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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. |
- Gao, Yipeng, et al.
(författare)
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Research on the Security of Visual Reasoning CAPTCHA
- 2021
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Ingår i: PROCEEDINGS OF THE 30TH USENIX SECURITY SYMPOSIUM. - : USENIX ASSOC. - 9781939133243 ; , s. 3291-3308
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Konferensbidrag (refereegranskat)abstract
- CAPTCHA is an effective mechanism for protecting computers from malicious bots. With the development of deep learning techniques, current mainstream text-based CAPTCHAs have been proven to be insecure. Therefore, a major effort has been directed toward developing image-based CAPTCHAs, and image-based visual reasoning is emerging as a new direction of such development. Recently, Tencent deployed the Visual Turing Test (VTT) CAPTCHA. This appears to have been the first application of a visual reasoning scheme. Subsequently, other CAPTCHA service providers (Geetest, NetEase, Dingxiang, etc.) have proposed their own visual reasoning schemes to defend against bots. It is, therefore, natural to ask a fundamental question: are visual reasoning CAPTCHAs as secure as their designers expect? This paper presents the first attempt to solve visual reasoning CAPTCHAs. We implemented a holistic attack and a modular attack, which achieved overall success rates of 67.3% and 88.0% on VTT CAPTCHA, respectively. The results show that visual reasoning CAPTCHAs are not as secure as anticipated; this latest effort to use novel, hard AI problems for CAPTCHAs has not yet succeeded. Based on the lessons we learned from our attacks, we also offer some guidelines for designing visual CAPTCHAs with better security.
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| 4. |
- Li, Ting, et al.
(författare)
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Total genetic contribution assessment across the human genome
- 2021
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Quantifying the overall magnitude of every single locus' genetic effect on the widely measured human phenome is of great challenge. We introduce a unified modelling technique that can consistently provide a total genetic contribution assessment (TGCA) of a gene or genetic variant without thresholding genetic association signals. Genome-wide TGCA in five UK Biobank phenotype domains highlights loci such as the HLA locus for medical conditions, the bone mineral density locus WNT16 for physical measures, and the skin tanning locus MC1R and smoking behaviour locus CHRNA3 for lifestyle. Tissue-specificity investigation reveals several tissues associated with total genetic contributions, including the brain tissues for mental health. Such associations are driven by tissue-specific gene expressions, which share genetic basis with the total genetic contributions. TGCA can provide a genome-wide atlas for the overall genetic contributions in each particular domain of human complex traits. Quantifying the effects of individual loci on the human phenome is a challenging task. Here, the authors introduce a modelling technique, TGCA, that assesses total genetic contribution per locus and apply this to UK Biobank phenotype domains, revealing top loci and links to tissue-specific gene expression.
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| 5. |
- Yang, Zhijian, et al.
(författare)
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Genetic Landscape of the ACE2 Coronavirus Receptor
- 2022
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Ingår i: Circulation. - : Ovid Technologies (Wolters Kluwer Health). - 0009-7322 .- 1524-4539. ; 30:SUPPL 1, s. 36-36
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Tidskriftsartikel (refereegranskat)abstract
- Background: SARS-CoV-2, the causal agent of COVID-19, enters human cells using the ACE2 (angiotensin-converting enzyme 2) protein as a receptor. ACE2 is thus key to the infection and treatment of the coronavirus. ACE2 is highly expressed in the heart and respiratory and gastrointestinal tracts, playing important regulatory roles in the cardiovascular and other biological systems. However, the genetic basis of the ACE2 protein levels is not well understood.Methods: We have conducted the largest genome-wide association meta-analysis of plasma ACE2 levels in >28 000 individuals of the SCALLOP Consortium (Systematic and Combined Analysis of Olink Proteins). We summarize the cross-sectional epidemiological correlates of circulating ACE2. Using the summary statistics-based high-definition likelihood method, we estimate relevant genetic correlations with cardiometabolic phenotypes, COVID-19, and other human complex traits and diseases. We perform causal inference of soluble ACE2 on vascular disease outcomes and COVID-19 severity using mendelian randomization. We also perform in silico functional analysis by integrating with other types of omics data.Results: We identified 10 loci, including 8 novel, capturing 30% of the heritability of the protein. We detected that plasma ACE2 was genetically correlated with vascular diseases, severe COVID-19, and a wide range of human complex diseases and medications. An X-chromosome cis-protein quantitative trait loci-based mendelian randomization analysis suggested a causal effect of elevated ACE2 levels on COVID-19 severity (odds ratio, 1.63 [95% CI, 1.10-2.42]; P=0.01), hospitalization (odds ratio, 1.52 [95% CI, 1.05-2.21]; P=0.03), and infection (odds ratio, 1.60 [95% CI, 1.08-2.37]; P=0.02). Tissue- and cell type-specific transcriptomic and epigenomic analysis revealed that the ACE2 regulatory variants were enriched for DNA methylation sites in blood immune cells.Conclusions: Human plasma ACE2 shares a genetic basis with cardiovascular disease, COVID-19, and other related diseases. The genetic architecture of the ACE2 protein is mapped, providing a useful resource for further biological and clinical studies on this coronavirus receptor.
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| 6. |
- Zhang, Jia, et al.
(författare)
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Transport Layer Engineering Toward Lower Threshold for Perovskite Lasers
- 2023
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Ingår i: Advanced Materials. - : WILEY-V C H VERLAG GMBH. - 0935-9648 .- 1521-4095. ; 35:30
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Tidskriftsartikel (refereegranskat)abstract
- Charge-transport layers are essential for achieving electrically pumped perovskite lasers. However, their role in perovskite lasing is not fully understood. Here, the role of charge-transport layers on the lasing actions of perovskite films is explored by investigating the amplified spontaneous emission (ASE) thresholds. A largely reduced ASE threshold and enhanced ASE intensity is demonstrated by introducing an additional hole transport layer poly(triaryl amine) (PTAA). It is shown that the key role of the PTAA layer is to accelerate the hot-carrier cooling process by extracting holes in perovskites. With reduced hot holes, the Auger recombination loss is largely suppressed, resulting in decreased ASE threshold. This argument is further supported by the fact that the ASE threshold can be further reduced from 25.7 to 7.2 mu J cm(-2) upon switching the pumping wavelength from 400 to 500 nm to directly avoid excess hot-hole generation. This work exemplifies how to further reduce the ASE threshold with transport layer engineering through hot-hole manipulation. This is critical to maintaining the excellent gain properties of perovskites when integrating them into electrical devices, paving the way for electrically pumped perovskite lasers.
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