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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment for both malignant and nonmalignant hematologic disorders. However, graft-versus-host disease (GVHD) and malignant relapse limit its therapeutic success. We previously demonstrated that the blockade of interferon-gamma receptor (IFNGR) signaling in donor T cells resulted in a reduction in GVHD while preserving graft-versus-leukemia (GVL) effects. However, the underlying molecular mechanisms remain inconclusive. In this study, we found that S100A9 is a novel GVHD suppressor upregulated when IFNGR is blocked in T cells. Both Ifngr1−/− and S100a9-overexpressing T cells significantly reduced GVHD without compromising GVL, altering donor T-cell trafficking to GVHD target organs in our mouse model of allo-HSCT. In addition, in vivo administration of recombinant murine S100A9 proteins prolongs the overall survival of recipient mice. Furthermore, in vivo administration of anti-human IFNGRα neutralizing antibody (αhGR-Nab) significantly upregulates the expression of S100A9 in human T cells and improved GVHD in our mouse model of xenogeneic human peripheral blood mononuclear cell transplantation. Consistent with S100a9-overexpressing T cells in our allo-HSCT model, αhGR-Nab reduced human T-cell trafficking to the GVHD target organs. Taken together, S100A9, a downstream molecule suppressed by IFNGR signaling, functions as a novel GVHD suppressor without compromising GVL.

Despite the curative potential of hematopoietic stem cell transplantation (HSCT), conditioning-associated toxicities preclude broader clinical application. Antibody-drug conjugates (ADCs) provide an attractive approach to HSCT conditioning that minimizes toxicity while retaining efficacy. Initial studies of ADC conditioning have largely focused on syngeneic HSCT. However, to treat acute leukemias or induce tolerance for solid organ transplantation, this approach must be expanded to allogeneic HSCT (allo-HSCT). Using murine allo-HSCT models, we show that pharmacologic Janus kinase 1/2 (JAK1/2) inhibition combined with CD45- or cKit-targeted ADCs enables robust multilineage alloengraftment. Strikingly, myeloid lineage donor chimerism exceeding 99% was achievable in fully MHC-mismatched HSCT using this approach. Mechanistic studies using the JAK1/2 inhibitor baricitinib revealed marked impairment of T and NK cell survival, proliferation, and effector function. NK cells were exquisitely sensitive to JAK1/2 inhibition due to interference with IL-15 signaling. Unlike irradiated mice, ADC-conditioned mice did not develop pathogenic graft-versus-host alloreactivity when challenged with mismatched T cells. Finally, the combination of ADCs and baricitinib balanced graft-versus-host disease and graft-versus-leukemia responses in delayed donor lymphocyte infusion models. Our allo-HSCT conditioning strategy exemplifies the promise of immunotherapy to improve the safety of HSCT for treating hematologic diseases.

이 연구의 목적은 포르투갈어 말하기 능력을 향상시키기 위한 방안으로 게이미피케이션 개념을 접목하여 신규 개발된 외국어로서의 포르투갈어 교재 Conversando em Portugues (Talking in Portuguese) (2019)의 교수·학습법에 대해 소개하고자 한다. 이를 통해, 게이미피케이션 외국어 교수·학습 전략 수립에 필요한 구성 요소들과 방법론을 비롯해, 청중응답시스템(ARS) 기반 설계 표본을 제시하고자 한다. 게이미피케이션은 이미 초등 교육부터 대학 교육에 이르기까지 외국어 교수·학습법에 널리 적용되고 있다. 특히 학습 동기 유발과 학습자들 간의 긴밀한 상호작용이 중요시되는 말하기 교육에 있어 게이미피케이션은 효과적인 교수·학습 전략이 될 수 있다. 이를 위해 본 연구에서는 자기결정이론(SDT)을 이론적 틀로 활용하여 학습 동기 부여와 학습자의 몰입도 제고를 위한 외국어 학습용 게임을 설계하였다.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the main therapeutic strategy for patients with both malignant and nonmalignant disorders. The therapeutic benefits of allo-HSCT in malignant disorders are primarily derived from the graft-versus-leukemia (GvL) effect, in which T cells in the donor graft recognize and eradicate residual malignant cells. However, the same donor T cells can also recognize normal host tissues as foreign, leading to the development of graft-versus-host disease (GvHD), which is difficult to separate from GvL and is the most frequent and serious complication following allo-HSCT. Inhibition of donor T cell toxicity helps in reducing GvHD but also restricts GvL activity. Therefore, developing a novel therapeutic strategy that selectively suppresses GvHD without affecting GvL is essential. Recent studies have shown that inhibition of histone deacetylases (HDACs) not only inhibits the growth of tumor cells but also regulates the cytotoxic activity of T cells. Here, we compile the known therapeutic potential of HDAC inhibitors in preventing several stages of GvHD pathogenesis. Furthermore, we will also review the current clinical features of HDAC inhibitors in preventing and treating GvHD as well as maintaining GvL.

