bluuebunny/crossref_metadata_2025_split huggingface dataset:
GAN-based Style Transformation to Improve Gesture-recognition Accuracy
Authors: Suzuki Noeru , Watanabe Yuki , Nakazawa Atsushi 
Published: December 2020

Gesture recognition and human-activity recognition from multi-channel sensory data are important tasks in wearable and ubiquitous computing. In these tasks, increasing both the number of recognizable activity classes and the recognition accuracy is essential. However, this is usually an ill-posed problem because individual differences in the same gesture class may affect the discrimination of different gesture classes. One promising solution is to use personal classifiers, but this requires personal gesture samples for re-training the classifiers.
We propose a method of solving this issue that obtains personal gesture classifiers using few user gesture samples, thus, achieving accurate gesture recognition for an increased number of gesture classes without requiring extensive user calibration. The novelty of our method is introducing a generative adversarial network (GAN)-based style transformer to 'generate' a user's gesture data. The method synthesizes the gesture examples of the target class of a target user by transforming of a) gesture data into another class of the same user (intra-user transformation) or b) gesture data of the same class of another user (inter-user transformation). The synthesized data are then used to train the personal gesture classifier.
We conducted comprehensive experiments using 1) different classifiers including SVM and CNN, 2) intra- and inter-user transformations, 3) various data-missing patterns, and 4) two different types of sensory data. Results showed that the proposed method had an increased performance. Specially, the CNN-based classifiers increased in average accuracy from 0.747 to 0.822 in the CheekInput dataset and from 0.856 to 0.899 in the USC-HAD dataset. Moreover, the experimental results with various data-missing conditions revealed a relation between the number of missing gesture classes and the accuracy of the existing and proposed methods, and we were able to clarify several advantages of the proposed method. These results indicate the potential of considerably reducing the number of required training samples of target users.
BlinKey
Authors: Zhu Huadi , Jin Wenqiang , Xiao Mingyan , Murali Srinivasan , Li Ming 
Published: December 2020

Virtual Reality (VR) has shown promising potentials in many applications, such as e-business, healthcare, and social networking. Rich information regarding user's activities and their online accounts is stored in VR devices. If it is carelessly unattended, then attackers, including insiders, can make use of the stored information to, for example, perform in-app purchases at the legitimate owner's expenses. Current solutions, mostly following schemes designed for general personal devices, have been proved vulnerable to shoulder-surfing attacks due to the sight blocking caused by the headset. Although there have been efforts trying to fill this gap, they either rely on some highly advanced equipment, such as electrodes to read brainwaves, or introduce heavy cognitive load that has users perform a series of cumbersome authentication tasks. Therefore, an authentication method for VR devices that is robust and convenient is in dire need.
In this paper, we present the design, implementation, and evaluation of a two-factor user authentication scheme, BlinKey, for VR devices that are equipped with an eye tracker. A user's secret passcode is a set of recorded rhythms when he/she blinks, together with the unique pupil size variation pattern. We call this passcode as a blinkey, which can be jointly characterized by knowledge-based and biometric features. To examine the performances, BlinKey is implemented on an HTC Vive Pro with a Pupil Labs eye tracker. Through extensive experimental evaluations with 52 participants, we show that our scheme can achieve the average EER as low as 4.0% with only 6 training samples. Besides, it is robust against various types of attacks. BlinKey also exhibits satisfactory usability in terms of login attempts, memorability, and impact of user motions. We also carry out questionnaire-based pre-/post-studies. The survey result indicates that BlinKey is well accepted as a user authentication scheme for VR devices.
Abstract A02: SYK kinase inhibition causes autophagy pathway activation via suppression of mTORC1 in KRAS-mutant pancreatic cancer cells
Authors: Hua Kevin L. , Pan Michelle , Rafati Minoo , Singh Anurag 
Published: December 2020

