| 1. |
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| 2. |
- 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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| 3. |
- Hong, Yuanyuan, et al.
(författare)
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A Multi-Floor Arrayed Waveguide Grating Based Architecture with Grid Topology for Datacenter Networks
- 2020
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Ingår i: IEEE Access. - 2169-3536 .- 2169-3536. ; 8, s. 107134-107145
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Tidskriftsartikel (refereegranskat)abstract
- This paper proposes a grid topology based passive optical interconnect (POI) architecture that is composed of multiple floors of arrayed waveguide grating routers (AWGRs) to offer high connectivity and scalability for datacenter networks. In the proposed POI signal only needs to pass one AWGR, and thus can avoid the crosstalk accumulation and cascaded filtering effects, which exist in many existing POI architectures based on cascaded AWGRs. Meanwhile, due to high connectivity, the proposed grid topology based POI also has the potential advantage of high reliability. Simulation results validate the network performance. With a proper node degree, the proposed grid topology can achieve acceptable blocking probability. Besides, steady performance is kept when the number of floors increases, indicating good scalability of the proposed POI.
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| 4. |
- Fang, Evandro F., et al.
(författare)
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A research agenda for ageing in China in the 21st century (2nd edition): Focusing on basic and translational research, long-term care, policy and social networks.
- 2020
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Ingår i: Ageing Research Reviews. - : Elsevier BV. - 1568-1637. ; 64
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Tidskriftsartikel (refereegranskat)abstract
- One of the key issues facing public healthcare is the global trend of an increasingly ageing society which continues to present policy makers and caregivers with formidable healthcare and socio-economic challenges. Ageing is the primary contributor to a broad spectrum of chronic disorders all associated with a lower quality of life in the elderly. In 2019, the Chinese population constituted 18 % of the world population, with 164.5 million Chinese citizens aged 65 and above (65+), and 26 million aged 80 or above (80+). China has become an ageing society, and as it continues to age it will continue to exacerbate the burden borne by current family and public healthcare systems. Major healthcare challenges involved with caring for the elderly in China include the management of chronic non-communicable diseases (CNCDs), physical frailty, neurodegenerative diseases, cardiovascular diseases, with emerging challenges such as providing sufficient dental care, combating the rising prevalence of sexually transmitted diseases among nursing home communities, providing support for increased incidences of immune diseases, and the growing necessity to provide palliative care for the elderly. At the governmental level, it is necessary to make long-term strategic plans to respond to the pressures of an ageing society, especially to establish a nationwide, affordable, annual health check system to facilitate early diagnosis and provide access to affordable treatments. China has begun work on several activities to address these issues including the recent completion of the of the Ten-year Health-Care Reform project, the implementation of the Healthy China 2030 Action Plan, and the opening of the National Clinical Research Center for Geriatric Disorders. There are also societal challenges, namely the shift from an extended family system in which the younger provide home care for their elderly family members, to the current trend in which young people are increasingly migrating towards major cities for work, increasing reliance on nursing homes to compensate, especially following the outcomes of the ‘one child policy’ and the ‘empty-nest elderly’ phenomenon. At the individual level, it is important to provide avenues for people to seek and improve their own knowledge of health and disease, to encourage them to seek medical check-ups to prevent/manage illness, and to find ways to promote modifiable health-related behaviors (social activity, exercise, healthy diets, reasonable diet supplements) to enable healthier, happier, longer, and more productive lives in the elderly. Finally, at the technological or treatment level, there is a focus on modern technologies to counteract the negative effects of ageing. Researchers are striving to produce drugs that can mimic the effects of ‘exercising more, eating less’, while other anti-ageing molecules from molecular gerontologists could help to improve ‘healthspan’ in the elderly. Machine learning, ‘Big Data’, and other novel technologies can also be used to monitor disease patterns at the population level and may be used to inform policy design in the future. Collectively, synergies across disciplines on policies, geriatric care, drug development, personal awareness, the use of big data, machine learning and personalized medicine will transform China into a country that enables the most for its elderly, maximizing and celebrating their longevity in the coming decades. This is the 2nd edition of the review paper (Fang EF et al., Ageing Re. Rev. 2015).
