877 research outputs found
sj-pdf-1-jcb-10.1177_0271678X231185507 - Supplemental material for Intermittent hypoxia protects against hypoxic-ischemic brain damage by inducing functional angiogenesis
No full textSupplemental material, sj-pdf-1-jcb-10.1177_0271678X231185507 for Intermittent hypoxia protects against hypoxic-ischemic brain damage by inducing functional angiogenesis by Yuying Guan, Yakun Gu, Haitao Shao, Wei Ma, Gaifen Li, Mengyuan Guo, Qianqian Shao, Yuning Li, Yingxia Liu, Chaoyu Wang, Zhengming Tian, Jia Liu and Xunming Ji in Journal of Cerebral Blood Flow & Metabolism</p
Author Correction: A shared neural basis underlying psychiatric comorbidity
No full textCorrection to: Nature Medicine. Published online 24 April 2023. In the version of this article initially published, the STRATIFY data also included cohort data from the ESTRA consortium, though this was not acknowledged in the author list and the section in Methods on the Stratify dataset. The Methods are now updated, and the author list is amended to combine the STRATIFY and ESTRA consortium names and to include the following authors: Marina Bobou, M. John Broulidakis, Betteke Maria van Noort, Zuo Zhang, Lauren Robinson, Nilakshi Vaidya, Jeanne Winterer, Yuning Zhang, Sinead King, Hervé Lemaître, Ulrike Schmidt, Julia Sinclair, Argyris Stringaris and Sylvane Desrivières. The STRATIFY and ESTRA consortia are now combined to list Marina Bobou, M. John Broulidakis, Betteke Maria van Noort, Zuo Zhang, Lauren Robinson, Nilakshi Vaidya, Jeanne Winterer, Yuning Zhang, Sinead King, Gareth J. Barker, Arun L. W. Bokde, Hervé Lemaître, Frauke Nees, Dimitri Papadopoulos Orfanos, Ulrike Schmidt, Julia Sinclair, Argyris Stringaris, Henrik Walter, Robert Whelan, Sylvane Desrivières and Gunter Schumann as members, and the IMAGEN consortium is updated to also include Sylvane Desrivières. Affiliations, author contributions and acknowledgements have been updated to reflect the new authorship, and all changes have been made in the HTML and PDF versions of the article
Flourishing chancelloriids from the Cambrian Kaili Biota of South China
No full textNational Natural Science Foundation of China 10.13039/501100001809Guizhou Province Graduate Research FundGuizhou Bureau of Science and TechnologyTalent base project of Guizhou ProvinceState Key Laboratory of Palaeobiology and Stratigraphy 50110001227
Author Correction: A shared neural basis underlying psychiatric comorbidity
No full textCorrection to: Nature Medicine https://doi.org/10.1038/s41591-023-02317-4. Published online 24 April 2023. In the version of this article initially published, the STRATIFY data also included cohort data from the ESTRA consortium, though this was not acknowledged in the author list and the section in Methods on the Stratify dataset. The Methods are now updated, and the author list is amended to combine the STRATIFY and ESTRA consortium names and to include the following authors: Marina Bobou, M. John Broulidakis, Betteke Maria van Noort, Zuo Zhang, Lauren Robinson, Nilakshi Vaidya, Jeanne Winterer, Yuning Zhang, Sinead King, Hervé Lemaître, Ulrike Schmidt, Julia Sinclair, Argyris Stringaris and Sylvane Desrivières. The STRATIFY and ESTRA consortia are now combined to list Marina Bobou, M. John Broulidakis, Betteke Maria van Noort, Zuo Zhang, Lauren Robinson, Nilakshi Vaidya, Jeanne Winterer, Yuning Zhang, Sinead King, Gareth J. Barker, Arun L. W. Bokde, Hervé Lemaître, Frauke Nees, Dimitri Papadopoulos Orfanos, Ulrike Schmidt, Julia Sinclair, Argyris Stringaris, Henrik Walter, Robert Whelan, Sylvane Desrivières and Gunter Schumann as members, and the IMAGEN consortium is updated to also include Sylvane Desrivières. Affiliations, author contributions and acknowledgements have been updated to reflect the new authorship, and all changes have been made in the HTML and PDF versions of the article.</p
