• Title/Summary/Keyword: Novel target

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TAGLN2-mediated actin stabilization at the immunological synapse: implication for cytotoxic T cell control of target cells

  • Na, Bo-Ra;Jun, Chang-Duk
    • BMB Reports
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    • v.48 no.7
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    • pp.369-370
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    • 2015
  • Actin dynamics is critical for the formation and sustainment of the immunological synapse (IS) during T cell interaction with antigen-presenting cells (APC). Thus, many actin regulating proteins are involved in spatial and temporal actin remodeling at the IS. However, little is known whether or how actin stabilizing protein controls IS and the consequent T cell functions. TAGLN2 − an actin-binding protein predominantly expressed in T cells − displays a novel function to stabilize cortical F-actin, thereby augmenting F-actin contents at the IS, and acquiring leukocyte function-associated antigen-1 activation following T cell activation. TAGLN2 also competes with cofilin to protect F-actin in vitro and in vivo. During cytotoxic T cell interaction with cancer cells, the expression level of TAGLN2 at the IS correlates with the T cell adhesion to target cancer cells and production of lytic granules such as granzyme B and perforin, thus expressing cytotoxic T cell function. These findings identify a novel function for TAGLN2 as an actin stabilizing protein that is essential for stable immunological synapse formation, thereby regulating T cell immunity. [BMB Reports 2015; 48(7): 369-370]

Development of a Reliability Index using Design, Development and Production Information (설계, 개발 및 양산 정보를 활용한 신뢰성 지수 개발)

  • Kim, Sung Kyu;Park, Jung Won;Kim, Yong Soo
    • Journal of Korean Society for Quality Management
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    • v.43 no.3
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    • pp.373-382
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    • 2015
  • Purpose: In this paper, we developed a reliability index (RI) to efficiently compare reliability of products based on the design, development and production information such as reliability tests, quality, product life-cycle management. RI also can be applied to reliability prediction of a novel product as well as comparison evaluation among existing products. Methods: For evaluating RI, we proposed evaluation process which is composed of five steps. Target modules are selected based on warranty data and correlation analysis. Scores of selected target modules are calculated by scoring function. Finally, weights of RI model are determined by optimization method. Results: This paper presented an empirical analysis based on failure data of mobile devices. In this case study, we demonstrated that there is a direct correlation between evaluated RI and field failure probability of each product. Conclusion: We proposed the index for comprehensive and effective assessment of product reliability level. From the procedure of this study, we expected to be applied for reliability estimation of novel products and deduction of field failure-related factors.

A Network-Based Model for Estimating the Market Share of a High-Speed Rail System in the Korean NW-SE Corridor (네트워크 기반모델을 이용한 서울-부산간 고속철도 개통 후의 교통수단별 시장점유율 예측)

  • Gang-Len Chang
    • Proceedings of the KOR-KST Conference
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    • 2003.02a
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    • pp.127-150
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    • 2003
  • This research presents a novel application of static traffic assignment methods, but with a variable time value, for estimating the market share of a high-speed rail (HSR) in the NW-SE corridor of Korea which is currently served by the airline (AR), conventional rail (CR), and highway (HWY) modes. The proposed model employs the time-space network structure to capture the interrelations among all competing transportation modes, and to reflect their supply- and demand-sides constraints as well as interactions through properly formulated link-node structures. The embedded cost function for each network link offers the flexibility for incorporating all associated factors, such as travel time and fare, in the model computation, and enables the use of a distribution rather than a constant to represent the time-value variation among all transportation mode users. To realistically capture the tripmakers' value-of-time (VOT) along the target area, a novel method for VOT calibration has been developed with aggregate demand information and key system performance data from the target area. Under the assumption that intercity tripmakers often have nearly "perfect" travel information, one can solve the market share of each mode after operations of HSR for each O-D pair under the time-dependent demand with state-of-the-art traffic assignment. Aside from estimating new market share, this paper also investigated the impacts of HSR on other existing transportation modes.

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3-D High Resolution Ultrasonic Transmission Tomography and Soft Tissue Differentiation

  • Kim Tae-Seong
    • Journal of Biomedical Engineering Research
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    • v.26 no.1
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    • pp.55-63
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    • 2005
  • A novel imaging system for High-resolution Ultrasonic Transmission Tomography (HUTT) and soft tissue differentiation methodology for the HUTT system are presented. The critical innovation of the HUTT system includes the use of sub-millimeter transducer elements for both transmitter and receiver arrays and multi-band analysis of the first-arrival pulse. The first-arrival pulse is detected and extracted from the received signal (i.e., snippet) at each azimuthal and angular location of a mechanical tomographic scanner in transmission mode. Each extracted snippet is processed to yield a multi-spectral vector of attenuation values at multiple frequency bands. These vectors form a 3-D sinogram representing a multi-spectral augmentation of the conventional 2-D sinogram. A filtered backprojection algorithm is used to reconstruct a stack of multi-spectral images for each 2-D tomographic slice that allow tissue characterization. A novel methodology for soft tissue differentiation using spectral target detection is presented. The representative 2-D and 3-D HUTT images formed at various frequency bands demonstrate the high-resolution capability of the system. It is shown that spherical objects with diameter down to 0.3㎜ can be detected. In addition, the results of soft tissue differentiation and characterization demonstrate the feasibility of quantitative soft tissue analysis for possible detection of lesions or cancerous tissue.