Kaposi's sarcoma-associated herpesvirus (KSHV) is associated with formation of Kaposi's sarcoma, multicentric Castleman's disease, and primary effusion lymphoma. Replication and transcription activator (RTA) genes are expressed upon reactivation of KSHV, which displays a biphasic life cycle consisting of latent and lytic replication phases. RTA protein expression results in KSHV genome amplification and successive viral lytic gene expression. Transcriptional activity of viral lytic genes is regulated through epigenetic modifications. In Raji cells latently infected with Epstein-Barr virus, various modifications, such as acetylation and methylation, have been identified at specific lysine residues in histone H4 during viral reactivation, supporting the theory that expression of specific lytic genes is controlled by histone modification processes. Data obtained from chromatin immunoprecipitation and quantitative real-time PCR analyses revealed alterations in the H4K8ac and H4K20me3 levels at lytic gene promoters during reactivation. Our results indicate that H4K20me3 is associated with the maintenance of latency, while H4K8ac contributes to KSHV reactivation in infected TREx BCBL-1 RTA cells.

We present a plasmonic-based strategy for the colourimetric and spectroscopic differentiation of various organic acids produced by bacteria. The strategy is based on our discovery that particular concentrations of dl-lactic, acetic, and butyric acids induce different assembly structures, colours, and optical spectra of gold nanoparticles. We selected wild-type (K-12 W3110) and genetically-engineered (JHL61) Escherichia coli (E. coli) that are known to primarily produce acetic and butyric acid, respectively. Different assembly structures and optical properties of gold nanoparticles were observed when different organic acids, obtained after the removal of acid-producing bacteria, were mixed with gold nanoparticles. Moreover, at moderate cell concentrations of K-12 W3110 E. coli, which produce sufficient amounts of acetic acid to induce the assembly of gold nanoparticles, a direct estimate of the number of bacteria was possible based on time-course colour change observations of gold nanoparticle aqueous suspensions. The plasmonic-based colourimetric and spectroscopic methods described here may enable onsite testing for the identification of organic acids produced by bacteria and the estimation of bacterial numbers, which have applications in health and environmental sciences.

As potential oral and topical drug delivery applications, we fabricate oil–drug@molecularly-oriented hydrogel shells particles with regulated molecular orientation, for improved loading efficiencies, controlled and pH-specific releases, and anti-denaturation of hydrophilic drugs. The hydrogel shell is made with a natural polymer (alginate or curdlan) and Ca 2+ , and features oriented/crystallized structures. With a simple drop-dripping device, an optimum condition is established to encapsulate an oil–hydrophilic drug mixture with these shells and to manipulate molecular orientation/crystal structures of hydrogel shells. As a result, drug (arbutin) loading efficiencies are increased to 90% in the particles. In addition, depending on the types of physicochemical properties of hydrogel shells, not only pH-selective (in simulated gastric or intestinal fluid) but also pH-insensitive drug releases of oil–drug@hydrogel particles are possible. Moreover, due to crystals' excellent barrier properties, highly oriented hydrogels are also effective in preventing the denaturation of l -ascorbic acid, enabling long-lasting therapeutic effects of drug. This particulate system can also load a variety of functional materials in oil core of the core-shell particles and hence could expand the application to various fields.

