Paired-domination in inflated graphs

2003-2004 > Academic research: refereed > Publication in refereed journalAccepted ManuscriptPublishe

Vascular Proteomics Reveal Novel Proteins Involved in SMC Phenotypic Change: OLR1 as a SMC Receptor Regulating Proliferation and Inflammatory Response

Neointimal hyperplasia of vascular smooth muscle cells (VSMC) plays a critical role in atherosclerotic plaque formation and in-stent restenosis, but the underlying mechanisms are still incompletely understood. We performed a proteomics study to identify novel signaling molecules organizing the VSMC hyperplasia. The differential proteomics analysis in a balloon- induced injury model of rat carotid artery revealed that the expressions of 44 proteins are changed within 3 days post injury. The combination of cellular function assays and a protein network analysis further demonstrated that 27 out of 44 proteins constitute key signaling networks orchestrating the phenotypic change of VSMC from contractile to epithelial-like synthetic. Among the list of proteins, the in vivo validation specifically revealed that six proteins (Rab 15, ITR, OLR1, PDH beta, PTP epsilon) are positive regulators for VSMC hyperplasia. In particular, the OLR1 played dual roles in the VSMC hyperplasia by directly mediating oxidized LDL-induced monocyte adhesion via NF-kappa B activation and by assisting the PDGF-induced proliferation/migration. Importantly, OLR1 and PDGFR beta were associated in close proximity in the plasma membrane. Thus, this study elicits the protein network organizing the phenotypic change of VSMC in the vascular injury diseases such as atherosclerosis and discovers OLR1 as a novel molecular link between the proliferative and inflammatory responses of VSMCs.1133Ysciescopu

A Definitive Signal of Multiple Supersymmetry Breaking

If the lightest observable-sector supersymmetric particle (LOSP) is charged and long-lived, then it may be possible to indirectly measure the Planck mass at the LHC and provide a spectacular confirmation of supergravity as a symmetry of nature. Unfortunately, this proposal is only feasible if the gravitino is heavy enough to be measured at colliders, and this condition is in direct conflict with constraints from big bang nucleosynthesis (BBN). In this work, we show that the BBN bound can be naturally evaded in the presence of multiple sectors which independently break supersymmetry, since there is a new decay channel of the LOSP to a goldstino. Certain regions of parameter space allow for a direct measurement of LOSP decays into both the goldstino and the gravitino at the LHC. If the goldstino/gravitino mass ratio is measured to be 2, as suggested by theory, then this would provide dramatic verification of the existence of multiple supersymmetry breaking and sequestering. A variety of consistent cosmological scenarios are obtained within this framework. In particular, if an R symmetry is imposed, then the gauge-gaugino-goldstino interaction vertices can be forbidden. In this case, there is no bound on the reheating temperature from goldstino overproduction, and thermal leptogenesis can be accommodated consistently with gravitino dark matter.Comment: 10 pages, 5 figures, title changed to match the version published in JHE

Generation and chromosome mapping of expressed sequence tags (ESTs) from a human infant thymus

In an effort to identify novel genes that are expressed differentially in an infant thymus, we constructed an oligo-d(T) primed cDNA library from a human infant thymus followed by single-run partial sequencing to generate expressed sequence tags (ESTs). Characterization of more than 1400 sequences enabled us to convert human thymus transcripts into 1223 useful ESTs. These ESTs consisted of 613 (50.1%) showing homology to known human genes, 51 (4.2%) matching to genes from other species, 289 (23.6%) matching ESTs of unknown functions, and 182 (14.9%) being novel transcripts. The expression profile of an infant thymus features a high number of genes related to cell division-DNA synthesis and gene-protein expression, indicating the active growth stage of an infant thymus. To identify the chromosomal localization of 43 thymus ESTs, PCR-based mapping was performed using a human-rodent somatic cell hybrid or radiation hybrid mapping panel. The results indicated that several novel genes were determined to be located in the vicinity of previously mapped disease loci; histidinemia loci, plasminogen Tochigi disease loci, Ehlers-Danlos syndrome, hypertriglyceridemia, thyroid resistance locus, ocular albinism, galactosemia, porphyria variegata, Charcot-Marie-tooth disease, FEOM (fibrosis of extraocular muscles), Prader-Willi syndrome.published_or_final_versio

The SWELL1-LRRC8 complex regulates endothelial AKT-eNOS signaling and vascular function

The endothelium responds to numerous chemical and mechanical factors in regulating vascular tone, blood pressure, and blood flow. The endothelial volume-regulated anion channel (VRAC) has been proposed to be mechanosensitive and thereby sense fluid flow and hydrostatic pressure to regulate vascular function. Here, we show that the leucine-rich repeat-containing protein 8a, LRRC8A (SWELL1), is required for VRAC in human umbilical vein endothelial cells (HUVECs). Endothelial LRRC8A regulates AKT-endothelial nitric oxide synthase (eNOS) signaling under basal, stretch, and shear-flow stimulation, forms a GRB2-Cav1-eNOS signaling complex, and is required for endothelial cell alignment to laminar shear flow. Endothelium-restricte