Applications of CRISPR technologies to the development of gene and cell therapy

  • Chul-Sung Park;Omer Habib;Younsu Lee;Junho K. Hur
    • BMB Reports
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    • v.57 no.1
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    • pp.2-11
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    • 2024
  • Advancements in gene and cell therapy have resulted in novel therapeutics for diseases previously considered incurable or challenging to treat. Among the various contributing technologies, genome editing stands out as one of the most crucial for the progress in gene and cell therapy. The discovery of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) and the subsequent evolution of genetic engineering technology have markedly expanded the field of target-specific gene editing. Originally studied in the immune systems of bacteria and archaea, the CRISPR system has demonstrated wide applicability to effective genome editing of various biological systems including human cells. The development of CRISPR-based base editing has enabled directional cytosine-to-thymine and adenine-to-guanine substitutions of select DNA bases at the target locus. Subsequent advances in prime editing further elevated the flexibility of the edit multiple consecutive bases to desired sequences. The recent CRISPR technologies also have been actively utilized for the development of in vivo and ex vivo gene and cell therapies. We anticipate that the medical applications of CRISPR will rapidly progress to provide unprecedented possibilities to develop novel therapeutics towards various diseases.

Survivin, a Promising Gene for Targeted Cancer Treatment

  • Shamsabadi, Fatemeh T;Eidgahi, Mohammad Reza Akbari;Mehrbod, Parvaneh;Daneshvar, Nasibeh;Allaudin, Zeenathul Nazariah;Yamchi, Ahad;Shahbazi, Majid
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.8
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    • pp.3711-3719
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    • 2016
  • Drawbacks of conventional cancer treatments, with lack of specificity and cytotoxicity using current approaches, underlies the necessity for development of a novel approach, gene-directed cancer therapy. This has provided novel technological opportunities in vitro and in vivo. This review focuses on a member of an apoptosis inhibitor family, survivin, as a valuable target. Not only the gene but also its promoter are applicable in this context. This article is based on a literature survey, with especial attention to RNA interference as well as tumor-specific promoter action. The search engine and databases utilized were Science direct, PubMed, MEDLINE and Google. In addition to cell-cycle modulation, apoptosis inhibition, interaction in cell-signaling pathways, cancer-selective expression, survivin also may be considered as specific target through its promoter as a novel treatment for cancer. Our purpose in writing this article was to create awareness in researchers, emphasizing relation of survivin gene expression to potential cancer treatment. The principal result and major conclusion of this manuscript are that survivin structure, biological functions and applications of RNA interference systems as well as tumor-specific promoter activity are of major interest for cancer gene therapy.

Novel Dioxygenases, HIF-α Specific Prolyl-hydroxylase and Asparanginyl-hydroxylase: O2 Switch for Cell Survival

  • Park, Hyun-Sung
    • Toxicological Research
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    • v.24 no.2
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    • pp.101-107
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    • 2008
  • Studies on hypoxia-signaling pathways have revealed novel Fe(II) and $\alpha$-ketoglutarate-dependent dioxygenases that hydroxylate prolyl or asparaginyl residues of a transactivator, Hypoxia-Inducible $Factor-\alpha(HIF-\alpha)$ protein. The recognition of these unprecedented dioxygenases has led to open a new paradigm that the hydroxylation mediates an instant post-translational modification of a protein in response to the changes in cellular concentrations of oxygen, reducing agents, or $\alpha$-ketoglutarate. Activity of $HIF-\alpha$ is repressed by two hydroxylases. One is $HIF-\alpha$ specific prolyl-hydroxylases, referred as prolyl-hydroxylase domain(PHD). The other is $HIF-\alpha$ specific asparaginyl-hydroxylase, referred as factor-inhibiting HIF-1(FIH-1). The facts (i) that many dioxygenases commonly use molecular oxygen and reducing agents during detoxification of xenobiotics, (ii) that detoxification reaction produces radicals and reactive oxygen species, and (iii) that activities of both PHD and FIH-1 are regulated by the changes in the balance between oxygen species and reducing agents, imply the possibility that the activity of $HIF-\alpha$ can be increased during detoxification process. The importance of $HIF-\alpha$ in cancer and ischemic diseases has been emphasized since its target genes mediate various hypoxic responses including angiogenesis, erythropoiesis, glycolysis, pH balance, metastasis, invasion and cell survival. Therefore, activators of PHDs and FIH-1 can be potential anticancer drugs which could reduce the activity of HIF, whereas inhibitors, for preventing ischemic diseases. This review highlights these novel dioxygenases, PHDs and FIH-1 as specific target against not only cancers but also ischemic diseases.