Abstract
The spleen tyrosine kinase (SYK) is highly expressed in a subset of KRAS-mutant pancreatic ductal adenocarcinoma (PDAC) cell lines. This prompted our interest in investigating SYK as a candidate therapeutic target in PDAC cell lines. Here, we use a selective SYK kinase inhibitor (PRT-062607) in pharmacologic and mechanistic studies of SYK kinase signaling in PDAC cell lines. SYK kinase inhibition causes dose-dependent decreases in cell proliferation of “SYK-high” PDAC cell lines YAPC and DAN-G. Furthermore, combined SYK and MEK inhibition causes additive effects on reducing cell proliferation. Mechanistically, SYK inhibition causes reduced S6K and rpS6 phosphorylation, which is independent of MEK/ERK and PI3K/AKT signaling. Therefore, SYK activates mTORC1 activity through an unknown mechanism. The mTORC1 complex is a key activator of the macroautophagy pathway (autophagy), which is implicated as a driver of PDAC progression. However, autophagy can cause tumor suppression in some contexts. We demonstrate that SYK inhibition or shRNA-mediated depletion results in increased autolysosomal biogenesis and autophagic flux that occur with latency following treatment of cells with the SYK inhibitor. These effects are partly mediated by the nuclear localization and activation of MITF, which is a key transcriptional regulator of genes that control lysosomal biogenesis and autophagy. Taken together, our results demonstrate that SYK is a positive regulator of mTORC1 activity in a subset of PDAC cell lines. SYK kinase inhibition or shRNA-mediated depletion causes a strong reduction in mTORC1 activity and subsequent MITF activation and nuclear localization. The net effect is increased autolysosomal biogenesis and autophagic flux in YAPC and DAN-G PDAC cell lines. Therefore, SYK inhibition in combination with KRAS pathway inhibitors may serve as a potential therapeutic strategy to perturb autophagy pathway homeostasis and pancreatic cancer cell survival.
Citation Format: Kevin L. Hua, Michelle Pan, Minoo Rafati, Anurag Singh. SYK kinase inhibition causes autophagy pathway activation via suppression of mTORC1 in KRAS-mutant pancreatic cancer cells [abstract]. In: Proceedings of the AACR Special Conference on Targeting PI3K/mTOR Signaling; 2018 Nov 30-Dec 8; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(10_Suppl):Abstract nr A02.
Abstract A09: Phosphorylation of mSin1-CRIM domain regulates protein stability and substrate selectivity
Authors: Chiu Yueh-Ho , Cui Wei 
Published: December 2020

Abstract
The mechanistic target of rapamycin (mTOR) signaling plays critical roles in controlling mammalian cell behavior and function in response to environmental changes, and thereby it is important for maintaining tissue homeostasis and organism health. Dysregulation of mTOR signaling leads to a variety of human diseases, such as cancer, obesity, type II diabetes, and neurodegeneration. The mTOR signaling functions through two distinct multiprotein complexes known as mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2), which differ in their composition, structures, and functions. Considerable knowledge has been obtained regarding mTORC1 in recent years, while, in comparison, much less is known about mTORC2. Rictor and mSin1 are key mTORC2-specific proteins and essential for mTORC2 functions. Rictor is a scaffold protein in mTORC2 as Raptor in mTORC1, while mSin1 is considered to function for recruiting the substrate to the mTORC2 and its expression appears to be Rictor-dependent. However, exact mechanisms remain elusive. To explore the relationship between Rictor and mSin1 and their functions in mTORC2, we have generated RICTOR-knockout HEK293T cells by using the CRISPR-Cas9 system and revealed that mSin1 protein expression was substantially diminished in these cells and so was the mTORC2 activity, whereas mSin1 mRNA expression did not show any changes in the absence of RICTOR. Further analyses demonstrated that Rictor/mTORC2 is crucial for mSin1 protein stability, which may be attributed, at least partly, to the mTORC2-associated phosphorylation of mSin1-CRIM domain. More interestingly, this phosphorylation may also affect substrate recognition of mTORC2. The detailed mechanistic study regarding the influence of phosphorylated mSin1 on mTORC2 activity has been carried out and will be presented at the meeting. Our results suggest that mTORC2 may have an autoregulatory function and affect its substrate selection. Our findings thus advance our understanding in both regulation and function of Rictor/mTORC2, and also provide a potential insight for new therapies development in a number of human diseases.
Citation Format: Yueh-Ho Chiu, Wei Cui. Phosphorylation of mSin1-CRIM domain regulates protein stability and substrate selectivity [abstract]. In: Proceedings of the AACR Special Conference on Targeting PI3K/mTOR Signaling; 2018 Nov 30-Dec 8; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(10_Suppl):Abstract nr A09.
Abstract A13: Mammalian EAK-7 activates alternative mTOR signaling to regulate cell proliferation and migration
Authors: Nguyen Joe T. , Ray Connor , Fox Alexandra L , Mendonca Daniela B , Kim Jin Koo , Krebsbach Paul H. 
Published: December 2020