From the headwater to the delta: A synthesis of the basin-scale sediment load regime in the Changjiang River
No full textMany large rivers in the world delivers decreasing sediment loads to coastal oceans owing to reductions in sediment yield and disrupted sediment deliver. Understanding the sediment load regime is a prerequisite of sediment management and fluvial and deltaic ecosystem restoration. This work examines sediment load changes across the Changjiang River basin based on a long time series (1950–2017) of sediment load data stretching from the headwater to the delta. We find that the sediment loads have decreased progressively throughout the basin at multiple time scales. The sediment loads have decreased by ~96% and ~74% at the outlets of the upper basin and entire basin, respectively, in 2006–2017 compared to 1950–1985. The hydropower dams in the mainstem have become a dominant cause of the reduction, although downstream channel erosion causes moderate sediment load recovery. The basin-scale sediment connectivity has declined as the upper river is progressively dammed, the middle-lower river is leveed and river-lake interplay weakens. The middle-lower river has changed from a slight depositional to a severe erosional environment, from a sediment transport conduit to a new sediment source zone, and from a transport-limited to a supply-limited condition. These low-level sediment loads will likely persist in the future considering the cumulative dam trapping and depleted channel erosion. As a result, substantial hydro-morphological changes have occurred that affect the water supply, flood mitigation, and the aquatic ecosystem. The findings and lessons in this work can shed light on other large river systems subject to intensified human interference.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Coastal Engineerin
Rezension/Review/Mapitio: Yuning Shen. 2018. Transitivität und Verbvalenz im Swahili. [Transitivity and Verb Valence in Swahili/Uelekezi na Mpangilio wa Vitenzi katika Lugha ya Kiswahili]. Köln: Rüdiger Köppe, 104 pp., ISBN 978-3-89645-712-7.
No full textYuning Shen’s study deals with transitivity and verb valency in Kiswahili using a corpus-based approach. The author relates the methods used and results with previous studies dealing with the same topic, namely Whiteley (1968), Abdulaziz (1996) and Olejarnik (2005). He uses the meta-function-rank-matrix (MF/R) from Chinese to point out the fallacy of adopting such a matrix from one language and imposing it on another. Using the parts of speech annotation TreeTagger (Schmid 1994, 1995) to examine previous verb classifications, the author discusses the divergent use of concepts such as verb radicals, verb stems and verb bases as used in different theoretical approaches.Kitabu hiki cha Yuning Shen kinahusu uelekezi na mpangilio wa vitenzi katika lugha ya Kiswahili kwa kutumia mkabala wenye msingi wa kopasi ya kiisimu. Mwandishi anazihusisha mbinu zilizotumika na matokeo yake na kazi za utafiti zilizotangulia zilizoshughulikia mada hiyo yaani Whiteley (1968), Abdulaziz (1996), na Olejarnik (2005). Shen anatumia mkabala wa mpangilio wa viwango tofauti vya matumizi ya lugha (meta-function-rank-matrix, MF/R) iliyotumika kwa