408 research outputs found
Data of methylome and transcriptome derived from human dilated cardiomyopathy
No full textAbstractAlterations in DNA methylation and gene expression have been implicated in the development of human dilated cardiomyopathy (DCM). Differentially methylated probes (DMPs) and differentially expressed genes (DEGs) were identified between the left ventricle (LV, a pathological locus for DCM) and the right ventricle (RV, a proxy for normal hearts). The data in this DiB are for supporting our report entitled “Methylome analysis reveals alterations in DNA methylation in the regulatory regions of left ventricle development genes in human dilated cardiomyopathy” (Bong-Seok Jo, In-Uk Koh, Jae-Bum Bae, Ho-Yeong Yu, Eun-Seok Jeon, Hae-Young Lee, Jae-Joong Kim, Murim Choi, Sun Shim Choi, 2016) [1]
Predictable Dual-View Hashing
No full textWe propose a Predictable Dual-View Hashing (PDH) algorithm which embeds proximity of data samples in the original spaces. We create a cross-view hamming space with the ability to compare information from previously incomparable domains with a notion of 'predictability'. By performing comparative experimental analysis on two large datasets, PASCAL-Sentence and SUN-Attribute, we demonstrate the superiority of our method to the state-of-the-art dual-view binary code learning algorithms. Copyright 2013 by the author(s).N
SAND AND SILTY-SAND SOIL STABILIZATION USING BACTERIAL ENZYME INDUCED CALCITE PRECIPITATION (BEICP)
No full textThis paper examines the bio-derived stabilization of sand-only or sand-plus-silt soils using an extracted bacterial enzyme application to achieve induced calcite precipitation (ICP). As compared to conventional microbial induced calcite precipitation (MICP) methods, which use intact bacterial cells, this strategy which uses free urease catalysts to secure bacterial enzyme induced calcite precipitation (BEICP) appears to offer an improved means of biostabilizing silty-sand soils as compared to that of MICP processing. Several benefits may possibly be achieved with this BEICP approach, including bio-safety, environmental, and geotechnical improvements. Notably, the BEICP biostabilization results presented by this paper demonstrate: 1) higher rates of catalytic urease activity, 2) a wider range of application with sand-plus-silt soil applications bearing low plasticity properties, and 3) the ability to retain higher levels of soil permeability after BEICP processing. Comparative BEICP versus MICP results for sand-only systems are presented, along with BEICP-based results for stabilized soil mixtures at 90-10 and 80-20 percentile sand-silt ratios. This BEICP methodâ s ability to obtain unconfined compressive strength (UCS) results in excess of 1,000 kPa with sand-plus-silt soil mixtures is particularly noteworthy.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author
Molecular Fate Determinants in Embryonic and Adult Neural Stem Cells
No full textThe molecular signals specifying neuronal, glial or multipotent precursors in the developing and adult central nervous system (CNS) are largely unknown. Radial glial cells have recently been discovered as major precursor population generating neurons or glial cells in separate lineages in the developing CNS. Towards this aim to identify the key molecular determinants for neurogenic versus gliogenic fate in radial glial cells I used a novel method to selectively enrich neurogenic or non-neurogenic radial glia and compared their gene expression to adult subependymal zone (SEZ) precursors in vitro and in vivo. The expression profile of the transcription factors Olig2 and Pax6 were particularly intriguing. Olig2 was 67 fold higher in multipotent compared to neuronal or glial precursors, while Pax6 showed strongest expression in neuronal precursors. I therefore focused further on the functional analysis of Pax6 and Olig2 in neural stem cell in vitro and in vivo. Interference with Olig2 in neural stem cells in vitro revealed its role in self-renewal. In adult neural stem cells of the SEZ overexpression of Olig2 promoted oligodendrocyte formation. Pax6, in contrast, proved to be a very potent neurogenic determinant since neurogenesis is not only Pax6-dependent in neural stem cells in vitro, but also in adult neural stem cell in vivo.