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| 5. |
- Chen, Guang, et al.
(författare)
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NeuroIV : Neuromorphic Vision Meets Intelligent Vehicle Towards Safe Driving With a New Database and Baseline Evaluations
- 2022
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Ingår i: IEEE transactions on intelligent transportation systems (Print). - : Institute of Electrical and Electronics Engineers (IEEE). - 1524-9050 .- 1558-0016. ; 23:2, s. 1171-1183
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Tidskriftsartikel (refereegranskat)abstract
- Neuromorphic vision sensors such as the Dynamic and Active-pixel Vision Sensor (DAVIS) using silicon retina are inspired by biological vision, they generate streams of asynchronous events to indicate local log-intensity brightness changes. Their properties of high temporal resolution, low-bandwidth, lightweight computation, and low-latency make them a good fit for many applications of motion perception in the intelligent vehicle. However, as a younger and smaller research field compared to classical computer vision, neuromorphic vision is rarely connected with the intelligent vehicle. For this purpose, we present three novel datasets recorded with DAVIS sensors and depth sensor for the distracted driving research and focus on driver drowsiness detection, driver gaze-zone recognition, and driver hand-gesture recognition. To facilitate the comparison with classical computer vision, we record the RGB, depth and infrared data with a depth sensor simultaneously. The total volume of this dataset has 27360 samples. To unlock the potential of neuromorphic vision on the intelligent vehicle, we utilize three popular event-encoding methods to convert asynchronous event slices to event-frames and adapt state-of-the-art convolutional architectures to extensively evaluate their performances on this dataset. Together with qualitative and quantitative results, this work provides a new database and baseline evaluations named NeuroIV in cross-cutting areas of neuromorphic vision and intelligent vehicle.
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| 6. |
- Liu, Yong, et al.
(författare)
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Deletion Of XIAP reduces the severity of acute pancreatitis via regulation of cell death and nuclear factor-kappa B activity
- 2017
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Ingår i: Cell Death and Disease. - : NATURE PUBLISHING GROUP. - 2041-4889. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Severe acute pancreatitis (SAP) still remains a clinical challenge, not only for its high mortality but the uncontrolled inflammatory progression from acute pancreatitis (AP) to SAP. Cell death, including apoptosis and necrosis are critical pathology of AP, since the severity of pancreatitis correlates directly with necrosis and inversely with apoptosis Therefore, regulation of cell death from necrosis to apoptosis may have practicably therapeutic value. X-linked inhibitor of apoptosis protein (XIAP) is the best characterized member of the inhibitor of apoptosis proteins (IAP) family, but its function in AP remains unclear. In the present study, we investigated the potential role of XIAP in regulation of cell death and inflammation during acute pancreatitis. The in vivo pancreatitis model was induced by the administration of cerulein with or without lipopolysaccharide (LPS) or by the administration of L-arginine in wild-type or XIAP-deficient mice, and ex vivo model was induced by the administration of cerulein+LPS in AR42J cell line following XIAP inhibition. The severity of acute pancreatitis was determined by serum amylase activity and histological grading. XIAP deletion on cell apoptosis, necrosis and inflammatory response were examined. Caspases activities, nuclear factor kappa B (NF-kappa B) activation and receptor-interacting protein kinase1 (RIP1) degradation were assessed by western blot. Deletion of XIAP resulted in the reduction of amylase activity, decrease of NF-kappa B activation and less release of TNF-alpha and IL-6, together with increased caspases activities and RIP1 degradation, leading to enhanced apoptosis and reduced necrosis in pancreatic acinar cells and ameliorated the severity of acute pancreatitis. Our results indicate that deletion of XIAP switches cell death away from necrosis to apoptosis and decreases the inflammatory response, effectively attenuating the severity of AP/SAP. The critical role of XIAP in cell death and inflammation suggests that inhibition of XIAP represents a potential therapeutic strategy for the treatment of acute pancreatitis.