Digital paradigms became the lens from where we view the world. Now all of us pay attention to how does the digital paradigms shift affect the world around us. In turn, the ongoing introduction of new technologies and the increasing importance of computational thinking continue to reframe the debate on instructional practice, improvement and student learning in education. Literature instructors are also today being forced to think about 'how to teach', rather than 'what to teach'. Aware of the issues, this paper proposes a new instructional model using big data suitable to be used to teach literary history. Today's learners are different. They had grown up surrounded with an excess of technology and media use in everyday life. This paper provides them with opportunities to make literary studies more attractive and easier to understand. Through this, it attempts to explore theoretically educational methodology of studying literary history in order to encourage learners' meaningful participation in classroom.

We present gold (Au) and silver (Ag) nanoparticles (NPs) could be used not only for stimuli-responsive optical sensors but also for the quantification of radical compounds when these nanoparticles are suitably combined with polymeric materials. When Au NPs are assembled 2-dimensionally on the surface of hydrogel NPs which respond to temperatures, the hybrid NPs displayed thermoreversible multiple color switching. Accordingly, optical bandwidths of the hybrid NPs are reversibly changed with temperatures: with hybrid NPs assembled with 51 nm Au NPs, prominent optical signals are recorded at 900 nm at 50 °C while most of extinction signals are shown below 600 nm at room temperatures. In addition, we demonstrate the modification of Ag NPs’ surfaces (nanocubes and nanospheres) with polyelectrolytes (either positive or negative) could extend the quantifiable detection ranges of radical compounds. Through the surface modification of Ag NPs, the polyelectrolytes protect the Ag NPs by probably either retarding (forming diffusion barriers) or preventing (blocking/entrapping/scavenging) the arrival of radicals to Ag NPs or both. The roles of the polyelectrolytes are demonstrated by using radical compounds produced from tetrahydrofuran and H2O2. From the results, we could obtain calibration curves for the wide-range quantification of radical compounds.

Although a lot of research is being conducted to apply augmented reality (AR) to education, there is little adequate research on how to design AR-based learning systems so that they foster deep understanding in learners. In this article, we present and exemplify a learnercentered instructional model that incorporates AR contents as a form of blended learning strategy. To this end, we divide the instructional model into lecture-type formal learning and purely self-directed form of informal learning, and go on to explain the methodology and process of designing instructional model according to each type. Through this approach, we show that the benefits of using AR extend into the realm of education, and verify that ARbased learning systems offer a potentially effective method for foreign language instruction.

The purpose of this study was to investigate on parenting stress, parenting guilt feelings and separation anxiety and alternative care in nurses. Data were collected from nurses with preschooler at 2 hospitals from August 2013 to January 2014. Self reported questionnaires were used to collect data from 163 nurses. There were significant differences according to the age, satisfaction of work place and co-worker, spouse support of parenting in parenting stress, parenting guilt feelings and separation anxiety in common. The majority type of alternative care was surrogate foster home when they went to work. However, there were significant differences according to type of alternative care in parenting stress, parenting guilt feelings and separation anxiety. Particularly, those who use child day-care center and surrogate foster home showed more parenting guilt feelings and separation anxiety in Scheffe post-hoc comparison. As a result, it is needed to be improvement of working conditions and policy for nurses` parenting support to continue work.

An approach is presented that permits wide and reversible control of the optical bandwidth of spherical gold nanoparticles assembled on thermoreversible hydrogel colloids for various plasmonic-based thermochromisms. Temperature-dependent swelling and shrinking behaviors of the hydrogel colloids in aqueous systems manipulated assembly structures and optical signals of gold nanoparticles in the hybrid colloids. The optical bandwidths of the hybrid colloids increased with temperature, and thermoreversible bandwidth variations of the hybrid colloids were increased with the diameter of gold nanoparticles (from 15 to 51 nm). These hybrid colloids exhibited multiple colors switching during temperature changes (maximum four colors: wine ↔ violet ↔ dark blue ↔ faint blue). For the hybrid colloids showing a small bandwidth variation, another method was introduced to display different color switching.