Taken together, these results demonstrate a pathway combining transcription factors of dorsal and ventral regions that is activated in a specific lineage progression of adult neural stem cells in vitro and in vivo. Most importantly also in regard to therapeutic approaches, this work revealed the molecular mechanisms to direct adult neural stem cells towards a specific cell fate, neuronal or oligodendroglial
Event-related brain response to visual cues in individuals with Internet gaming disorder: relevance to attentional bias and decision-making
No full textThis study investigated attentional bias toward game-related cues in Internet gaming disorder (IGD) using electrophysiological markers of late positive potential (LPP) and identifying the sources of LPP. In addition, the association between LPP and decision-making ability was investigated. The IGD (n = 40) and healthy control (HC; n = 39) participants viewed a series of game-related and neutral pictures, while their event-related potentials (ERPs) were recorded. LPPs were calculated as the mean amplitudes between 400 and 700 ms at the centro-parietal (CP3, CP1, Cpz, CP2, and CP4) and parietal (P3, P1, Pz, P2, and P4) electrode sites. The source activations of LPP were estimated using standardized low-resolution brain electromagnetic tomography (sLORETA). In addition, decision-making ability was evaluated by the Cambridge Gambling Task. Higher LPP amplitudes were found for game-related cues in the IGD group than in the HC group. sLORETA showed that the IGD group was more active in the superior and middle temporal gyri, which are involved in social perception, than in the HC group, whereas it was less active in the frontal area. Individuals with IGD have deficits in decision-making ability. In addition, in the HC group, the lower the LPP when looking at the game-related stimuli, the better the quality of decision-making, but not in the IGD group. Enhanced LPP amplitudes are associated with emotional arousal to gaming cues and decision-making deficits in IGD. In addition, source activities suggest that patients with IGD perceive game-related cues as social stimuli. LPP can be used as a neurophysiological marker of IGD. © 2021, The Author(s).1
Senescent tumor cells building three-dimensional tumor clusters
No full textCellular senescence, a permanent cell-cycle arrest, is a common yet intriguing phenomenon, in which its beneficial significance for biological organisms has only begun to be explored. Among others, senescent cells are able to transform tissue structures around them. Tumor cells, whose hallmark is their ability to proliferate indefinitely, are not free from the phenomenon. Here, we report a remarkable observation where senescent cells in a dense mono-layer of breast cancer colony act as aggregating centers for non-senescent cells in their vicinity. Consequently, the senescent cells actively form localized 3D cell-clusters in a confluent 2D tumor layer. The biophysical mechanism underpinning the surprising phenomenon primarily involves mitotic cell-rounding, dynamic and differential cell attachments, and cellular chemotaxis. By incorporating these few biophysical factors, we were able to recapitulate the experimental observation via a cellular Potts Model.© The Author(s) 201
Recent follow-up negotiations on WTO government procurement agreement and some policy issues for Korea
No full text선후진국을 막론하고 정부조달은 전통적으로 자국 경제사회의 발전을 위해 각국 정부가 다양한 정책목적과 용도로 사용할 수 있는 매우 유력하고 중요한 정책수단으로 인식되어 왔고 또 그렇게 사용되어 왔다. 그 결과 이 시장은 GATT 출범 후 근 30년 동안 무역자유화의 사각지대에 머물러 왔다. 그러나 WTO 출범 이후 정부조달시장의 개방이 빠른 속도로 진행되고 있다. 이 글은 최근의 정부조달시장 개방문제를 둘러싼 WTO 중심의 논의 및 협상동향과 주요이슈를 살펴보고, 우리나라의 정부조달시잔 개방현황을 고찰한 다음, 가속화되고 있는 개방체제 하에서 우리나라 조달행정의 당면과제를 도출하고 있다. 이 가운데 특히 정부조달협정(GPA) 적용대상기관의 확대와 공기업 민영화 대상기관의 제외문제, 지속적인 투명성 제고, 외국의 조달시장에 대한 국내기업의 진출 확대 지원, 지역간/양국간 협정 차원에서의 협력 강화, 조달시장 개방 관련 교육훈련의 강화 등이 중요한 과제로 부각되고 있음을 밝히고, 좀더 적극적인 자세로 정부조달시장 개방 문제에 대응하는 것이 정부조달의 효율성과 투명성 확보, 통상마찰의 해소 차원에서 긴요함을 강조하고 있다. Almost all governments of either advanced or developing countries have long recognized the importance of government procurement as the most effective took of government policy aimed at fostering domestic industries, and have used this tool with an explicit or implicit intent of protection. As a result, the issue of putting government procurement under the jurisdiction of GATT had been long neglected until the Plurilateral Agreement on Government Procurement(GPA) was concluded in the form of "codes" at Tokyo Round, and revised considerably at Uruguay Round. But as the interest in increasing efficiency in government and public services grows, and consequently as the privatization of state-owned enterprises and contracting-out of government services traditionally reserved for public entities accelerate, the issue of further opening-up of government procurement markets has attracted ever greater attention recently and has been put on top of the multilateral negotiation agenda. In terms of market openness and the ongoing efforts to increase transparency of procurement rules and procedures, Korea has performed reasonably well. But it still faces a number of policy problems particularly in areas such as widening the coverage of GPA, excepting privatized companies from the list of entities covered, sustained effort to increase transparency, supporting domestic firms to enter foreign government procurement markets, and providing adequate education and training for agencies and officials concerned. Toward all of these issues, the author recommends that the Korean government take more active policy stance in view of their immensely beneficial effects on national welfare, anti-corruption efforts, and the avoidance of trade disputes
Nystagmus only with fixation in the light: a rare central sign due to cerebellar malfunction