Abstract
Nematode EAK-7 (enhancer-of-akt-1-7) regulates dauer formation and controls life span; however, the function of the human ortholog mammalian EAK-7 (mEAK-7) is unknown. We report that mEAK-7 activates an alternative mechanistic/mammalian target of rapamycin (mTOR) signaling pathway in human cells, in which mEAK-7 interacts with mTOR at the lysosome to facilitate S6K2 activation and 4E-BP1 repression. Despite interacting with mTOR and mammalian lethal with SEC13 protein 8 (mLST8), mEAK-7 does not interact with other mTOR complex 1 (mTORC1) or mTOR complex 2 (mTORC2) components; however, it is essential for mTOR signaling at the lysosome. This phenomenon is distinguished by S6 and 4E-BP1 activity in response to nutrient stimulation. Conventional S6K1 phosphorylation is uncoupled from S6 phosphorylation in response to mEAK-7 knockdown. mEAK-7 recruits mTOR to the lysosome, a crucial compartment for mTOR activation. Loss of mEAK-7 results in a marked decrease in lysosomal localization of mTOR, whereas overexpression of mEAK-7 results in enhanced lysosomal localization of mTOR. Deletion of the carboxyl terminus of mEAK-7 significantly decreases mTOR interaction. mEAK-7 knockdown decreases cell proliferation and migration, whereas overexpression of mEAK-7 enhances these cellular effects. Constitutively activated S6K rescues mTOR signaling in mEAK-7–knocked down cells. Thus, mEAK-7 activates an alternative mTOR signaling pathway through S6K2 and 4E-BP1 to regulate cell proliferation and migration.
Citation Format: Joe T. Nguyen, Connor Ray, Alexandra L Fox, Daniela B Mendonca, Jin Koo Kim, Paul H. Krebsbach. Mammalian EAK-7 activates alternative mTOR signaling to regulate cell proliferation and migration [abstract]. In: Proceedings of the AACR Special Conference on Targeting PI3K/mTOR Signaling; 2018 Nov 30-Dec 8; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(10_Suppl):Abstract nr A13.
Abstract A17: Targeting PI3K/Akt-mediated MADD phosphorylation improves TRAIL sensitivity in anaplastic thyroid cancer
Authors: Saini Shikha , Mathur Aditi , Yue Fei , Maker Ajay , Prabhakar Bellur S. 
Published: December 2020

Abstract
Anaplastic thyroid cancer is an extremely hard-to-treat malignancy due to its aggressiveness, metastasis and inherent therapeutic resistance. Despite using all available armamentaria, the median survival of ATC patients remains dismal. In this regard, TNF-related apoptosis-inducing ligand (TRAIL) is known to induce cancer-specific apoptosis without affecting nontumor cells. However, development of resistance to TRAIL hampers its clinical use. One of the mechanisms of TRAIL resistance is mediated through phosphorylation of Map kinase Activating Death Domain-containing protein (MADD) by Akt. In light of this, preventing MADD phosphorylation might be a rational approach to overcome TRAIL resistance. To test this, we examined MADD expression and TRAIL sensitivity by Western blotting and active caspase-3 staining in several ATC cell lines harboring mutations in cancer driver genes including BRAF, Akt, and PTEN. MADD phosphorylation was inhibited by introducing site-directed mutations in Akt phosphorylation sites of MADD and exogenously expressing the mutant constructs to determine the effect on TRAIL-induced apoptosis. Our results showed that MADD was differentially overexpressed in all ATC cells compared to the normal thyroid tissues irrespective of their mutational landscape. Further, exogenous expression of non-phosphorylatable MADD resulted in a significantly increased TRAIL-induced apoptosis accompanied by the activation of both intrinsic and extrinsic apoptotic pathways. Thus, this study establishes a concept of prevention of MADD phosphorylation to improve TRAIL susceptibility of ATC cells as it can yield similar results as that of blocking PI3k/Akt pathway without any off-target effects. Further studies are warranted to explore specific inhibitors to target MADD phosphorylation.
Note: This abstract was not presented at the conference.
Citation Format: Shikha Saini, Aditi Mathur, Fei Yue, Ajay Maker, Bellur S. Prabhakar. Targeting PI3K/Akt-mediated MADD phosphorylation improves TRAIL sensitivity in anaplastic thyroid cancer [abstract]. In: Proceedings of the AACR Special Conference on Targeting PI3K/mTOR Signaling; 2018 Nov 30-Dec 8; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(10_Suppl):Abstract nr A17.
Abstract A30: Targeting of the mTOR pathway in human acute myeloid leukemia cells using functionalized gold nanoparticles
Authors: Yasinska Inna M. , Gibbs Bernhard F. , Varani Luca , Hussain Rohanah , Siligardi Giuliano , Fasler-Kan Elizaveta , Calzolai Luigi , Sumbayev Vadim V. 
Published: December 2020