The therapeutic benefits of allogeneic hematopoietic stem cell transplantation (allo-HSCT) are primarily derived from graft-versus-leukemia (GvL) that is mediated by mature T cells in donor grafts. Unfortunately, graft-versus-host disease (GvHD) results from immune reactions of these same donor T cells against host tissues and organs after allo-HSCT. Due to this strong association between GvHD and the beneficial GvL, our lab and others have been working on developing effective therapeutic strategies to selectively prevent and treat GvHD without abrogating GvL. Recently we have reported that pharmacologic inhibition of Janus kinases 1/2 (JAK1/JAK2) prevents GvHD by blocking IFNGR and IL6R signaling. Although baricitinib (BARI) and ruxolitinib (RUX) are both JAK1/JAK2 inhibitors with similar potency, BARI was found to be superior to RUX in prevention of GvHD in our mouse models of allo-HSCT. One of our proposed mechanistic pathways by which BARI prevents GvHD is via a robust increase in regulatory T cells (Tregs) which play a pivotal role in controlling GvHD. Since the proliferation and survival of Tregs are mediated through the IL2-JAK1/JAK3-STAT5 signaling pathway and that RUX is a more JAK3 inhibitor, we hypothesized that sparing JAK3 by BARI is critical for this increase of Tregs. To test this hypothesis, we administered BARI to allo-HSCT recipient mice with or without JAK3-specific inhibitor and monitored them for GvHD signs. The mice treated with BARI and iJAK3 had significantly lower Tregs and overall survival rates compared to the mice treated with BARI alone. This data suggests that BARI prevents GvHD by retaining JAK3, thereby increasing Tregs. We have also previously reported that BARI treats established GvHD. However, the mechanisms by which BARI reverses ongoing GvHD remain unclear. Consequently, we hypothesized that BARI not only modulates immune cell functions as we previously reported, but also promotes restoration of GvHD damaged tissues. To test our hypothesis, we delayed the administration of BARI until mice developed clinically apparent GvHD and treated them starting on days 10, 17, or 24 after allo-HSCT. Despite this latency, the day 10 group showed significantly better overall survival (p Since the gastrointestinal (GI) tract is the one of most frequently diagnosed and severely damaged GvHD target organs, we tested the possible mechanistic pathways by which BARI reverses GvHD in the GI tract. We found that Paneth cells and intestinal stem cells which are both involved in maintaining the intestinal barrier integrity are substantially increased in day 10 (p Figure Disclosures DiPersio: Karyopharm Therapeutics: Consultancy; RiverVest Venture Partners Arch Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amphivena Therapeutics: Consultancy, Research Funding; Celgene: Consultancy; Incyte: Consultancy, Research Funding; Macrogenics: Research Funding, Speakers Bureau; WUGEN: Equity Ownership, Patents & Royalties, Research Funding; Magenta Therapeutics: Equity Ownership; Cellworks Group, Inc.: Membership on an entity's Board of Directors or advisory committees; Bioline Rx: Research Funding, Speakers Bureau; NeoImmune Tech: Research Funding. Choi:Daewoong Pharmaceuticals Co., Ltd: Consultancy.

Our data support the feasibility of evaluating fluorine 18 fluorthanatrace as a quantifiable biomarker of poly (adenosine diphosphate–ribose) polymerase expression in clinical trials.

With the advent of a new services environment based on high-speed mobile networks and high-performance mobile devices, users in real life require content-centric services that provide personalized information conveniently and efficiently. These services are defined as ambient services. To implement and support sustainable ambient services, there is a critical need to conduct research regarding practicable models and methodologies. This paper proposes an effective model for ambient services based on the personalization of real-life space. The model consists of Public Info-space, Universal Info-space and Private Info-space. We also show a methodology for implementing the model with currently available techniques in order to prove that the model and methodology constitute an applicable solution to developing true ambient services. Finally, a kind of role-playing game which is built on a real university campus is presented to show the model to be available, where the test bed infrastructure consists of wireless mesh networks and real-time location systems (RTLSes).

