity disorder (ADHD) symptoms can be difficult to treat. We previously reported that a 20-session brain-computer interface (BCI) attention training programme improved ADHD symptoms. Here, we investigated a new more intensive BCI-based attention training game system on 20 unmedicated ADHD children (16 males, 4 females) with significant inattentive symptoms (combined and inattentive ADHD subtypes). This new system monitored attention through a head band with dry EEG sensors, which was used to drive a feed forward game. The system was calibrated for each user by measuring the EEG parameters during a Stroop task. Treatment consisted of an 8-week training comprising 24 sessions followed by 3 once-monthly booster training sessions. Following intervention, both parent-rated inattentive and hyperactive-impulsive symptoms on the ADHD Rating Scale showed significant improvement. At week 8, the mean improvement was -4.6 (5.9) and -4.7 (5.6) respectively for inattentive symptoms and hyperactive-impulsive symptoms (both p<0.01). Cohens d effect size for inattentive symptoms was large at 0.78 at week 8 and 0.84 at week 24 (post-boosters). Further analysis showed that the change in the EEG based BCI ADHD severity measure correlated with the change ADHD Rating Scale scores. The BCI-based attention training game system is a potential new treatment for ADHD.
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Production of influenza H1N1 vaccine from MDCK cells using a novel disposable packed-bed bioreactor.
Appl. Microbiol. Biotechnol.
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A process for human influenza H1N1 virus vaccine production from Madin-Darby canine kidney (MDCK) cells using a novel packed-bed bioreactor is described in this report. The mini-bioreactor was used to study the relationship between cell density and glucose consumption rate and to optimize the infection parameters of the influenza H1N1 virus (A/New Caledonia/20/99). The MDCK cell culture and virus infection were then monitored in a disposable perfusion bioreactor (AmProtein Current Perfusion Bioreactor) with proportional-integral-derivative control of pH, dissolved O(2) (DO), agitation, and temperature. During 6 days of culture, the total cell number increased from 2.0?×?10(9) to 3.2?×?10(10) cells. The maximum virus titers of 768 hemagglutinin units/100 ?L and 7.8?×?10(7) 50 % tissue culture infectious doses/mL were obtained 3 days after infection. These results demonstrate that using a disposable perfusion bioreactor for large-scale cultivation of MDCK cells, which allows for the control of DO, pH, and other conditions, is a convenient and stable platform for industrial-scale production of influenza vaccines.
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Not all side population cells contain cancer stem-like cells in human gastric cancer cell lines.
Dig. Dis. Sci.
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Side population (SP) cells may play a crucial role in tumorigenesis and the recurrence of cancer. Many kinds of cell lines and tissue have demonstrated presence of SP cells including different gastric cancer cell lines. However, is that true all SP cells contain cancer stem-like cells in gastric cancer cell lines?
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DNA and adenovirus tumor vaccine expressing truncated survivin generates specific immune responses and anti-tumor effects in a murine melanoma model.
Cancer Immunol. Immunother.
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Survivin is overexpressed in major types of cancer and is considered an ideal "universal" tumor-associated antigen that can be targeted by immunotherapeutic vaccines. However, its anti-apoptosis function raises certain safety concerns. Here, a new truncated human survivin, devoid of the anti-apoptosis function, was generated as a candidate tumor vaccine. Interleukin 2 (IL-2) has been widely used as an adjuvant for vaccination against various diseases. Meanwhile, the DNA prime and recombinant adenovirus (rAd) boost heterologous immunization strategy has been proven to be highly effective in enhancing immune responses. Therefore, the efficacy of a new cancer vaccine based on a truncated form of survivin, combined with IL-2, DNA prime, and rAd boost, was tested. As prophylaxis, immunization with the DNA vaccine alone resulted in a weak immune response and modest anti-tumor effect, whereas the tumor inhibition ratio with the DNA vaccine administered with IL-2 increased to 89 % and was further increased to nearly 100 % by rAd boosting. Moreover, complete tumor rejection was observed in 5 of 15 mice. Efficacy of the vaccine administered therapeutically was enhanced by nearly 300 % when combined with carboplatin. These results indicated that vaccination with a truncated survivin vaccine using DNA prime-rAd boost combined with IL-2 adjuvant and carboplatin represents an attractive strategy to overcoming immune tolerance to tumors and has potential therapeutic benefits in melanoma cancer.
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Investigation of transport mechanism of exendin-4 across Madin Darby canine kidney cell monolayers.
Biol. Pharm. Bull.
