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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Birney, Ewan, et al.
(författare)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Tidskriftsartikel (refereegranskat)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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| 3. |
- Cao, Lina, et al.
(författare)
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Atomically dispersed iron hydroxide anchored on Pt for preferential oxidation of CO in H-2
- 2019
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Ingår i: Nature. - : NATURE PUBLISHING GROUP. - 0028-0836 .- 1476-4687. ; 565:7741, s. 631-635
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Tidskriftsartikel (refereegranskat)abstract
- Proton-exchange-membrane fuel cells (PEMFCs) are attractive next-generation power sources for use in vehicles and other applications(1), with development efforts focusing on improving the catalyst system of the fuel cell. One problem is catalyst poisoning by impurity gases such as carbon monoxide (CO), which typically comprises about one per cent of hydrogen fuel(2-4). A possible solution is on-board hydrogen purification, which involves preferential oxidation of CO in hydrogen (PROX)(3-7). However, this approach is challenging(8-15) because the catalyst needs to be active and selective towards CO oxidation over a broad range of low temperatures so that CO is efficiently removed (to below 50 parts per million) during continuous PEMFC operation (at about 353 kelvin) and, in the case of automotive fuel cells, during frequent cold-start periods. Here we show that atomically dispersed iron hydroxide, selectively deposited on silica-supported platinum (Pt) nanoparticles, enables complete and 100 per cent selective CO removal through the PROX reaction over the broad temperature range of 198 to 380 kelvin. We find that the mass-specific activity of this system is about 30 times higher than that of more conventional catalysts consisting of Pt on iron oxide supports. In situ X-ray absorption fine-structure measurements reveal that most of the iron hydroxide exists as Fe-1(OH)(x) clusters anchored on the Pt nanoparticles, with density functional theory calculations indicating that Fe-1(OH)(x)-Pt single interfacial sites can readily react with CO and facilitate oxygen activation. These findings suggest that in addition to strategies that target oxide-supported precious-metal nanoparticles or isolated metal atoms, the deposition of isolated transition-metal complexes offers new ways of designing highly active metal catalysts.
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| 4. |
- Chen, Guang, et al.
(författare)
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Neuromorphic Vision Based Multivehicle Detection and Tracking for Intelligent Transportation System
- 2018
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Ingår i: Journal of Advanced Transportation. - : Hindawi Limited. - 0197-6729 .- 2042-3195.
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Tidskriftsartikel (refereegranskat)abstract
- Neuromorphic vision sensor is a new passive sensing modality and a frameless sensor with a number of advantages over traditional cameras. Instead of wastefully sending entire images at fixed frame rate, neuromorphic vision sensor only transmits the local pixel-level changes caused by the movement in a scene at the time they occur. This results in advantageous characteristics, in terms of low energy consumption, high dynamic range, sparse event stream, and low response latency, which can be very useful in intelligent perception systems for modern intelligent transportation system (ITS) that requires efficient wireless data communication and low power embedded computing resources. In this paper, we propose the first neuromorphic vision based multivehicle detection and tracking system in ITS. The performance of the system is evaluated with a dataset recorded by a neuromorphic vision sensor mounted on a highway bridge. We performed a preliminary multivehicle tracking-by-clustering study using three classical clustering approaches and four tracking approaches. Our experiment results indicate that, by making full use of the low latency and sparse event stream, we could easily integrate an online tracking-by-clustering system running at a high frame rate, which far exceeds the real-time capabilities of traditional frame-based cameras. If the accuracy is prioritized, the tracking task can also be performed robustly at a relatively high rate with different combinations of algorithms. We also provide our dataset and evaluation approaches serving as the first neuromorphic benchmark in ITS and hopefully can motivate further research on neuromorphic vision sensors for ITS solutions.
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| 5. |
- Curescu, Calin, 1975-, et al.
(författare)
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Utility-based Adaptive Resource Allocation in Hybrid Wireless Networks
- 2005
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Ingår i: The 2nd IEEE International Conference on Quality of Service in Heterogeneous Wired/Wireless Networks QSHINE,2005. - Conference Proceedings : IEEE Computer Society. ; , s. 44-
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Konferensbidrag (refereegranskat)abstract
- Service availability in wireless networks is highly dependent on efficient resource allocation and guaranteed Quality of Service (QoS) amid overloads and failures. This paper addresses optimal bandwidth allocation in a hybrid network (cellular and ad hoc), where added reach through an ad hoc overlay is combined with the stability and essential services of a cellular network. The paper builds on a near optimal approach in which Resource-Utility functions are used as a means of adaptive delivery of QoS, user differentiation, and maximisation of system level utility. It distinguishes between non-adaptive, semi-adaptive, and fully adaptive applications. First, the global cellular bandwidth allocation (in the presence of multiple routes through ad hoc relays) is cast in terms of a Linear Programming problem. Second, a heuristic algorithm that has far lower computational overhead and accrues at worse 12% less than the utility of the optimal solution is presented. Both algorithms are implemented within a model of a hybrid network on top of the Jsim simulation environment. Comparative tudies are made to show effective load balancing and crash tolerance in the presence of a high traffic overload.
