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1. DNA Methylation signatures underpinning blood neutrophil to lymphocyte ratio during first week of human life

Author: David Martino, Nina Kresoje, Nelly Amenyogbe, Rym Ben-Othman, Bing Cai, Mandy Lo, Olubukola Idoko, Oludare A. Odumade, Reza Falsafi, Travis M. Blimkie, Andy An, Casey P. Shannon, Sebastiano Montante, Bhavjinder K. Dhillon, Joann Diray-Arce, Al Ozonoff, Kinga K. Smolen, Ryan R. Brinkman, Kerry McEnaney, Asimenia Angelidou, Peter Richmond, Scott J. Tebbutt, the EPIC-HIPC consortium, Beate Kampmann, Ofer Levy, Robert E. W. Hancock, Amy H. Y. Lee, and Tobias R. Kollmann
Subjects: Science
Abstract: Abstract Understanding of newborn immune ontogeny in the first week of life will enable age-appropriate strategies for safeguarding vulnerable newborns against infectious diseases. Here we conducted an observational study exploring the immunological profile of infants longitudinally throughout their first week of life. Our Expanded Program on Immunization - Human Immunology Project Consortium (EPIC-HIPC) studies the epigenetic regulation of systemic immunity using small volumes of peripheral blood samples collected from West African neonates on days of life (DOL) 0, 1, 3, and 7. Genome-wide DNA methylation and single nucleotide polymorphism markers are examined alongside matched transcriptomic and flow cytometric data. Integrative analysis reveals that a core network of transcription factors mediates dynamic shifts in neutrophil-to-lymphocyte ratios (NLR), which are underpinned by cell-type specific methylation patterns in the two cell types. Genetic variants are associated with lower NLRs at birth, and healthy newborns with lower NLRs at birth are more likely to subsequently develop sepsis. These findings provide valuable insights into the early-life determinants of immune system development.
Published: 2024
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2. Helping Mentors Address Scientific Communication in STEM Research Training Helps Their Mentees Stay the Course

Author: C. Cameron, H. Y. Lee, C. B. Anderson, E. K. Dahlstrom, and S. Chang
Abstract: Scientific communication (SC) has important social-cognitive, behavioral, and career-related benefits for emerging researchers, but both mentors and mentees find development of SC skills challenging. Whether training mentors to effectively mentor development of SC skills could have a meaningful impact on mentees was not clear. The Scientific Communication Advances Research Excellence (SCOARE) project has conducted faculty training workshops in techniques for mentoring SC skills since 2018. To study indirect workshop effects of mentors' attendance at the SCOARE workshop on their matched PhD and postdoctoral mentees (N = 477), we surveyed mentees before and 6 months after their mentors attended and measured their social-psychological and behavioral outcomes. To examine the effectiveness of the workshop and to explore whether workshop effects vary based on mentee demographic characteristics, including home language variety (speaker of standardized English [STE], non-standardized English [NSTE], or another language [L2]), we conducted multilevel models. After adjusting baseline scores, mentees of mentors who attended SCOARE workshops (W +) were more engaged in speaking activities ([beta] =0 .30, p = 0.016), had higher science identity ([beta] = 0.20, p = 0.048), and were less likely to reconsider their career due to SC skills ([beta] = -- 0.39, p = 0.004) than mentees in the W-- group. Across demographic groups, mentees of mentors who attended SCOARE workshops showed similar improvements in SC outcomes. Postdoctoral mentees, compared to doctoral mentees, had higher science identity and lower intention to pursue a non-research-intensive career. Comparing mentees of the 3 categories of home language variety, both the NSTE and L2 groups, compared to the STE group, were more likely to reconsider their careers due to SC skills and had a higher intention to pursue non-research-intensive careers both at baseline and post-workshop, suggesting the possibility of language background as a barrier to mentee career progression. Mentor training for SC skill development can improve social-psychological and behavioral outcomes for mentees, including science identity, frequency of speaking, and reconsideration of research careers due to concerns about SC.
Published: 2024
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3. Transportation to School and Academic Outcomes: A Systematic Review