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The purpose of this study was to investigate the transport mechanism of exendin-4 using Madin Darby canine kidney (MDCK) cell monolayer as an in vitro model of the human intestinal barrier. The roles of active and passive mechanisms of exendin-4 in the cell models were well studied and the corresponding contributions of the transcelluar and paracellular pathway to exendin-4 transport were also evaluated. Moreover, the apparent permeability coefficient (P(app)) values of exendin-4 were determined in the presence of chitosan, sodium decanoate and ethylenediaminetetraacetic acid (EDTA) to further confirm the relative transport mechanism and to evaluate their potential utility in future formulation design. The results revealed the low transport capacity of exendin-4 (P(app), 0.10±0.06×10(-6) cm/s). And exendin-4 transport across the cell models was time and concentration-dependence, direction and energy-independence, and similar to the passive transport marker. Drug efflux and active transport were not observed. In the presence of absorption enhancers, the P(app) value significantly increased up to 2.2-11.9 folds without apparent cytotoxicity, which is comparable to that of the paracellular transport marker. And the order of enhancement was to the effect of chitosan>EDTA>sodium decanoate, and the order of safety was sodium decanoate?chitosan>EDTA. These findings demonstrated that exendin-4 transport across MDCK cell monolayer mainly by passive paracellular pathway, which agrees with the result of confocal laser scanning microscopy. And these absorption enhancers can be used as potential safe ingredients to improve oral efficacy of exendin-4.
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MicroRNA-1 and microRNA-499 downregulate the expression of the ets1 proto-oncogene in HepG2 cells.
Oncol. Rep.
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MicroRNAs may function to promote or suppress tumor development, depending on the cellular context. The important role of microRNAs in regulating molecular pathways underlying tumorigenesis has been emphasized in hepatocellular carcinoma (HCC). MicroRNAs regulate gene expression via post-transcriptional mechanisms by inhibiting translation or by degrading mRNA. In this study, we show that microRNA-1 (miR-1) and microRNA-499 (miR-499) are capable of repressing the expression of the ets1 proto-oncogene, which plays a fundamental role in the extracellular matrix (ECM) degradation, a process required for tumor cell invasion and migration. We used luciferase reporter assays to demonstrate that miR-1 and miR-499 target the 3 untranslated region (UTR) of ets1. Overexpression of miR-1 and miR-499 in HepG2 cells led to downregulation of ets1 mRNA and protein as assessed by quantitative reverse transcription PCR and western blot analysis. Furthermore, overexpression of miR-1 and miR-499 inhibited the invasion and migration of HepG2 cells in matrigel invasion and transwell migration assays, respectively. These results suggest that miR-1 and miR-499 may play an important role in the pathogenesis of HCC by regulating ets1.
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Chimeric hexon HVRs protein reflects partial function of adenovirus.
Biochem. Biophys. Res. Commun.
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Adenovirus is widely used in gene therapy and vaccination as a viral vector, and its hypervariable regions (HVRs) on hexon are the main antigen recognition sites of adenovirus. The modification of this area by genetic engineering will change the antigenic specificity of the virus. In addition, recent studies have demonstrated the importance of coagulation factor X (FX) in adenovirus serotype 5-mediated liver transduction in vivo. The binding site of adenovirus to FX is the HVRs on hexon. By constructing five proteins containing chimeric HVRs from different adenovirus serotypes, we focused on the antigenic specificity and the affinity for FX of these proteins compared with the corresponding viruses. Our data showed that HVR5 and HVR7 had only a part of hexon activity to neutralizing antibodies (NAbs) compared with the complete activity of HVR1-7. Results also demonstrated a differential high-affinity interaction of the HVRs proteins with FX and indicated that HVRs protein had a similar binding ability with corresponding adenovirus serotype. These results highlighted some properties of chimeric HVRs proteins and revealed the influence on the structure and function of hexon proteins and adenovirus resulting from the HVRs.
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Filter Bank Common Spatial Pattern Algorithm on BCI Competition IV Datasets 2a and 2b.