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| 6. |
- Ding, Xue Bing, et al.
(författare)
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Impaired meningeal lymphatic drainage in patients with idiopathic Parkinson’s disease
- 2021
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 27:3, s. 411-418
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Tidskriftsartikel (refereegranskat)abstract
- Animal studies implicate meningeal lymphatic dysfunction in the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease (PD). However, there is no direct evidence in humans to support this role1–5. In this study, we used dynamic contrast-enhanced magnetic resonance imaging to assess meningeal lymphatic flow in cognitively normal controls and patients with idiopathic PD (iPD) or atypical Parkinsonian (AP) disorders. We found that patients with iPD exhibited significantly reduced flow through the meningeal lymphatic vessels (mLVs) along the superior sagittal sinus and sigmoid sinus, as well as a notable delay in deep cervical lymph node perfusion, compared to patients with AP. There was no significant difference in the size (cross-sectional area) of mLVs in patients with iPD or AP versus controls. In mice injected with α-synuclein (α-syn) preformed fibrils, we showed that the emergence of α-syn pathology was followed by delayed meningeal lymphatic drainage, loss of tight junctions among meningeal lymphatic endothelial cells and increased inflammation of the meninges. Finally, blocking flow through the mLVs in mice treated with α-syn preformed fibrils increased α-syn pathology and exacerbated motor and memory deficits. These results suggest that meningeal lymphatic drainage dysfunction aggravates α-syn pathology and contributes to the progression of PD.
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| 7. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 8. |
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| 9. |
- Wang, Zhaoming, et al.
(författare)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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| 10. |
- Xie, Yuan, et al.
(författare)
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Wnt signaling regulates MFSD2A-dependent drug delivery through endothelial transcytosis in glioma
- 2023
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Ingår i: Neuro-Oncology. - : Oxford University Press. - 1522-8517 .- 1523-5866. ; 25:6, s. 1073-1084
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Tidskriftsartikel (refereegranskat)abstract
- Background: Systemic delivery of anti-tumor therapeutic agents to brain tumors is thwarted by the blood-brain barrier (BBB), an organotypic specialization of brain endothelial cells (ECs). A failure of pharmacological compounds to cross BBB is one culprit for the dismal prognosis of glioblastoma (GBM) patients. Identification of novel vascular targets to overcome the challenges posed by the BBB in tumors for GBM treatment is urgently needed.Methods: Temozolomide (TMZ) delivery was investigated in CT2A and PDGFB-driven RCAS/tv-a orthotopic glioma models. Transcriptome analysis was performed on ECs from murine gliomas. Mfsd2a deficient, Cav1 deficient, and Mfsd2a EC-specific inducible mice were developed to study the underlying molecular mechanisms.Results: We demonstrated that inhibiting Wnt signaling by LGK974 could increase TMZ delivery and sensitize glioma to chemotherapy in both murine glioma models. Transcriptome analysis of ECs from murine gliomas revealed that Wnt signaling inhibition enhanced vascular transcytosis as indicated by the upregulation of PLVAP and downregulation of MFSD2A. Mfsd2a deficiency in mice enhances TMZ delivery in tumors, whereas constitutive expression of Mfsd2a in ECs suppresses the enhanced TMZ delivery induced by Wnt pathway inhibition in murine glioma. In addition, Wnt signaling inhibition enhanced caveolin-1 (Cav1)-positive caveolae-mediated transcytosis in tumor ECs. Moreover, Wnt signaling inhibitor or Mfsd2a deficiency fails to enhance TMZ penetration in tumors from Cav1-deficient mice.Conclusions: These results demonstrated that Wnt signaling regulates MFSD2A-dependent TMZ delivery through a caveolae-mediated EC transcytosis pathway. Our findings identify Wnt signaling as a promising therapeutic target to improve drug delivery for GBM treatment.
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