75 research outputs found

    Bivariate Beta-LSTM

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    Long Short-Term Memory (LSTM) infers the long term dependency through a cell state maintained by the input and the forget gate structures, which models a gate output as a value in [0,1] through a sigmoid function. However, due to the graduality of the sigmoid function, the sigmoid gate is not flexible in representing multi-modality or skewness. Besides, the previous models lack modeling on the correlation between the gates, which would be a new method to adopt inductive bias for a relationship between previous and current input. This paper proposes a new gate structure with the bivariate Beta distribution. The proposed gate structure enables probabilistic modeling on the gates within the LSTM cell so that the modelers can customize the cell state flow with priors and distributions. Moreover, we theoretically show the higher upper bound of the gradient compared to the sigmoid function, and we empirically observed that the bivariate Beta distribution gate structure provides higher gradient values in training. We demonstrate the effectiveness of bivariate Beta gate structure on the sentence classification, image classification, polyphonic music modeling, and image caption generation.Comment: AAAI 202

    Counterfactual Fairness with Disentangled Causal Effect Variational Autoencoder

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    The problem of fair classification can be mollified if we develop a method to remove the embedded sensitive information from the classification features. This line of separating the sensitive information is developed through the causal inference, and the causal inference enables the counterfactual generations to contrast the what-if case of the opposite sensitive attribute. Along with this separation with the causality, a frequent assumption in the deep latent causal model defines a single latent variable to absorb the entire exogenous uncertainty of the causal graph. However, we claim that such structure cannot distinguish the 1) information caused by the intervention (i.e., sensitive variable) and 2) information correlated with the intervention from the data. Therefore, this paper proposes Disentangled Causal Effect Variational Autoencoder (DCEVAE) to resolve this limitation by disentangling the exogenous uncertainty into two latent variables: either 1) independent to interventions or 2) correlated to interventions without causality. Particularly, our disentangling approach preserves the latent variable correlated to interventions in generating counterfactual examples. We show that our method estimates the total effect and the counterfactual effect without a complete causal graph. By adding a fairness regularization, DCEVAE generates a counterfactual fair dataset while losing less original information. Also, DCEVAE generates natural counterfactual images by only flipping sensitive information. Additionally, we theoretically show the differences in the covariance structures of DCEVAE and prior works from the perspective of the latent disentanglement

    Production of CMAH Knockout Preimplantation Embryos Derived From Immortalized Porcine Cells Via TALE Nucleases

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    Although noncancerous immortalized cell lines have been developed by introducing genes into human and murine somatic cells, such cell lines have not been available in large domesticated animals like pigs. For immortalizing porcine cells, primary porcine fetal fibroblasts were isolated and cultured using the human telomerase reverse transcriptase (hTERT) gene. After selecting cells with neomycin for 2 weeks, outgrowing colonized cells were picked up and subcultured for expansion. Immortalized cells were cultured for more than 9 months without changing their doubling time (similar to 24 hours) or their diameter (< 20 mu m) while control cells became replicatively senescent during the same period. Even a single cell expanded to confluence in 100 mm dishes. Furthermore, to knockout the CMAH gene, designed plasmids encoding a transcription activator-like effector nuclease (TALENs) pairs were transfected into the immortalized cells. Each single colony was analyzed by the mutation-sensitive T7 endonuclease I assay, fluorescent PCR, and dideoxy sequencing to obtain three independent clonal populations of cells that contained biallelic modifications. One CMAH knockout clone was chosen and used for somatic cell nuclear transfer. Cloned embryos developed to the blastocyst stage. In conclusion, we demonstrated that immortalized porcine fibroblasts were successfully established using the human hTERT gene, and the TALENs enabled biallelic gene disruptions in these immortalized cells.

    Increased accuracy of estrus prediction using ruminoreticular biocapsule sensors in Hanwoo (Bos taurus coreanae) cows

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    Visual estrus observation can only be confirmed at a rate of 50%–60%, which is lower than that obtained using a biosensor. Thus, the use of biosensors provides more opportunities for artificial insemination because it is easier to confirm estrus than by visual observation. This study determines the accuracy of estrus prediction using a ruminoreticular biosensor by analyzing ruminoreticular temperature during the estrus cycle and measuring changes in body activity. One hundred and twenty-five Hanwoo cows (64 with a ruminal biosensor in the test group and 61 without biosensors in the control group) were studied. Ruminoreticular temperatures and body activities were measured every 10 min. The first service of artificial insemination used gonadotropin-releasing hormone (GnRH)-based fixed-time artificial insemination protocol in the control and test groups. The test group received artificial insemination based on the estrus prediction made by the biosensor, and the control group received artificial insemination according to visual estrus observation. Before artificial insemination, the ruminoreticular temperature was maintained at an average of 38.95 ± 0.05°C for 13 h (−21 to −9 h), 0.73°C higher than the average temperature observed at −48 h (38.22 ± 0.06°C). The body activity, measured using an indwelling 3-axis accelerometer, averaged 1502.57 ± 27.35 for approximately 21 h from −4 to −24 h before artificial insemination, showing 203 indexes higher body activity than −48 hours (1299 ± 9.72). Therefore, using an information and communication techonology (ICT)-based biosensor is highly effective because it can reduce the reproductive cost of a farm by accurately detecting estrus and increasing the rate of estrus confirmation in cattle