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| 7. |
- Pang, Yun-Jie, et al.
(författare)
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Theoretical Study of the Catalytic Mechanism of the Cu-Only Superoxide Dismutase
- 2023
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Ingår i: Journal of Physical Chemistry B. - 1520-6106 .- 1520-5207. ; 127:21, s. 4800-4807
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Tidskriftsartikel (refereegranskat)abstract
- The catalytic mechanisms for the wild-type and the mutated Cu-only superoxide dismutase were studied using the hybrid density functional B3LYP and a quantum chemical cluster approach. Optimal protonation states of the active site were examined for each stage of the catalytic cycle. For both the reductive and the oxidative half-reactions, the arrival of the substrate O-2(center dot-) was found to be accompanied by a chargecompensating H+ with exergonicities of -15.4 kcal center dot mol and -4.7 kcal center dot mol, respectively. The second-sphere Glu-110 and first-sphere His-93 were suggested to be the transient protonation site for the reductive and the oxidative half-reactions, respectively, which collaborates with the hydrogen bonding water chain to position the substrate near the redox-active copper center. For the reductive half-reaction, the rate-limiting step was found to be the inner-sphere electron transfer from the partially coordinated O-2(center dot-) to Cu-II with a barrier of 8.1 kcal center dot mol. The formed O-2 is released from the active site with an exergonicity of -14.9 kcal center dot mol. For the oxidative half-reaction, the inner-sphere electron transfer from CuI to the partially coordinated O-2(center dot-) was found to be accompanied by the proton transfer from the protonated His-93 and barrierless. The rate-limiting step was found to be the second proton transfer from the protonated Glu-110 to HO2 with a barrier of 7.3 kcal center dot mol. The barriers are reasonably consistent with experimental activities, and a proton-transfer rate-limiting step in the oxidative half-reaction could explain the experimentally observed pH-dependence. For the E110Q CuSOD, Asp-113 was suggested to be likely to serve as the transient protonation site in the reductive half-reaction. The rate-limiting barriers were found to be 8.0 and 8.6 kcal center dot mol, respectively, which could explain the slightly lower performance of E110X mutants. The results were found to be stable, with respect to the percentage of exact exchange in B3LYP.
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| 8. |
- Yang, Xi-Xi, et al.
(författare)
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Theoretical study of the mechanism of the manganese catalase KatB
- 2019
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Ingår i: Journal of Biological Inorganic Chemistry. - : Springer Science and Business Media LLC. - 0949-8257 .- 1432-1327. ; 24:1, s. 103-115
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Tidskriftsartikel (refereegranskat)abstract
- The mechanism of the H2O2 disproportionation catalyzed by the manganese catalase (MnCat) KatB was studied using the hybrid density functional theory B3LYP and the quantum chemical cluster approach. Compared to the previous mechanistic study at the molecular level for the Thermus thermophilus MnCat (TTC), more modern methodology was used and larger models of increasing sizes were employed with the help of the high-resolution X-ray structure. In the reaction pathway suggested for KatB using the Large chemical model, the O-O homolysis of the first substrate H2O2 occurs through a -(1):(1) coordination mode and requires a barrier of 10.9kcal/mol. In the intermediate state of the bond cleavage, two hydroxides form as terminal ligands of the dimanganese cluster at the Mn-2(III,III) oxidation state. One of the two Mn(III)-OH- moieties and a second-sphere tyrosine stabilize the second substrate H2O2 in the second-sphere of the active site via hydrogen bonding interactions. The H2O2, unbound to the metals, is first oxidized into HO2 through a proton-coupled electron transfer (PCET) step with a barrier of 9.5kcal/mol. After the system switches to the triplet surface, the uncoordinated HO2 replaces the product water terminally bound to the Mn(II) and is then oxidized into O-2 spontaneously. Transition states with structural similarities to those obtained for TTC, where -(2)-OH-/O2- groups play important roles, were found to be higher in energy.