Author: Laura M. Hopson, A. D. Lidbe, M. S. Jackson, E. Adanu, X. Li, P. Penmetsa, H. Y. Lee, A. Anderson, C. Obuya, and G. Abura-Meerdink
Abstract: School transportation may have important implications for academic success, but few studies examine how these variables are related. This systematic review is the first that synthesizes research linking school transportation with academic outcomes. Using the PRISMA framework, the authors conducted a literature search across multiple data sources and screened articles for the following eligibility criteria: 1) Design is quantitative or mixed methods; 2) Sample consists of primary or secondary school students; 3) Variables include school transportation and academic outcomes. Two reviewers independently screened each study for inclusion criteria. Two reviewers also independently rated each study on methodological quality in five dimensions using the Mixed Methods Appraisal Tool (MMAT). Throughout the process, reviewers consulted to resolve any discrepancies between ratings. The search revealed 249 abstracts that were screened for inclusion criteria. This resulted in 61 relevant articles after duplicates were removed. After screening, reviewers determined that 26 studies met inclusion criteria. Most took place in the United States, although studies were also conducted in Canada, Croatia, England, Nepal, Pakistan, Portugal, South Africa, and Spain. Thirteen studies met all MMAT methodological quality standards. Longer travel times and transportation challenges were associated with adverse academic outcomes except when they provided access to higher-quality schools. School bus transportation had a mixed relationship with academic outcomes. The authors conclude that research points to the importance of transportation as it relates to academic success, especially for students of color and those from low-income households.
Published: 2024
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4. Deciphering sepsis: transforming diagnosis and treatment through systems immunology

Author: Robert E. W. Hancock, Andy An, Claudia C. dos Santos, and Amy H. Y. Lee
Subjects: sepsis, systems immunology, diagnostics, endotypes, RNA-Seq, multiomics, Science
Abstract: Sepsis is an abnormal, life-threatening response to infection that leads to (multi-)organ dysfunction and failure. It causes ~20% of deaths worldwide each year, and most deaths related to severe COVID-19 share various molecular features with sepsis. Current treatment approaches (antimicrobials and supportive care) do not address the complexity of sepsis or its mechanistic heterogeneity between and within patients over time. Systems immunology methods, including multiomics (notably RNA sequencing transcriptomics), machine learning, and network biology analysis, have the potential to transform the management paradigm toward precision approaches. Immune dysfunctions evident very early in sepsis drive the development of novel diagnostic gene expression signatures (e.g., cellular reprogramming) that could inform early therapy. Sepsis patients can now be categorized into “endotypes” based on unique immune dysfunction mechanisms corresponding to varying severity and mortality rates, raising the prospect of endotype-specific diagnostics and patient-specific immune-directed therapy. Longitudinal within-patient analyses can also reveal mechanisms (including epigenetics) that drive differential sepsis trajectories over time, enabling the prospect of disease stage-specific therapy during and after hospitalization, including for post-sepsis and long COVID syndromes. Achieving this transformation will require addressing barriers to systems immunology research, including its cost and resource-intensiveness, the relatively low volume of available data, and lack of suitable animal models; it will also require a change in the mindset of healthcare providers toward precision approaches. This should be prioritized in multistakeholder collaborations involving research communities, healthcare providers/systems, patients, and governments to reduce the current high disease burden from sepsis and to mitigate against future pandemics.
Published: 2025
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5. Metropolitan Planning Organizations’ Uses of and Needs for Big Data

Author: Ekin Ugurel, Xinhua Wu, Ryan Wang, Brian H. Y. Lee, and Cynthia Chen
Subjects: Transportation and communications, HE1-9990, Urban groups. The city. Urban sociology, HT101-395
Abstract: Big data products offer a new paradigm to understand and analyze human mobility patterns, a primary interest of long-range transportation planners. However, it remains unclear how widely these datasets are utilized by planners and to what extent they influence decision-making. We present the perspectives of more than 50 planners from MPOs across the United States. While we found a range of use cases, there was also a tendency to focus on a narrow set of applications. *Transparency*, *regulation*, and *legitimacy* emerged as the primary factors influencing adoption decisions.
Published: 2024
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6. Nonproportionality of NaI(Tl) scintillation detector for dark matter search experiments