utafiti wa lugha ya Kichina kwa ajili ya kuonesha udhaifu wa mkabala huo kwani unaiga mfumo unaofanya kazi katika lugha moja na kuutumia kwa lugha nyingine bila kuzingatia kuwa lugha ni tofauti. Kwa kutumia njia ya matawi ya kutenganisha vipashio vya maneno (TreeTagger) iliyobuniwa na Schmid (1994, 1995) kwa lengo la kuchunguza njia za awali za kuainisha vitenzi, mwandishi anayajadili matumizi yanayotofautiana ya dhana mbalimbali kama vile viini vya vitenzi, mashina ya vitenzi, na mizizi ya vitenzi jinsi ambavyo zimetumika katika mikabala mbalimbali ya kinadharia
Neural–genetic–environmental evidence for a disease factor in mental and physical health multimorbidity
No full textIncreasing evidence reveals the presence of multimorbidity across physical and mental disorders. A general disease factor (d factor) has been recently identified to capture the shared liability across these conditions, yet its biological basis remains poorly understood. Here, using data from the UK Biobank, we reveal the d factor's neural, genetic, and environmental underpinnings. We show that the d factor is associated with extreme negative deviations in grey matter volume and white matter microstructure. A genome-wide association study identifies its genetic loci and correlations with unhealthy lifestyle, anthropometric measures, and mood-related phenotypes. Furthermore, Mendelian randomization suggests a causal effect of living environmental deprivation on the d factor. Mediation analysis further reveals that the d factor links this environmental adversity to individual differences in brain structure. Our findings establish a multi-level biological characterization of general disease liability, connecting environmental, genetic, and neural factors and inform transdiagnostic approaches to prevention and treatment
Foreign Language Teachers' Beliefs and Practices in Language Education: What to Teach and How to Teach
No full textThis dissertation is a combination of two manuscripts. By using autoethnography in manuscript one, this study first reflects on my learning English as a foreign language journey and the influences that brought to my life. The seven stories in this study cover many aspects of foreign language education, including teaching contents, teaching methods, and teacher preparation. Through the lens of autoethnography, I will further explore factors that influence foreign language education. Through detailed analysis, I discover language learning is not isolated. Foreign language teaching and learning will be influenced by economy, politics, cultures, and society. Based on these findings, I ask many thought-provoking questions on foreign language education, such as teaching contents and teaching methods.
Manuscript two is traditional qualitative research using ethnographic methods. I use in-depth interviews to explore teachers' beliefs and practices of one supervisor and three foreign language teachers. I first present findings on their beliefs and practices in foreign language teaching and learning, including changes and challenges in the division's language education and foreign language teachers' beliefs and practices and their alignment with the ACTFL Standards. I will also use the ACTFL Standards as a lens to analyze how their beliefs and practices match with the 5Cs: Communication, cultures, connections, comparisons, communities. Finally, I will provide suggestions for future similar studies.Doctor of PhilosophyThis dissertation is a combination of two manuscripts. Manuscript one reflects on the author's journey learning