| 1491. |
- Kopparapu, Pradeep Kumar, et al.
(författare)
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Epigenetic silencing of miR-26A1 in chronic lymphocytic leukemia and mantle cell lymphoma: Impact on EZH2 expression. : Epigenetic inactivation of miR - 26A1 in CLL and MCL
- 2016
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Ingår i: Epigenetics. - : Informa UK Limited. - 1559-2294 .- 1559-2308. ; 11:5, s. 335-343
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Tidskriftsartikel (refereegranskat)abstract
- Downregulation of miR26A1 has been reported in various B-cell malignancies; however, the mechanism behind its deregulation remains largely unknown. We investigated miR26A1 methylation and expression levels in a well-characterized series of chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). From 450K methylation arrays, we first observed miR26A1 (cg26054057) as uniformly hypermethylated in MCL (n=24) (all >75%), while CLL (n=18) showed differential methylation between prognostic subgroups. Extended analysis using pyrosequencing confirmed our findings and real-time quantitative PCR verified low miR26A1 expression in both CLL (n=70) and MCL (n=38) compared to normal B-cells. Notably, the level of miR26A1 methylation predicted outcome in CLL, with higher levels seen in poor-prognostic, IGHV-unmutated CLL. Since EZH2 was recently reported as a target for miR26A1, we analyzed the expression levels of both miR26A1 and EZH2 in primary CLL samples and observed an inverse correlation. By overexpression of miR26A1 in CLL and MCL cell lines, reduced EZH2 protein levels were observed using both Western blot and flow cytometry. In contrast, methyl-inhibitor treatment led to upregulated miR26A1 expression with a parallel decrease of EZH2 expression. Finally, increased levels of apoptosis were observed in miR26A1-overexpressing cell lines, further underscoring the functional relevance of miR26A1. In summary, we propose that epigenetic silencing of miR26A1 is required for the maintenance of increased levels of EZH2, which in turn translate into a worse outcome, as shown in CLL, highlighting miR26A1 as a tumor suppressor miRNA.
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| 1492. |
- Kosar, M, et al.
(författare)
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The human nucleoporin Tpr protects cells from RNA-mediated replication stress
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 3937-
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Tidskriftsartikel (refereegranskat)abstract
- Although human nucleoporin Tpr is frequently deregulated in cancer, its roles are poorly understood. Here we show that Tpr depletion generates transcription-dependent replication stress, DNA breaks, and genomic instability. DNA fiber assays and electron microscopy visualization of replication intermediates show that Tpr deficient cells exhibit slow and asymmetric replication forks under replication stress. Tpr deficiency evokes enhanced levels of DNA-RNA hybrids. Additionally, complementary proteomic strategies identify a network of Tpr-interacting proteins mediating RNA processing, such as MATR3 and SUGP2, and functional experiments confirm that their depletion trigger cellular phenotypes shared with Tpr deficiency. Mechanistic studies reveal the interplay of Tpr with GANP, a component of the TREX-2 complex. The Tpr-GANP interaction is supported by their shared protein level alterations in a cohort of ovarian carcinomas. Our results reveal links between nucleoporins, DNA transcription and replication, and the existence of a network physically connecting replication forks with transcription, splicing, and mRNA export machinery.
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| 1493. |
- Kovi, Kiran Kumar, 1980-, et al.
(författare)
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Semi-isotropic surface etching of diamond using a Faraday cage
- 2015
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Ingår i: Diamond and related materials. - 0925-9635 .- 1879-0062. ; 58, s. 185-189
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Tidskriftsartikel (refereegranskat)abstract
- Etching of diamond is one of the most important process steps to realize diamond based devices. Isotropic etching in diamond yielding a high etch rate is challenging owing to its material properties. In the current study, single-crystalline diamond is etched using a Faraday cage that acts as the mask to attain semi-isotropic etching. An oxygen/chlorine plasma discharge with a pressure of 10 mTorr is used. The etching process is optimized by varying the applied plasma power, and the substrate bias together with varying parameters such as the thickness of the mask, the mask-to-diamond surface distance and the diameter of the holes in the mask. After optimization, semi-isotropic etched surface profiles up to a depth of 5 μm with an etch rate of 80 nm/min and surface roughness close to that of the unetched surface are achieved.
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| 1494. |
- Kristan, Matej, et al.
(författare)
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The Visual Object Tracking VOT2016 Challenge Results
- 2016
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Ingår i: COMPUTER VISION - ECCV 2016 WORKSHOPS, PT II. - Cham : SPRINGER INT PUBLISHING AG. - 9783319488813 - 9783319488806 ; , s. 777-823
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Konferensbidrag (refereegranskat)abstract
- The Visual Object Tracking challenge VOT2016 aims at comparing short-term single-object visual trackers that do not apply pre-learned models of object appearance. Results of 70 trackers are presented, with a large number of trackers being published at major computer vision conferences and journals in the recent years. The number of tested state-of-the-art trackers makes the VOT 2016 the largest and most challenging benchmark on short-term tracking to date. For each participating tracker, a short description is provided in the Appendix. The VOT2016 goes beyond its predecessors by (i) introducing a new semi-automatic ground truth bounding box annotation methodology and (ii) extending the evaluation system with the no-reset experiment.
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| 1495. |
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| 1496. |
- Kuderna, Lukas F. K., et al.