Small RNA Transcriptome of Hibiscus Syriacus Provides Insights into the Potential Influence of microRNAs in Flower Development and Terpene Synthesis

  • Kim, Taewook;Park, June Hyun;Lee, Sang-gil;Kim, Soyoung;Kim, Jihyun;Lee, Jungho;Shin, Chanseok
    • Molecules and Cells
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    • v.40 no.8
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    • pp.587-597
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    • 2017
  • MicroRNAs (miRNAs) are essential small RNA molecules that regulate the expression of target mRNAs in plants and animals. Here, we aimed to identify miRNAs and their putative targets in Hibiscus syriacus, the national flower of South Korea. We employed high-throughput sequencing of small RNAs obtained from four different tissues (i.e., leaf, root, flower, and ovary) and identified 33 conserved and 30 novel miRNA families, many of which showed differential tissuespecific expressions. In addition, we computationally predicted novel targets of miRNAs and validated some of them using 5' rapid amplification of cDNA ends analysis. One of the validated novel targets of miR477 was a terpene synthase, the primary gene involved in the formation of disease-resistant terpene metabolites such as sterols and phytoalexins. In addition, a predicted target of conserved miRNAs, miR396, is SHORT VEGETATIVE PHASE, which is involved in flower initiation and is duplicated in H. syriacus. Collectively, this study provides the first reliable draft of the H. syriacus miRNA transcriptome that should constitute a basis for understanding the biological roles of miRNAs in H. syriacus.

Identification of Novel Target Proteins of Cyclic GMP Signaling Pathways Using Chemical Proteomics

  • Kim, Eui-Kyung;Park, Ji-Man
    • BMB Reports
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    • v.36 no.3
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    • pp.299-304
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    • 2003
  • For deciphering the cyclic guanosine monophosphate (cGMP) signaling pathway, we employed chemical proteomics to identify the novel target molecules of cGMP. We used cGMP that was immobilized onto agarose beads with linkers directed at three different positions of cGMP. We performed a pull-down assay using the beads as baits on tissue lysates and identified 9 proteins by MALDI-TOF (Matrix-Assisted Laser Desorption/Ionization Time-of-Flight) mass spectrometry. Some of the identified proteins were previously known cGMP targets, including cGMP-dependent protein kinase and cGMP-stimulated phosphodiesterase. Surprisingly, some of the co-precipitated proteins were never formerly reported to associate with the cGMP signaling pathway. The competition binding assays showed that the interactions are not by nonspecific binding to either the linker or bead itself, but by specific binding to cGMP. Furthermore, we observed that the interactions are highly specific to cGMP against other nucleotides, such as cyclic adenosine monophosphate (cAMP) and 5'-GMP, which are structurally similar to cGMP. As one of the identified targets, MAPK1 was confirmed by immunoblotting with an anti-MAPK1 antibody. For further proof, we observed that the membrane-permeable cGMP (8-bromo cyclic GMP) stimulated mitogen-activated protein kinase 1 signaling in the treated cells. Our present study suggests that chemical proteomics can be a very useful and powerful technique for identifying the target proteins of small bioactive molecules.

A Novel Approach on $H_{\infty}$-LTR Controller Design ($H_{\infty}$-LTR 제어기 설계의 새로운 접근방법)

  • Lhee, Chin-Gook;Park, Jae-Sam;Ahn, Hyun-Sik;Kim, Do-Hyun
    • Journal of the Korean Institute of Telematics and Electronics S
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    • v.36S no.2
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    • pp.38-45
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    • 1999
  • In this paper, A novel approach on $H_{\infty}-LTR$ design scheme is presented. The proposed scheme provides a design toll which can trade-off the recovery error against the control input. In the first stage, Kalman filter is designed to shape the loop to satisfy the required performance specifications. The designed Kalman filter, together with the plant transfer function, is used as a target transfer function. In the second stage, sensitivity function weighted $H_{\infty}-LTR$suboptimal LTR is designed to recover the target loop transfer function. Simulation results of LQG/LTR, $H_{\infty}-LTR$are compared to demonstrate the good property of the proposed scheme.

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