No full text© 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.Fixation nystagmus refers to the nystagmus that appears or markedly increases with fixation. While relatively common in infantile (congenital) nystagmus, acquired fixation nystagmus is unusual and has been ascribed to lesions involving the cerebellar nuclei or the fibers projecting from the cerebellum to the brainstem. We aimed to report the clinical features of patients with acquired fixation nystagmus and discuss possible mechanisms using a model simulation and diagnostic significance. We describe four patients with acquired fixation nystagmus that appears or markedly increases with visual fixation. All patients had lesions involving the cerebellum or dorsal medulla. All patients showed direction-changing gaze-evoked nystagmus, impaired smooth pursuit, and decreased vestibular responses on head-impulse tests. The clinical implication of fixation nystagmus is that it may occur in central lesions that impair both smooth pursuit and the vestibulo-ocular reflex (VOR) but without creating a spontaneous nystagmus in the dark. We develop a mathematical model that hypothesizes that fixation nystagmus reflects a central tone imbalance due to abnormal function in cerebellar circuits that normally optimize the interaction between visual following (pursuit) and VOR during attempted fixation. Patients with fixation nystagmus have central lesions involving the cerebellar circuits that are involved in visual–vestibular interactions and normally eliminate biases that cause a spontaneous nystagmus.N
Sexually dimorphic behavior, neuronal activity, and gene expression in Chd8-mutant mice
No full textAutism spectrum disorders (ASDs) are four times more common in males than in females, but the underlying mechanisms are poorly understood. We characterized sexually dimorphic changes in mice carrying a heterozygous mutation in Chd8 (Chd8+/N2373K) that was first identified in human CHD8 (Asn2373LysfsX2), a strong ASD-risk gene that encodes a chromatin remodeler. Notably, although male mutant mice displayed a range of abnormal behaviors during pup, juvenile, and adult stages, including enhanced mother-seeking ultrasonic vocalization, enhanced attachment to reunited mothers, and isolation-induced self-grooming, their female counterparts do not. This behavioral divergence was associated with sexually dimorphic changes in neuronal activity, synaptic transmission, and transcriptomic profiles. Specifically, female mice displayed suppressed baseline neuronal excitation, enhanced inhibitory synaptic transmission and neuronal firing, and increased expression of genes associated with extracellular vesicles and the extracellular matrix. Our results suggest that a human CHD8 mutation leads to sexually dimorphic changes ranging from transcription to behavior in mice. © 2018, The Author(s
BRD4/nuclear PD-L1/RelB circuit is involved in the stemness of breast cancer cells
No full textAbstract Background Breast cancer (BC) is the most common cancer diagnosed in women worldwide. BC stem cells (BCSCs) have been known to be involved in the carcinogenesis of the breast and contribute to therapeutic resistance. The programmed death-ligand 1 (PD-L1) expression of BC correlated with a poor prognosis. Immunotherapies that target PD-L1 have great potential and have been successful when applied to cancer treatment. However, whether PD-L1 regulates BCSC formation is unknown. Methods BCSCs were enriched by serum-free suspension culture. The properties of BCSCs were examined by mammosphere formation assay, CD44+/Cd24−, aldehyde dehydrogenase (ALDH) assay, CSC marker analysis, and mammosphere growth assay. To elucidate the functions of bromodomain-containing protein 4 (BRD4), nuclear PD-L1, and RelB proteins in the stemness of BCSCs, mammosphere formation was examined using BRD4 inhibitor and degrader, PD-L1 degrader, and RelB inhibitor. The antitumor function of 3',4',7,8-tetrahydroxyflavone (THF), a specific BRD4 inhibitor, was studied through in vivo tumor model and mouse studies, and the protein levels of c-Myc, PD-L1, and RelB were examined in tumor model under THF treatment. Results BRD4 was upregulated in breast CSCs and regulates the stemness of BCs. The downregulation of BRD4 using BRD4 PROTAC, ARV-825, and BRD4 inhibitor, (+)-JQ1, inhibits mammosphere formation and reduces the levels of breast CSC markers (CD44+/CD24− and ALDH1), stem cell marker genes, and mammosphere growth. BRD4 inhibitor (JQ1) and degrader (ARV825) downregulate membrane and nuclear fractions of PD-L1 through the inhibition of PD-L1 transcript levels. The knockdown of PD-L1 inhibits mammosphere formation. Verteporfin, a PD-L1 degrader, inhibits the transcripts and protein levels of PD-L1 and downregulates the transcript and protein levels of RelB. Calcitriol, a RelB inhibitor, and the knockdown of RelB using si-RelB regulate mammosphere formation through interleukin-6 (IL-6) expression. THF is a natural product and a potent selective BRD4 inhibitor, inhibits mammosphere formation, and reduces the levels of CD44+/CD24− and mammosphere growth by downregulating c-Myc, PD-L1, and RelB. 3',4',7,8-THF shows tumoricidal activity and increased levels of CD3+CD4+ and CD3+CD8+ T-cells in the tumor and tumor-draining lymph nodes (TDLNs) in the murine tumor model using 4T1 and MC38 cells. Conclusions The results show the first evidence of the essential role of the BRD4/nuclear PD-L1/RelB axis in breast CSC formation. The nuclear PD-L1 regulates RelB, and the RelB/p65 complex induces IL6 and breast CSC formation. Targeting nuclear PD-L1 represents a potential and novel tool for immunotherapies of intractable BC. Video Abstrac
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