(författare)
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Identification of constrained sequence elements across 239 primate genomes
- 2024
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 625:7996, s. 735-742
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Tidskriftsartikel (refereegranskat)abstract
- Noncoding DNA is central to our understanding of human gene regulation and complex diseases1,2, and measuring the evolutionary sequence constraint can establish the functional relevance of putative regulatory elements in the human genome3,4,5,6,7,8,9. Identifying the genomic elements that have become constrained specifically in primates has been hampered by the faster evolution of noncoding DNA compared to protein-coding DNA10, the relatively short timescales separating primate species11, and the previously limited availability of whole-genome sequences12. Here we construct a whole-genome alignment of 239 species, representing nearly half of all extant species in the primate order. Using this resource, we identified human regulatory elements that are under selective constraint across primates and other mammals at a 5% false discovery rate. We detected 111,318 DNase I hypersensitivity sites and 267,410 transcription factor binding sites that are constrained specifically in primates but not across other placental mammals and validate their cis-regulatory effects on gene expression. These regulatory elements are enriched for human genetic variants that affect gene expression and complex traits and diseases. Our results highlight the important role of recent evolution in regulatory sequence elements differentiating primates, including humans, from other placental mammals.
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| 1497. |
- Kumar, Abhinav, et al.
(författare)
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A Biocompatible Synthetic Lung Fluid Based on Human Respiratory Tract Lining Fluid Composition.
- 2017
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Ingår i: Pharmaceutical research. - : Springer Science and Business Media LLC. - 0724-8741 .- 1573-904X. ; 34:12, s. 2454-2465
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To characterise a biorelevant simulated lung fluid (SLF) based on the composition of human respiratory tract lining fluid. SLF was compared to other media which have been utilized as lung fluid simulants in terms of fluid structure, biocompatibility and performance in inhalation biopharmaceutical assays.METHODS: The structure of SLF was investigated using cryo-transmission electron microscopy, photon correlation spectroscopy and Langmuir isotherms. Biocompatibility with A549 alveolar epithelial cells was determined by MTT assay, morphometric observations and transcriptomic analysis. Biopharmaceutical applicability was evaluated by measuring the solubility and dissolution of beclomethasone dipropionate (BDP) and fluticasone propionate (FP), in SLF.RESULTS: SLF exhibited a colloidal structure, possessing vesicles similar in nature to those found in lung fluid extracts. No adverse effect on A549 cells was apparent after exposure to the SLF for 24 h, although some metabolic changes were identified consistent with the change of culture medium to a more lung-like composition. The solubility and dissolution of BDP and FP in SLF were enhanced compared to Gamble's solution.CONCLUSION: The SLF reported herein constitutes a biorelevant synthetic simulant which is suitable to study biopharmaceutical properties of inhalation medicines such as those being proposed for an inhaled biopharmaceutics classification system.
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| 1498. |
- Kumar, A., et al.
(författare)
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A Scalable Feedback Mechanism for Distributed Nullforming with Phase-Only Adaptation
- 2015
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Ingår i: IEEE Transactions on Signal and Information Processing over Networks. - : Institute of Electrical and Electronics Engineers Inc.. - 2373-776X. ; 1:1, s. 58-70
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Tidskriftsartikel (refereegranskat)abstract
- This paper considers a problem of distributed nullforming, in which multiple wireless transmitters steer a null toward a designated receiver by only adjusting their carrier phases. Since each transmitter transmits at full power, the system maximizes 'power pooling' gains for cooperative communication or jamming, while simultaneously protecting a designated receiver. Analysis in a noiseless setting shows that, while the received power at the designated receiver, as a function of the transmitted phases, is nonconvex with multiple critical points, all of its local minima are also global minima. This implies that a null can be formed using a distributed, scalable protocol based on gradient descent: each transmitter adapts its phase based only on aggregate feedback broadcast by the receiver (so that feedback overhead does not increase with the number of transmitters), along with an estimate of its own channel gain (which can be obtained, e.g., via reciprocity). Simulations show that the convergence rate actually improves with the number of transmitters, and that the algorithm is robust to noise, substantial channel estimation errors, and oscillator drift.
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| 1499. |
- Kumar, Ashok, et al.
(författare)
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Binding of Cu(II)-poly(N-isopropylacrylamide/vinylimidazole) copolymer to histidine-tagged protein: a surface plasmon resonance study.
- 2003
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 19:3, s. 865-871
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Tidskriftsartikel (refereegranskat)abstract
- The thermoresponsive copolymer of N-isopropylacrylamide (NIPAM) with 1-vinylimidazole (VI), poly(NIPAM-VI), synthesized by radical polymerization has been used to purify the histidine-tagged green flourescent protein (His-tag GFP) from recombinant E. coli by metal-chelate affinity precipitation. The purified protein was immobilized on the BIAcore sensor chip by carbodiimide coupling. Affinity binding of the Cu(II)-loaded copolymer, poly(NIPAM-VI), to the His-tag GFP-immobilized surface was monitored by surface-plasmon-resonance (SPR) measurements. Complete recovery of the metal copolymer from the surface was achieved with either using the monomer displacer, 200 mM imidazole buffer, or the polymeric displacer, copolymer of poly(NIPAM-VI) (26 mol % VI). The conformation of the copolymer was a critical factor for the metal interactions and hence displacement of the metal copolymer. With the proposed conformation of protein-like copolymers (Wahlund, P.-O.; Galaev, I. Yu.; Kazakov, S. A.; Lozinsky, V. I.; Mattiasson, B. Macromol. Biosci. 2002, 2, 33.), the SPR study confirmed the prediction of exposed imidazole groups in the poly(NIPAM-VI). The complete elution of the affinity-bound metal copolymer was achieved with protein-like copolymer (imidazole groups exposed to the outer solution), and no recovery was obtained with IMAC nonbound copolymer fraction (imidazole groups unexposed). The SPR measurement showed a sharp phase transition of affinity adsorbed thermoresponsive Cu(II)-poly(NIPAM-VI) copolymer at 32 C, thus proposing a sensitive way to determine lower critical solution temperature.
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| 1500. |
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