During Asian dust events, a relatively high concentration of particulate matter is transported by wind from arid and semi-arid regions, such as the Gobi and Taklamakan deserts, to nearby countries, including China, Korea, and Japan. The dust particles contain various microorganisms, which can affect human health as well as the environmental microbe population. In the current study, we investigated the characteristics of the airborne bacterial community during Asian dust events between February and March 2015 in South Korea. Bacterial diversity indexes such as operational taxonomic units, Chao1 and Inverse Simpson index were increased, along with total 16S rRNA gene copy number during Asian dust events. The bacterial community structure during Asian dust events was clearly distinguishable from that during non-Asian dust days. The genera Bacillus and Modestobacter were increased 3.9- and 2.7-fold, respectively, while Escherichia-Shigella was decreased by 89.8%. A non-metric multidimensional scaling plot with metadata analysis revealed association of particulate matter concentration, but not temperature, humidity or wind speed, with bacterial community structure, suggesting that the newly transported dust particles contain various microorganisms that influence the airborne bacterial environment.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the major curative immunotherapy for hematologic malignancies. The therapeutic benefits of allo-HSCT are primarily derived from an anti-leukemia effect or graft-versus-leukemia (GvL) that is mediated by mature T cells in donor grafts. Unfortunately, these T cells could react against recipient tissues resulting in graft-versus-host disease (GvHD), a life-threatening complication post allo-HSCT. Due to this strong association between GvL and GvHD, developing a more effective therapeutic strategy to selectively suppress GvHD while preserving or enhancing the GvL effects remains a fundamental yet unmet medical need. We have previously published that co-blockade of interferon gamma receptor (IFNGR) and interleukin-6 receptor (IL6R) results in a complete prevention of GvHD (Choi et al., Leukemia, 2018). Moreover, in vivo administration of baricitinib, an inhibitor of Janus kinases 1 and 2 (JAK1/JAK2) which are downstream of IFNGR and IL6R, also prevents GvHD while preserving GvL in our preclinical murine model. The possible mechanistic pathways by which baricitinib mitigates GvHD include robust upregulation of regulatory T cells (Tregs), inhibition of GvHD-inducing Th1/Th2 cell differentiation, an altered T cell trafficking away from GvHD organs, and reduction of antigen presenting cells' allo-reactivity. Given the potent modulatory effect of baricitinib on GvHD and GvL, we next sought to determine the minimum duration of baricitinib treatment for the complete prevention of GvHD. Since we have found that baricitinib significantly increases Tregs during the first two weeks of the treatment, we hypothesized that two weeks of baricitinib administration is sufficient to completely prevent GvHD. We performed allo-HSCT in which B6 (H-2b) T cell-depleted bone marrow cells (5x106) along with pan T cells (5x105) were intravenously injected into lethally irradiated Balb/c mice (H-2d). Baricitinib was subcutaneously administered to the recipient mice once a day (5 days/week) for a period of one, two, three, or four weeks following allo-HSCT. Overall survival rates, clinical GvHD scores, complete blood counts, immunophenotyping of blood cells and histopathological scores were assessed to determine whether the GvHD was prevented. We have found that two to four-week treatment groups demonstrate significantly better overall survival rates, blood count recovery and histopathological scores than vehicle control or the one-week treatment groups, while no such significant differences were observed among the other groups (Fig. A). All of these data suggest that two weeks of baricitinib treatment is sufficient for complete prevention of GvHD. Lastly, we have previously reported that baricitinib reverses established GvHD (Choi et al., Leukemia, 2018) and we have recently found that both JAK1/JAK2 inhibitors, ruxolitinib and baricitinib, significantly enhance human intestinal organoid growth in vitro (Fig. B). Of note, the intestines are frequently diagnosed and severely damaged GvHD target organs in both human patients and our mouse models of GvHD. Thus, we hypothesized that baricitinib not only modulates immune cell functions as described above, but also promotes restoration of tissues damaged by GvHD. To test this hypothesis, we delayed baricitinib administration until mice developed clinically apparent GvHD and administered baricitinib starting on days 10, 17, or 31 after allo-HSCT for a period of two weeks. Despite this latency, the day 10 group showed 100% overall survival rate (5% in control, p In conclusion, our studies demonstrate that baricitinib-induced blockade of IFNGR and IL6R represents a promising therapeutic strategy for both prevention and treatment of GvHD while preserving GvL. Molecular mechanisms underlying baricitinib-mediated reversal of established GvHD are being currently investigated and will be presented. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