Front Neurosci
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The Common Spatial Pattern (CSP) algorithm is an effective and popular method for classifying 2-class motor imagery electroencephalogram (EEG) data, but its effectiveness depends on the subject-specific frequency band. This paper presents the Filter Bank Common Spatial Pattern (FBCSP) algorithm to optimize the subject-specific frequency band for CSP on Datasets 2a and 2b of the Brain-Computer Interface (BCI) Competition IV. Dataset 2a comprised 4 classes of 22 channels EEG data from 9 subjects, and Dataset 2b comprised 2 classes of 3 bipolar channels EEG data from 9 subjects. Multi-class extensions to FBCSP are also presented to handle the 4-class EEG data in Dataset 2a, namely, Divide-and-Conquer (DC), Pair-Wise (PW), and One-Versus-Rest (OVR) approaches. Two feature selection algorithms are also presented to select discriminative CSP features on Dataset 2b, namely, the Mutual Information-based Best Individual Feature (MIBIF) algorithm, and the Mutual Information-based Rough Set Reduction (MIRSR) algorithm. The single-trial classification accuracies were presented using 10?×?10-fold cross-validations on the training data and session-to-session transfer on the evaluation data from both datasets. Disclosure of the test data labels after the BCI Competition IV showed that the FBCSP algorithm performed relatively the best among the other submitted algorithms and yielded a mean kappa value of 0.569 and 0.600 across all subjects in Datasets 2a and 2b respectively.
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Small-molecule inhibition of human immunodeficiency virus type 1 replication by targeting the interaction between Vif and ElonginC.
J. Virol.
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The HIV-1 viral infectivity factor (Vif) protein is essential for viral replication. Vif recruits cellular ElonginB/C-Cullin5 E3 ubiquitin ligase to target the host antiviral protein APOBEC3G (A3G) for proteasomal degradation. In the absence of Vif, A3G is packaged into budding HIV-1 virions and introduces multiple mutations in the newly synthesized minus-strand viral DNA to restrict virus replication. Thus, the A3G-Vif-E3 complex represents an attractive target for development of novel anti-HIV drugs. In this study, we identified a potent small molecular compound (VEC-5) by virtual screening and validated its anti-Vif activity through biochemical analysis. We show that VEC-5 inhibits virus replication only in A3G-positive cells. Treatment with VEC-5 increased cellular A3G levels when Vif was coexpressed and enhanced A3G incorporation into HIV-1 virions to reduce viral infectivity. Coimmunoprecipitation and computational analysis further attributed the anti-Vif activity of VEC-5 to the inhibition of Vif from direct binding to the ElonginC protein. These findings support the notion that suppressing Vif function can liberate A3G to carry out its antiviral activity and demonstrate that regulation of the Vif-ElonginC interaction is a novel target for small-molecule inhibitors of HIV-1.
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BCI Competition IV - Data Set I: Learning Discriminative Patterns for Self-Paced EEG-Based Motor Imagery Detection.
Front Neurosci
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Detecting motor imagery activities versus non-control in brain signals is the basis of self-paced brain-computer interfaces (BCIs), but also poses a considerable challenge to signal processing due to the complex and non-stationary characteristics of motor imagery as well as non-control. This paper presents a self-paced BCI based on a robust learning mechanism that extracts and selects spatio-spectral features for differentiating multiple EEG classes. It also employs a non-linear regression and post-processing technique for predicting the time-series of class labels from the spatio-spectral features. The method was validated in the BCI Competition IV on Dataset I where it produced the lowest prediction error of class labels continuously. This report also presents and discusses analysis of the method using the competition data set.
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Sphere Formation Assay is Not an Effective Method for Cancer Stem Cell Derivation and Characterization from the Caco-2 Colorectal Cell Line.
Curr Stem Cell Res Ther
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Although the existence of cancer stem cells (CSCs) has been demonstrated in colorectal cancer, further investigation is hindered by controversies over their surface markers. The sphere formation assay is widely used as in vitro method for derivation and characterization of CSCs based on the intrinsic self-renewal property of these cells. Isolated cancer cells that form tumorspheres are generally recognized as CSCs with self-renewal and tumorigenic capacities. In this study, colon spheres grown from Caco-2 cells in the sphere formation assay were separated from other differentiated cells and characterized. Compared with Caco-2 cells, the derived colon spheres lost several CSC properties. The colon spheres contained decreased levels of specific colorectal CSC surface markers as well as low levels of ATP-binding cassette (ABC) transporters typically overexpressed in CSCs, resulting in the near loss of their chemoresistance ability. Furthermore, cells that developed as colon spheres with strong self-renewal ability in vitro lost their tumorigenic capacity in vivo compared with Caco-2 cells, which could establish tumors in non-obese diabetic/severe-combined immunodeficient (NOD/SCID) mice. The results indicated that the Caco-2 cell derived colon spheres did not consist of colorectal CSCs. Thus, the well-accepted sphere formation assay may not be an effective method for CSC isolation and characterization from the Caco-2 colorectal cancer cell line.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.