English as a foreign language and the influences that had brought to her life. The seven stories in this study cover many aspects in foreign language education, including teaching content, teaching methods, and teachers' preparation. The author further explores the causes and other related factors in foreign language education. Through detailed analysis, the author discovers language learning is not isolated. Foreign language teaching and learning will be influenced by economy, politics, cultures, and society. Manuscript two is traditional qualitative research using ethnographic methods. The author uses interviews to explore teachings beliefs and practices of one supervisor and three foreign language teachers. She provides suggestions for future studies
Shi wang mo mu xi bao liu yu ji yin zu fei wen ding xing
No full textPh.D.Retinoblastoma protein（RB）is a tumor suppressor that is known for its roles in regulating transcription and cell proliferation. It is encoded by the RB1 gene. Biallelic RB1 mutation will lead to inactivation of the RB protein and it was first found in a children eye cancer called retinoblastoma. Inactivated RB can also be found in other cancer such as lung cancer and breast cancer. Additional roles of RB have been found in human cells including regulating cell migration, preventing mitochondrial defects, and regulating multiple signaling pathways. Recent studies identify key roles of RB mutations that would lead to chromosome instability and aneuploidy. RB was found to localize on DNA double strand breaks (DSBs). It co-localized with γH2AX, a histone H2A protein phosphorylated on serine 139, which is an important marker of DSBs. In my PhD study, I have demonstrated the RB function in resection of DNA DSBs, an important step in the DSB repair pathways, in human U2OS cells. Our results suggest an important role of RB in promoting the initiation of DSB end resection during DSB repair. In addition, we have also identified that RB could promote homologous recombination (HR) and classical non-homologous end joining (NHEJ), the two major DSB repair pathways. On the contrary, RB knocked-down cells showed elevated level of micro-homology end joining (MMEJ), another DSB repair pathway involving a small degree of DNA end resection. Our results suggested that the roles of RB in regulating DNA DSB repair pathways are independent to its roles in regulating cell cycle progression. We also found that RB was co-localized with C-terminal binding protein interacting protein CtIP (also named as RBBP8), which is one of the initiation proteins contributing to DNA end resection. We used a DNA topoisomerase inhibitor camptothecin (CPT) to induce DSBs in human U2OS cells. Cells with RB knocked-down showed higher sensitivity to CPT treatment. In CPT treated cells, less Replication Protein A (RPA) and native BrdU foci could be detected in RB knocked-down cells, which imply a RB function in controlling DNA end resection. In addition, in RB knocked-down cells, less CtIP foci was detected in nuclei, while the total CtIP expression level was not affected. We also found that there was less CtIP phosphorylation on Thr847 in RB knocked-down cells. Thr847 on CtIP has been reported to be phosphorylated by CDK. Therefore, we hypothesize RB regulates the phosphorylation of CtIP Thr847 and the functions of CtIP to control DNA end resection and DSB repair pathways. To further evaluate the roles of the interaction between RB and CtIP in DSB repair, we disrupted physical binding between RB and CtIP by mutating the reported RB