A gram-negative bacterium, designated FJY1(T), was isolated from a soil sample obtained from a university campus in South Korea. Examination showed that FJY1(T) was red-pigmented, aerobic, motile, and composed of nonspore-forming rods. This strain grew in a temperature range of 15-37 °C and a pH range of 7-9. Based on 16S rRNA gene sequence similarity, strain FJY1(T) was most closely related to Rufibacter roseus H359(T) and Rufibacter tibetensis 1351(T), with sequence similarities of 95.98 and 95.46 %, respectively. Its major cellular fatty acids were iso-C15:0 (18.16 %) and summed feature 4 (C17:1 iso I and C17:1 anteiso B; 15.17 %). The DNA G+C content of FJY1(T) was 49.7 mol%; its predominant quinone was MK-7; and its major polar lipid was phosphatidylethanolamine. Phylogenetic analysis and analysis of its physiological and biochemical characteristics indicated that this isolate constituted a novel species, for which we propose the name Rufibacter soli sp. nov., with the type strain FJY1(T) (=KCTC 42815(T) = JCM 31024(T)).

We present a simple and industrially accessible method of producing liquid crystalline lipid nanoparticles with various internal structures based on phytantriol, Pluronic F127, and vitamin E acetate. Bilayer vesicles were produced when an ethanolic solution dissolving the lipid components was mixed with deionized water. After the evaporation of ethanol from the aqueous mixture, vesicles were transformed into lipid-filled liquid crystalline nanoparticles with well-defined internal structures such as hexagonal lattices (mostly inverted cubic Pn3m), lined or coiled pattern (inverted hexagonal H2), and disordered structure (inverse microemulsion, L2), depending on the compositions. Further studies suggested that their internal structures were also affected by temperature. The internal structures were characterized from cryo-TEM and small-angle X-ray scattering results. Microcalorimetry studies were performed to investigate the degree of molecular ordering/crystallinity of lipid components within the nanostructures. From the comparative studies, we demonstrated the present method could produce the lipid nanoparticles with similar characteristics to those made from a conventional method. More importantly, the production only requires simple tools for mixing and ethanol evaporation and it is possible to produce 10 kg or so per batch of aqueous lipid nanoparticles dispersions, enabling the large-scale production of the liquid crystalline nanoparticles for various biomedical applications.

Digital paradigms became a reality and now all pay attention on how the world around us is changing and react accordingly. In particular, the increasing importance of computational thinking continues to reframe the dialogue appropriate and effective instruction. Literature instructors are also today being forced to think about 'how to teach', rather than 'what to teach'. Aware of the issues, this paper proposes a new instructional model using big data suitable to be used to teach literary history and provides learners, who had grown up surrounded with an excess of technology and media use in everyday life, opportunities to make literary studies more attractive and easier to understand. Through this, it attempts to explore theoretically educational methodology of studying literary history in order to encourage learners' meaningful participation in classroom.

Computer Aid Education has been considered as a powerful tool for teaching and learning second languages. However, the frequency of its use is considerable low than expectation. It is because of boring and monotonous characters of educational applications. To complete all tasks in educational applications, it is asked great efforts and patient due to lacking fun and amusement. Then for the developers of e-learning applications for language learning, how to add amusement elements on applications is a big deal. In this paper, in order to seek a solution for this, we will show a way to add these elements by gamification of an application for practicing building phrase. The reason we choose phrase building application is that it is mostly difficult to attract leaners' interests in spite of its importance in language learning.