Managing changes initiated by industrial big data technologies : a technochange management model

With the adoption of Internet of Things and advanced data analytical technologies in manufacturing firms, the industrial sector has launched an evolutionary journey toward the 4th industrial revolution, or so called Industry 4.0. Industrial big data is a core component to realize the vision of Industry 4.0. However, the implementation and usage of industrial big data tools in manufacturing firms will not merely be a technical endeavor, but can also lead to a thorough management reform. By means of a comprehensive review of literature related to Industry 4.0, smart manufacturing, industrial big data, information systems (IS) and technochange management, this paper aims to analyze potential changes triggered by the application of industrial big data in manufacturing firms, from technological, individual and organizational perspectives. Furthermore, in order to drive these changes more effectively and eliminate potential resistance, a conceptual technochange management model was developed and proposed. Drawn upon theories reported in literature of IS technochange management, this model proposed four types of interventions that can be used to copy with changes initiated by industrial big data technologies, including human process intervention, techno-structural intervention, human resources management intervention and strategic intervention. This model will be of interests and value to practitioners and researchers concerned with business reforms triggered by Industry 4.0 in general and by industrial big data technologies in particular

Rose Bengal sensitized bilayered photoanode of nano-crystalline TiO–CeO for dye-sensitized solar cell application

There are two traditional ways to read Kant’s claim that every event necessarily has a cause: the weaker every-event some-cause (WCP) and the stronger same-cause same-effect (SCP) causal principles. The debate on whether and where he subscribes to the SCP has focused on the Analogies in the Critique of Pure Reason (Guyer, Allison, and Watkins) and on the Metaphysical Foundations of Natural Science (Friedman). By analysing the arguments and conclusions of both the Analogies and the Postulates, as well as the two Latin principles non datur casus and non datur fatum that summarise their results, I will argue that the SCP is actually demonstrated in the Postulates section of the First Critique

Dynamic Regulation of Oct1 during Mitosis by Phosphorylation and Ubiquitination

Transcription factor Oct1 regulates multiple cellular processes. It is known to be phosphorylated during the cell cycle and by stress, however the upstream kinases and downstream consequences are not well understood. One of these modified forms, phosphorylated at S335, lacks the ability to bind DNA. Other modification states besides phosphorylation have not been described.We show that Oct1 is phosphorylated at S335 in the Oct1 DNA binding domain during M-phase by the NIMA-related kinase Nek6. Phospho-Oct1 is also ubiquitinated. Phosphorylation excludes Oct1 from mitotic chromatin. Instead, Oct1(pS335) concentrates at centrosomes, mitotic spindle poles, kinetochores and the midbody. Oct1 siRNA knockdown diminishes the signal at these locations. Both Oct1 ablation and overexpression result in abnormal mitoses. S335 is important for the overexpression phenotype, implicating this residue in mitotic regulation. Oct1 depletion causes defects in spindle morphogenesis in Xenopus egg extracts, establishing a mitosis-specific function of Oct1. Oct1 colocalizes with lamin B1 at the spindle poles and midbody. At the midbody, both proteins are mutually required to correctly localize the other. We show that phospho-Oct1 is modified late in mitosis by non-canonical K11-linked polyubiquitin chains. Ubiquitination requires the anaphase-promoting complex, and we further show that the anaphase-promoting complex large subunit APC1 and Oct1(pS335) interact.These findings reveal mechanistic coupling between Oct1 phosphorylation and ubquitination during mitotic progression, and a role for Oct1 in mitosis

Genetic determinants of co-accessible chromatin regions in activated T cells across humans.

Over 90% of genetic variants associated with complex human traits map to non-coding regions, but little is understood about how they modulate gene regulation in health and disease. One possible mechanism is that genetic variants affect the activity of one or more cis-regulatory elements leading to gene expression variation in specific cell types. To identify such cases, we analyzed ATAC-seq and RNA-seq profiles from stimulated primary CD4+ T cells in up to 105 healthy donors. We found that regions of accessible chromatin (ATAC-peaks) are co-accessible at kilobase and megabase resolution, consistent with the three-dimensional chromatin organization measured by in situ Hi-C in T cells. Fifteen percent of genetic variants located within ATAC-peaks affected the accessibility of the corresponding peak (local-ATAC-QTLs). Local-ATAC-QTLs have the largest effects on co-accessible peaks, are associated with gene expression and are enriched for autoimmune disease variants. Our results provide insights into how natural genetic variants modulate cis-regulatory elements, in isolation or in concert, to influence gene expression