Author: COSINE-100 Collaboration, S. M. Lee, G. Adhikari, N. Carlin, J. Y. Cho, J. J. Choi, S. Choi, A. C. Ezeribe, L. E. França, C. Ha, I. S. Hahn, S. J. Hollick, E. J. Jeon, H. W. Joo, W. G. Kang, M. Kauer, B. H. Kim, H. J. Kim, J. Kim, K. W. Kim, S. H. Kim, S. K. Kim, S. W. Kim, W. K. Kim, Y. D. Kim, Y. H. Kim, Y. J. Ko, D. H. Lee, E. K. Lee, H. Lee, H. S. Lee, H. Y. Lee, I. S. Lee, J. Lee, J. Y. Lee, M. H. Lee, S. H. Lee, Y. J. Lee, D. S. Leonard, N. T. Luan, B. B. Manzato, R. H. Maruyama, R. J. Neal, J. A. Nikkel, S. L. Olsen, B. J. Park, H. K. Park, H. S. Park, J. C. Park, K. S. Park, S. D. Park, R. L. C. Pitta, H. Prihtiadi, S. J. Ra, C. Rott, K. A. Shin, D. F. F. S. Cavalcante, A. Scarff, M. K. Son, N. J. C. Spooner, L. T. Truc, L. Yang, and G. H. Yu
Subjects: Astrophysics, QB460-466, Nuclear and particle physics. Atomic energy. Radioactivity, QC770-798
Abstract: Abstract We present a comprehensive study of the nonproportionality of NaI(Tl) scintillation detectors within the context of dark matter search experiments. Our investigation, which integrates COSINE-100 data with supplementary $$\gamma $$ γ spectroscopy, measures light yields across diverse energy levels from full-energy $$\gamma $$ γ peaks produced by the decays of various isotopes. These $$\gamma $$ γ peaks of interest were produced by decays supported by both long and short-lived isotopes. Analyzing peaks from decays supported only by short-lived isotopes presented a unique challenge due to their limited statistics and overlapping energies, which was overcome by long-term data collection and a time-dependent analysis. A key achievement is the direct measurement of the 0.87 keV light yield, resulting from the cascade following electron capture decay of $$\mathrm {^{22}Na}$$ 22 Na from internal contamination. This measurement, previously accessible only indirectly, deepens our understanding of NaI(Tl) scintillator behavior in the region of interest for dark matter searches. This study holds substantial implications for background modeling and the interpretation of dark matter signals in NaI(Tl) experiments.
Published: 2024
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7. Pseudomonas aeruginosa in chronic lung disease: untangling the dysregulated host immune response

Author: Rhea Nickerson, Christina S. Thornton, Brent Johnston, Amy H. Y. Lee, and Zhenyu Cheng
Subjects: Pseudomonas aeruginosa, chronic lung disease, inflammation, neutrophils, innate immune response, adaptive immune response, Immunologic diseases. Allergy, RC581-607
Abstract: Pseudomonas aeruginosa is a highly adaptable opportunistic pathogen capable of exploiting barriers and immune defects to cause chronic lung infections in conditions such as cystic fibrosis. In these contexts, host immune responses are ineffective at clearing persistent bacterial infection, instead driving a cycle of inflammatory lung damage. This review outlines key components of the host immune response to chronic P. aeruginosa infection within the lung, beginning with initial pathogen recognition, followed by a robust yet maladaptive innate immune response, and an ineffective adaptive immune response that propagates lung damage while permitting bacterial persistence. Untangling the interplay between host immunity and chronic P. aeruginosa infection will allow for the development and refinement of strategies to modulate immune-associated lung damage and potentiate the immune system to combat chronic infection more effectively.
Published: 2024
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8. Detection rates and factors affecting thereof in endometrial hyperplasia, endometrial carcinoma, and cervical glandular lesions on cervical smear