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| 9. |
- Bakic, Predrag R., et al.
(författare)
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Artifact reduction in simultaneous tomosynthesis and mechanical imaging of the breast
- 2019
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Ingår i: Medical Imaging 2019 : Physics of Medical Imaging - Physics of Medical Imaging. - : SPIE. - 9781510625433 ; 10948
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Konferensbidrag (refereegranskat)abstract
- Mechanical imaging (MI) uses a pressure sensor array to estimate the stiffness of lesions. Recent clinical studies have suggested that MI combined with digital mammography may reduce false positive findings and negative biopsies by over 30%. Digital breast tomosynthesis (DBT) has been adopted progressively in cancer screening. The tomographic nature of DBT improves lesion visibility by reducing tissue overlap in reconstructed images. For maximum benefit, DBT and MI data should be acquired simultaneously; however, that arrangement produces visible artifacts in DBT images due to the presence of the MI sensor array. We propose a method for reducing artifacts during the DBT image reconstruction. We modified the parameters of a commercial DBT reconstruction engine and investigated the conspicuity of artifacts in the resultant images produced with different sensor orientations. The method was evaluated using a physical anthropomorphic phantom imaged on top of the sensor. Visual assessment showed a reduction of artifacts. In a quantitative test, we calculated the artifact spread function (ASF), and compared the ratio of the mean ASF values between the proposed and conventional reconstruction (termed ASF ratio, RASF). We obtained a mean RASF of 2.74, averaged between two analyzed sensor orientations (45° and 90°). The performance varied with the orientation and the type of sensor structures causing the artifacts. RASF for wide connection lines was larger at 45° than at 90° (5.15 vs. 1.00, respectively), while for metallic contacts RASF was larger at 90° than at 45° (3.31 vs. 2.21, respectively). Future work will include a detailed quantitative assessment, and further method optimization in virtual clinical trials.
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| 10. |
- Bakic, Predrag R., et al.
(författare)
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Pre-processing for image quality improvement in simultaneous DBT and mechanical imaging
- 2020
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Ingår i: Medical Imaging 2020 : Physics of Medical Imaging - Physics of Medical Imaging. - : SPIE. - 1605-7422. - 9781510633919 ; 11312
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Konferensbidrag (refereegranskat)abstract
- Simultaneous digital breast tomosynthesis (DBT) and mechanical imaging (MI) offer the potential to combine anatomic information from DBT with functional information from MI. This makes it possible to associate tissue stiffness with specific anatomic structures in the breast, a combination that can reduce false-positive findings by using the MI data to discriminate between ambiguous lesions in DBT. This, in turn, will reduce the frequency of negative biopsies. Simultaneous imaging requires that the MI sensor array be present during DBT acquisition. This introduces artifacts, since the sensor is attenuating. Previously, we demonstrated that the DBT reconstruction could be modified to reduce sensor conspicuity in DBT images. In this paper, we characterize the relative attenuation of the breast and the sensor, to calculate the artifact reduction in DBT reconstruction. We concentrate on pre-processing DBT projections prior to reconstruction. Using commercially available a DBT system, we have confirmed that the sensor array does not completely attenuate the x-rays. This suggests that a pre-processing method based upon flat fielding can be used to reduce artifacts. In a proof-of-concept study, we performed flat fielding by combining DBT projections of the MI sensor with and without an anthropomorphic breast phantom. Visual evaluation confirmed substantially improved image quality. The artifacts were reduced throughout the image for all sensor elements. Few residual artifacts are noticeable where the phantom thickness decreases. The investigation of additional pre-processing, including beam hardening correction is ongoing. Future work includes quantitative validation, noise stabilization, and method optimization in virtual clinical trials and subsequent patient studies.
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