Abstract
Specific targeting of fundamental biochemical/signaling pathways in human malignant cells with the purpose of recognition and delivery of cytotoxic drugs into them is a very promising but not well-developed strategic approach. It is a major focus of current molecular cancer research, nanomedicine, biotechnology, and synthetic biology. mTOR pathway is a master regulator of metabolism and cell growth in the majority of malignant cells. Especially this applies to cancerous myeloid cells where it determines the ability of the cells to survive and evade the host immune surveillance. Therefore, specific targeting of this pathway could be a novel strategy for treatment of acute myeloid leukemia (AML), a blood/bone marrow cancer that can rapidly progress into a systemic and often fatal malignancy. In this study we demonstrated for the first time a fundamentally novel approach for specific targeting of human AML cells by functionalized gold nanoparticles. The immune receptor Tim-3 is highly expressed in human AML cells. It is one of the key members of the Tim-3/galectin-9 autocrine pathway that plays a pivotal role in AML cell survival and immune evasion (1). Rapamycin inhibits the mTOR activity, thus affecting translational pathways in AML cells. Inhibition of the mTOR leads to a rapid killing of AML cells. Using these nanomaterials, we managed to successfully deliver rapamycin into AML cells, reaching attenuation of the mTOR activity. Concentration of rapamycin required to reach such a strong effect was at least 50 times lower compared to that of free rapamycin required to achieve the similar result. We therefore concluded that our technology is of potential use for specific targeting of AML cells for the purpose of diagnosis and possibly therapy (2). The nanoconjugates developed in our work can be used to specifically identify malignant blood cells, thus allowing rapid and robust AML diagnosis.
Citation Format: Inna M. Yasinska, Bernhard F. Gibbs, Luca Varani, Rohanah Hussain, Giuliano Siligardi, Elizaveta Fasler-Kan, Luigi Calzolai, Vadim V. Sumbayev. Targeting of the mTOR pathway in human acute myeloid leukemia cells using functionalized gold nanoparticles [abstract]. In: Proceedings of the AACR Special Conference on Targeting PI3K/mTOR Signaling; 2018 Nov 30-Dec 8; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(10_Suppl):Abstract nr A30.
Abstract B01: Simultaneous targeting of mTOR and mLST8 in human breast cancer cells
Authors: Coyle Melissa , Nabiee Romina , Lamboy Robert , Mahdipoor Parvin , Parang Keykavous , Aliabadi Hamidreza Montazeri 
Published: December 2020

Abstract
Despite our continually increasing knowledge of cancer biology and intracellular mechanisms, identifying targets for cancer treatment remains a challenge. Cancer cells are heterogeneous and plastic, which are involved in innate and acquired resistance to molecularly targeted anticancer drugs, respectively. This project focuses on the PI3K/Akt cell signaling pathway, specifically mammalian target of rapamycin (mTOR) and GβL (mLST8), to halt cell proliferation. The breast cancer cell lines MDA-MB-231, MDA-MB-468, and AU565 were exposed to small interfering RNAs (siRNAs) targeting mTOR or mLST8, as well as a combination of both. The cell protein expression profile was studied to investigate the efficiency of protein silencing, and potential synergistic effect on downstream effectors of the pathway. Due to poor cellular internalization of siRNA, we also investigated the efficiency of small cell-penetrating peptides specifically designed as siRNA carriers. Three cyclic peptides (WR5, [R5K]W5 and [R6K]W6) incorporating ring-forming arginines (as a cationic moiety for inter-ionic interaction with nucleic acids), tryptophan (as a hydrophobic chain to enhance interaction with cell membrane, and lysine as the conjugation site for tryptophan chain were studied for in vitro siRNA delivery. The siRNA complexes formed with these amphiphilic peptides were delivered to the same breast cancer cell lines, and the efficiency of cellular internalization and mTOR and mLST8 silencing was investigated. Our findings confirm the efficiency of siRNAs in interrupting formation of mTOR complexes, and the activation of downstream proteins. Further studies are required to confirm these findings in patient cells and to evaluate the efficacy of this approach in vivo.
Citation Format: Melissa Coyle, Romina Nabiee, Robert Lamboy, Parvin Mahdipoor, Keykavous Parang, Hamidreza Montazeri Aliabadi. Simultaneous targeting of mTOR and mLST8 in human breast cancer cells [abstract]. In: Proceedings of the AACR Special Conference on Targeting PI3K/mTOR Signaling; 2018 Nov 30-Dec 8; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(10_Suppl):Abstract nr B01.
Abstract B02: Combined inhibition of mTOR and Src family kinases enhances treatment effects in prostate cancer cells
Authors: Dai Yao , Siemann Dietmar W 
Published: December 2020