    DsRed gene expression by doxycycline in porcine fibroblasts and cloned embryos using transposon

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    To develop a transgenic pig, introduction of foreign genes into fibroblasts is required. In this study, Piggybac transposition was used to produce tetracycline dependent gene expressing cloned embryos. Red fluorescence proteins (DsRed) combined with tetracycline promoter flanked transposon sequences were transfected into fetal fibroblasts, and the transfected cells were used as the donor for somatic cell nuclear transfer. Induction of DsRed expression was successfully controlled by doxycycline treatment in donor fibroblasts and early stage embryos. In conclusion, this study suggested that Piggybac transposition could deliver genes into cells or embryos for developing transgenic pig.Keywords: Miniature pigs, transfection, Piggybac, somatic cell nuclear transfer (SCNT), RFPAfrican Journal of Biotechnology Vol. 12(21), pp. 3188-319

    Identification of TUBB2A by quantitative proteomic analysis as a novel biomarker for the prediction of distant metastatic breast cancer

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    Background Metastasis of breast cancer to distal organs is fatal. However, few studies have identified biomarkers that are associated with distant metastatic breast cancer. Furthermore, the inability of current biomarkers, such as HER2, ER, and PR, to differentiate between distant and nondistant metastatic breast cancers accurately has necessitated the development of novel biomarker candidates. Methods An integrated proteomics approach that combined filter-aided sample preparation, tandem mass tag labeling (TMT), high pH fractionation, and high-resolution MS was applied to acquire in-depth proteomic data from FFPE distant metastatic breast cancer tissues. A bioinformatics analysis was performed with regard to gene ontology and signaling pathways using differentially expressed proteins (DEPs) to examine the molecular characteristics of distant metastatic breast cancer. In addition, real-time polymerase chain reaction (RT-PCR) and invasion/migration assays were performed to validate the differential regulation and function of our protein targets. Results A total of 9441 and 8746 proteins were identified from the pooled and individual sample sets, respectively. Based on our criteria, TUBB2A was selected as a novel biomarker candidate. The metastatic activities of TUBB2A were subsequently validated. In our bioinformatics analysis using DEPs, we characterized the overall molecular features of distant metastasis and measured differences in the molecular functions of distant metastatic breast cancer between breast cancer subtypes. Conclusions Our report is the first study to examine the distant metastatic breast cancer proteome using FFPE tissues. The depth of our dataset allowed us to discover a novel biomarker candidate and a proteomic characteristics of distant metastatic breast cancer. Distinct molecular features of various breast cancer subtypes were also established. Our proteomic data constitute a valuable resource for research on distant metastatic breast cancer.This work was supported by the Industrial Strategic Technology Development Program (#10079271 and #20000134), funded by the Ministry of Trade, Industry, and Energy (MOTIE, Korea); the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant Number: HI17C0048); the Basic Science Research Program through the Seoul National University Hospital Research Fund (26-2016-0020); and the National Research Foundation of Korea (NRF), funded by the Ministry of Science, ICT & Future Planning (Grant Number: 2018R1A1A1A05077484)

    Oncologic outcomes after immediate breast reconstruction following mastectomy: comparison of implant and flap using propensity score matching

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    Although immediate breast reconstruction has been reported to be oncologically safe, no affirmative study comparing the two reconstruction methods exists. We investigated breast cancer recurrence rates in two breast reconstruction types; implant reconstruction and autologous flap reconstruction. A retrospective cohort study was performed on propensity score-matched (for age, stage, estrogen receptor status) patients who underwent IBR after mastectomy at Seoul National University Hospital between 2010 and 2014. The main outcomes determined were locoregional recurrence-free interval (LRRFI) and disease-free interval (DFI). We analyzed 496 patients among 731 patients following propensity score matching (Median age 43, 247 implant reconstruction and 249 flap reconstruction). During median follow-up of 58.2 months, DFI was not different between the two groups at each tumor stage. However, flap reconstruction showed inferior DFI compared to implant reconstruction in patients with high histologic grade (p = 0.012), and with high Ki-67 (p = 0.028). Flap reconstruction was related to short DFI in multivariate analysis in aggressive tumor subsets. Short DFI after flap reconstruction in aggressive tumor cell phenotype was most evident in hormone positive/Her-2 negative cancer (p = 0.008). LRRFI, on the other hand, did not show difference according to reconstruction method regardless of tumor cell aggressiveness. Although there is no difference in cancer recurrence according to reconstruction method in general, flap-based reconstruction showed higher systemic recurrence associated with histologically aggressive tumors
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