In head and neck squamous cell cancer (HNSCC), four intrinsic subtypes (or groups) have been identified, and each one possesses a unique biology that will require specific treatment strategies. We previously reported that mesenchymal (group 2) tumors exhibit reduced levels of Trop2 expression. In this study, we investigated the functional role of Trop2 in HNSCC and find that loss results in autocrine activation of the EGFR family member ErbB3 via neuregulin-1. Trop2 localizes to both the cell surface and cytosol of HNSCC cells and forms a complex with neuregulin-1, which is predominantly cytosolic. Inactivation of Trop2 increases the concentration of neuregulin-1 at the cell surface where it is cleaved to activate ErbB3. In primary HNSCC, detection of ErbB3 activation was limited to Trop2 negative tumors. An analysis of the Cancer Genome Atlas (TCGA) HNSCC dataset confirms enrichment for ErbB3 activity in mesenchymal tumors. Notably, Trop2 loss triggers sensitivity to anti-ErbB3 antibodies, which results in reduced proliferation and tumorigenic growth of Trop2 negative HNSCC cancer cells. These results uncover a molecular mechanism by which tumor cells control the amount of cell-surface neuregulin-1 available for cleavage and ErbB3 activation. Moreover, we demonstrate that Trop2 is a potential surrogate biomarker to identify tumors with ErbB3 activation and may therefore respond to anti-ErbB3 therapeutics.

Big data analysis is one of the hottest issues in information technology industries. It has been done in quantitative and statistic viewpoints. Observing huge amount of data, it is possible without doubt to establish a model that may predict purchase behaviors of consumers. But this approach can neither explain what brings the consumers to such decisions nor predict future purchase behavior of other product categories. Furthermore, it is not possible to reason about consumers' preferential differences that make choose or avoid certain places and shops. To answer this question, this paper argues that a qualitative analysis based on consumption values will be an alternative, and proposes the conceptual model of extracting consumption values from big data using clothing purchase as a case study.

This article proposes a mobile and augmented reality (AR)-based e- learning model as a form of blended learning strategy customized to the learner, which can be deployed in parallel to face-to-face fieldwork learning. To this end, it looks at theoretical characteristics of such an AR learning system as well as its composition and mode of operation. The type and method of implementing the learning contents are divided into lecture-type formal learning and purely self-directed form of informal learning, and the article goes on to explain the methodology and process of designing learning contents according to each type. The article also discusses what educational potentials a mobile AR-based e-learning system has to offer, and looks at realistic ways to systematically link and integrate it with traditional pedagogy.

In language education, little attention has been paid to the importance of variations of a language. However, knowing standard forms is not sufficient for understanding the target language in real situations. That is why when we learn a target language; we have to pay attention to its linguistic variations. It is believed that e-learning is the most appropriate means of teaching and learning those dialects, because it can offer multiple speaking contexts in the same time and space. This paper gives a brief idea of building e-learning applications that are capable of teaching and learning not only standard, but also variations of a language.

Notch signaling regulates many cellular processes during development and adult tissue renewal. Upon ligand binding, Notch receptors undergo ectodomain shedding followed by γ-secretase-mediated release of the Notch intracellular domain (NICD), which translocates to the nucleus and associates with the DNA binding protein CSL [CBF1/RBPjκ/Su(H)/Lag1] to activate gene expression. Mammalian cells contain four Notch receptors that can have both redundant and specific activities. To monitor activation of specific Notch paralogs in live cells and in real time, we developed luciferase complementation imaging (LCI) reporters for NICD-CSL association and validated them as a specific, robust, and sensitive assay system that enables structure-function and pharmacodynamic analyses. Detailed kinetic analyses of various mechanistic aspects of Notch signaling, including nuclear translocation and inhibition of the activities of γ-secretase and ADAM metalloproteases, as well as agonist- and ligand-dependent activation, were conducted in live cells. These experiments showed that Notch-LCI is an effective approach for characterizing modulators that target Notch signaling and for studying pathway dynamics in normal and disease contexts.