Abstract
Hyperactivated Akt/mTOR pathway and Src family kinases (SFKs) pathway commonly occur in prostate cancer that is highly associated with disease progression and poor prognosis. Therefore, small-molecule inhibitors targeting these pathways have been studied extensively for the treatment of advanced prostate cancer. Nevertheless, clinical observation suggests that individual treatment with either inhibitor only yields limited antitumor effects in patients. One possible interpretation is that these signaling pathways are redundant, such that blocking one pathway is not sufficient to yield considerable efficacies. In this regard, we combined mTOR inhibitor rapamycin and Src inhibitor dasatinib to detect functional behaviors in prostate cancer cells. Cell proliferation was detected by MTT, and clonogenic survival was tested by colony formation assay. Cell migration was assessed by “wound-healing” scratch assay. Protein expression was detected by Western blot analysis. We found that rapamycin plus dasatinib showed greater inhibition on cell proliferation and clonogenic survival than either single agent. Such combination effects were additive in PC-3 and synergistic in DU145 cells, respectively, as reflected by combination index calculation. In addition, cell migration was suppressed to a greater extent by combination treatment than either treatment alone. At the molecular level, co-targeting mTOR and SFKs leads to strong inhibition of not only phosphorylation of these two proteins but also their downstream components such as Akt, focal adhesion kinase (FAK), S6K and 4E-BP1. These data indicate that co-targeting mTOR and Src pathways is able to achieve enhanced tumor-suppressing effects in prostate cancer cells with overexpression of both kinases, suggesting that this combinative intervention modality may serve as a potential anticancer strategy that could be further tested in advanced prostate cancer models in vivo.
Note: This abstract was not presented at the conference.
Citation Format: Yao Dai, Dietmar W Siemann. Combined inhibition of mTOR and Src family kinases enhances treatment effects in prostate cancer cells [abstract]. In: Proceedings of the AACR Special Conference on Targeting PI3K/mTOR Signaling; 2018 Nov 30-Dec 8; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(10_Suppl):Abstract nr B02.
Abstract B28: Estrogen receptor alpha (ERa) promotes protein synthesis by fine-tuning the expression of the eukaryotic translation initiation factor 3 subunit f (eIF3f)
Authors: Cuesta Rafael , Holz Marina K. 
Published: December 2020

Abstract
Approximately two-thirds of all breast cancer cases are estrogen receptor (ER) positive. The treatment of this breast cancer subtype with endocrine therapies is effective in the adjuvant and recurrent settings. However, their effectiveness is compromised by the emergence of intrinsic or acquired resistance. Thus, identification of new molecular targets can significantly contribute to the development of novel therapeutic strategies. In recent years, many studies have implicated aberrant levels of translation initiation factors in cancer etiology and provided evidence that identifies these factors as promising therapeutic targets. Accordingly, we observed reduced levels of the eukaryotic translation initiation factor 3 (eIF3) subunit eIF3f in ER-positive breast cancer cells compared to ER-negative cells and determined that low eIF3f levels are required for proper proliferation and survival of ER-positive MCF7 cells. The expression of eIF3f is tightly controlled by ERa at transcriptional (genomic pathway) and translational (non-genomic pathway) level. Specifically, estrogen-bound ERa represses transcription of the EIF3F gene, while promoting eIF3f mRNA translation. In regulation of translation, estrogen activates the mTORC1 pathway, which enhances the binding of eIF3 to the eIF4F complex and, consequently, the assembly of 48S preinitiation complexes and protein synthesis. We observed preferential translation of mRNAs with highly structured 5' untranslated regions (UTRs) that usually encode factors involved in cell proliferation and survival (e.g., cyclin D1 and survivin). Our results underscore the importance of estrogen-ERa-mediated control of eIF3f expression for the proliferation and survival of ER-positive breast cancer cells. These findings may provide rationale for the development of new therapies to treat ER-positive breast cancer.
Citation Format: Rafael Cuesta, Marina K. Holz. Estrogen receptor alpha (ERa) promotes protein synthesis by fine-tuning the expression of the eukaryotic translation initiation factor 3 subunit f (eIF3f) [abstract]. In: Proceedings of the AACR Special Conference on Targeting PI3K/mTOR Signaling; 2018 Nov 30-Dec 8; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(10_Suppl):Abstract nr B28.