binding site glutamic acid on position 157 to lysine (E157K). After an attempt to knock out the endogenous CtIP by CRISPR technology, recombinant wild type and mutated GFP-CtIP were overexpressed in U2OS cells under the regulation of doxycycline. DNA end resection was also measured in these cells by quantification of RPA foci. However, as CtIP is an essential protein to the cell viability, it has been reported that at least one wild type CtIP allele is needed to support the cell survival. Indeed, it has been found that there are three copies of CtIP alleles in U2OS cells. So we could not fully knock out the endogenous CtIP by CRISPR. Based on these results, less RPA foci were shown in mutant CtIP E157K cells, which implies that physical binding between RB and CtIP could be important for DSB repair pathway choices and DNA end resection.PARP1 has been reported to be an important protein at the early stage of DNA end resection, which mainly contributes to the MMEJ repair pathway. As RB knocked-down cells showed lower HR and NHEJ efficiencies, while the MMEJ efficiency was elevated, we hypothesized that RB knocked-down cells would be more sensitive to the CPT and PARP1 inhibitor co-treatment than the single CPT treatment. Our results demonstrated a synthetic lethality in RB knocked-down cells in response to PARP inhibitor and CPT. These results could help us to understand how RB deficient cancers response to chemotherapy and could be useful for improving treatment in RB deficient cancers.Besides the U2OS cells, during my PhD study, two retinoblastoma primary retinoblastoma patients’ cell lines and also the retinoblastoma Y79 cell line were studied. We detected CRX, which is usually expressed in cone cells, to prove that Y79 cells and retinoblastoma primary cells possessed some cone cell properties. In addition, interestingly, one of the primary retinoblastoma cells also showed RB signal in both immunofluorescence and western blot. In one retinoblastoma patient, the enucleated tumour could be cultured as both floating cells and adherent cells. RB expression and CRX immunofluorescence could be detected in both of these cells. We also attempted to transfect a RB expressing plasmid into Y79 cells, RPE cells and retinoblastoma patient cells. However, only one retinoblastoma patient cells were transfected successfully. These primary retinoblastoma cells could be employed to further explore the RB functions in DSB repair in the future. In conclusion, my PhD study investigated he relationship of retinoblastoma and genome instability. My studies could help to improve the potential therapy for retinoblastoma. Our studies also help us to understand the mechanism of RB in response to DNA damages, which could contribute to the disease management of retinoblastoma and other RB deficient cancers.Our studies lead to conclusions that RB deficient cancer depends on MMEJ repair DSBs. The mechanism of RB function on DSBs repair pathways choice is related to RB regulating CtIP mediated DNA end resection. Interaction of RB and CtIP contributes to DNA end resection. Specific targeting MMEJ by PARP inhibitor could be used to improve clinic management of retinoblastoma patients.視網膜母細胞瘤蛋白（RB） 是一種腫瘤抑制因數，因其在調節轉錄和細胞增殖中的作用聞名。它由RB1基因編碼。雙等位基因RB1突變將導致RB 蛋白失活。RB首先在兒童眼癌視網膜母細胞瘤中發現。RB蛋白失活也可在其他癌症（例如肺癌， 乳腺癌等）中發現。RB在人細胞中的多種作用已被發現，包括調節細胞遷移，防止線粒體缺陷和調節多種信號通路。最近的研究確定了RB突變的功能還將導致染色體不穩定和非整倍性，發現RB位於DNA 雙鏈斷裂（DSB）上，它與γH2AX共定位。γH2AX是在DSB的重要標誌物，它是組蛋白H2A絲氨酸139的磷酸化蛋白。在我的博士研究中，我發現了人骨癌細胞U2OS中RB 在DNA DSB剪切中的功能， 這是DSB修復途徑中的重要的一步。我的實驗結果表明RB 在促進DSB修復過程中促進DSB末端剪切中起了重要作用。此外，我發現RB 可以促進同源重組（HR）和經典非同源末端連結（NHEJ）通路，這是DSB 主要的修復途徑。相反，RB敲低的細胞顯示出高水準的為同源末端連結（MMEJ），這是另一種涉及微小DNA 末端切除的DSB修復途徑。我的結果表明，RB在調節DNA DSB修復途徑中的作用與其在調節細胞週期進程中的作用無關。我還發現RB 與C末端結合蛋白相互作用蛋白CtIP(也稱為RB第8結合蛋白RBBP8)共定位，後者是導致DNA末端剪切的重要蛋白之一。我使用了一種DNA拓撲異構酶抑制劑喜樹堿（CPT）來誘導人U2OS細胞中的DSB。RB 基因敲低的細胞對CPT顯示更高的敏感性。在經CPT處理的細胞中，在RB敲低的細胞中可檢測到較少的複製蛋白A（RPA）和BrdU蛋白集合灶。這意味著RB在控制DNA末端切除中具有功能。另外，在RB敲低的細胞中，細胞核中檢測到減少的CtIP集合灶，而CtIP的總體表達水準不受影響。我還發現在RB 敲低的細胞中CtIP 蘇氨酸847 （Thr847） 位置的磷酸化蛋白減少。據報導，CtIP Thr847被CDK 磷酸化。因此，我假設RB調節CtIP Thr847的磷酸化和CtIP的功能，以控制DNA 末端切除和DSB修復途徑。為了更好的檢測DNA末端剪切的程度，單分子切除分析（SMART）用於測量DNA剪切的長度。DSB 通過在RB基因敲低的U20S細胞中由電離輻射導致DSB。不幸的是，SMART結果並不支持RB基因敲低的細胞中出現較短的DNA剪切鏈。為了進一步評估RB 和CtIP之間的相互作用在DSB修復中的作用，我通過建立CtIP蛋白157位點谷氨酸突變為賴氨酸（E157K）細胞，這個位點的突變會破壞RB與CtIP 的物理結合。嘗試通過CRISPR技術敲出內源性CtIP後，在強力黴素的調控下，重組的野生型和突變的GFP-CtIP在U2OS細胞中得到表達。然後將這些細胞用於測量DSB相關的參數。通過使用RPA集合灶的測量來評估DNA末端剪切的情況。然而，CtIP是細胞存活的必須蛋白。據報導，至少需要一條野生型CtIP等位基因來支援細胞存活。實際上，已經發現在U2OS細胞中存在三條CtIP等位基因。因此無法使用CRISPR 技術完全敲除內源性CtIP。根據這些結果，在突變的CtIP E157K 細胞中顯示較少的RPA集合灶，表明RB 與CtIP之間的物理結合對於DSB修復途徑的選擇和DNA末端剪切有重要作用。據報導，PARP1(聚腺苷酸二磷酸核糖基聚合酶1)在DNA末端剪切的早期是一種重要的蛋白質，主要有助於MMEJ修復途徑。由於RB敲低的細胞顯示出較低的HR和NHEJ效率，而提高了MMEJ效率用於修復DSB，我推測RB 敲低的細胞對CPT和PARP1抑制劑的聯合治療比單一CPT治療更敏感。我的結果表明，RB敲低細胞對PARP抑制劑和CPT聯合治療反應更明顯。這些研究發現可以幫助我們瞭解RB缺乏型癌症對化療的反應，並幫助改善RB 缺乏型癌症的治療。除了U2OS細胞外， 在我的博士研究期間，我還研究了兩個視網膜母細胞瘤患者的原代細胞以及視網膜母細胞瘤Y79細胞系。我檢測到在視網膜視錐細胞中表達的一種蛋白CRX，證明了Y79細胞核視網膜母細胞瘤原代細胞來源於視錐細胞。另外，有趣的是，原代視網膜母細胞瘤細胞之一在免疫螢光和蛋白質印記中也顯示出RB信號。另一名視網膜母細胞瘤患者，也可檢測到低表達的RB信號。我還試圖將表達RB的質粒轉染到Y79 和原代視網膜母細胞瘤細胞。這些原代視網膜母細胞瘤細胞可用於將來進一步探索RB在DSB修復中的功能。總之，我的博士研究專注于視網膜母細胞瘤與基因不穩定的關係。我的研究可能有助於改善視網膜母細胞瘤的潛在治療方法。我的研究還幫助我們瞭解RB對於DNA損傷的反應機制，這些都有助於視網膜母細胞瘤和其他RB缺乏型癌症的臨床管理。RB 缺乏型癌細胞依賴MMEJ修復DSBs，RB 功能對DSB是修復途徑選擇的機制與RB 調控CtIP介導的DNA末端切除有關。RB和CtIP的相互作用有助於DNA末端切除。PARP抑制劑作為特異性靶向阻斷MMEJ，可用於改善視網膜母細胞瘤患者的臨床管理。Jiang, Yuning.Thesis Ph.D. Chinese University of Hong Kong 2020.Includes bibliographical references (leaves 168-177).Abstracts also in Chinese.Title from PDF title page (viewed on 29, September 2021).Jiang, Yuning
Enterprise architecture modeling for cybersecurity analysis in critical infrastructures — A systematic literature review
No full textAs digital landscapes become increasingly complex, safeguarding sensitive information and systems against cyber threats has become a paramount concern for organizations. This paper provides a comprehensive review of how enterprise architecture modeling is used in the context of cybersecurity assessment, particularly focusing on critical infrastructures. The use of enterprise architecture models for cybersecurity is motivated by the main purpose of enterprise architecture, namely to represent and manage business and IT assets and their interdependence. While enterprise architecture modeling originally served to assess Business/IT alignment, they are increasingly used to assess the cybersecurity of the enterprise. The research questions explored include the types of enterprise architecture models used for cybersecurity assessment, how security aspects are incorporated into these models, the theoretical frameworks and reference theories applied, the research methods used for evaluation, and the strengths and limitations of these models in supporting cybersecurity assessment. This review encompasses research papers published before 2024, focusing on high-quality research from peer-reviewed journals and reputable conferences, thereby providing a structured and comprehensive overview of the current state of research in this domain.CC BY-NC 4.0Corresponding author: Yuning JiangE-mail addresses: [email protected]</p
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