Author: Joanna K. M. Ng, Bryan H. C. Cheung, Dennis H. Y. Lee, Joshua J. X. Li, Philip P. C. Ip, Jacqueline H. S. Lee, Carol S. Y. Yeung, and Mei‐Yung Yu
Subjects: cervical adenocarcinoma, cervical smear, endometrial carcinoma, endometrial hyperplasia, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract Introduction Endometrial lesions are morphologically diverse and uncommon on cervical smears, with its detection rate and associated diagnostic categories uncharacterized. In this study, cervical smears matched to histologically proven endometrial hyperplasias and carcinomas were reviewed and compared with cervical in‐situ‐carcinomas/carcinomas, aiming to detail the diagnostic performance of cervical smears for upper tract and glandular lesions. Methods Pathology reports of cervical smears, hysterectomies, endometrial and cervical biopsies from 1995 to 2021 were retrieved. Diagnoses of cervical smears were matched to endometrial hyperplasias and carcinomas, or cervical carcinomas and reviewed. Results Totally 832 cervical smears (272 cervical carcinomas, 312 endometrial carcinomas, and 248 hyperplasias) were included. Considering all cytologic glandular diagnosis as positive, the detection rate of cervical adenocarcinoma‐in‐situ was the highest (64.3%), followed by cervical adenocarcinoma (63.8%), endometrial carcinoma (31.7%), and hyperplasia (with atypia–8.5%; without atypia–2.3%) (p
Published: 2023
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9. The Evolution of Anorexia Nervosa in Singapore: A 30-year Demographic Analysis

Author: H. Y. Lee and V. K. H. Wong
Subjects: Psychiatry, RC435-571
Abstract: Introduction New prevalence and time trend data from various Asian countries show that Eating Disorders (ED) are increasingly common in Asia. (Youl-Ri Kim. Int J Eat Disord. Dec 2020). A recent study estimating the prevalence of ED in Singapore found an alarming 6.2% screened positive for a clinical ED diagnosis, 19.5% were screened to be at high risk, and estimated the point prevalence of Anorexia Nervosa (AN) to be 0.9%. (Chua SN et al. Int J Eat Disord. Jan 2021). The ED unit in Singapore General Hospital (SGH) was set up in 2003 as a National Treatment Programme for patients with ED. Two local studies have been published to date on the demographics and clinical profile of patients with AN. The first study examined 126 patients from 1994 – 2002 (HY Lee et al. Singapore Med J 2005; 46(6): 275-281). The second study reported on 271 cases from our SGH ED unit from 2003-2010 (Kuek et al. SIngapore Med J 2015; 56(6): 324-328). There have been no further studies in the last decade. Objectives 1. Study the demographics and clinical profile of patients who presented with AN to our ED unit from 2011-2022 2. Compare our data with the 2 previous studies and examine for any changes and trends in the past 30 years. Methods We conducted a review of the ED unit new case registry at SGH from 2011-2022. A total of 910 patients were diagnosed with AN at presentation. The data was analysed with approval from the hospital instituitional review board. Results A total of 910 cases presented with AN over 12 years. Comparing with the 2 previous studies, the number of new cases each year has continued to increase from
Published: 2024
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10. A New Ramp Stress Reliability Assessment on Pulse Energy Based OTS Switching Operation.

Author: P. C. Chang, P. J. Liao, C. H. Wu, Y. C. Chang, D. H. Hou, Elia Ambrosi, H. Y. Lee, J. H. Lee, and X. Y. Bao
Published: 2023
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11. P-type SnO Semiconductor Transistor and Application.

Author: C. C. Wang, C. C. Kuo, C. H. Wu, A. Lu, H. Y. Lee, C. F. Hsu, P. J. Tzeng, T. Y. Lee, F. R. Hou, M. H. Chang, S. C. Lai, K. Goto, Shimeng Yu, C. I. Wu, C. T. Lin, Y. M. Lin, and X. Y. Bao
Published: 2024
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12. GRANODIORITES OF OLEKMINSKY COMPLEX OF THE EASTERN TRANSBAIKALIA: U-Pb LA-ICP-MS ZIRCONS GEOCHRONOLOGY AND AGE POSITION OF COMPLEX

Author: S. I. Dril, V. P. Kovach, А. В. Kotov, K.-L. Wang, А. М. Larin, Y. Iizuka, and H.-Y. Lee
Subjects: mongol-okhotsk orogenic belt, zircon la-icp-ms u-pb geochronological data, western-stanovoy terrane, olekminsky intrusive complex, Science
Abstract: The palingenic calc-alkaline granitoid massifs of the Olekminsky complex form a magmatic belt stretching within the Western-Stanovoy terrane in the northeastern direction for more than 700 km. New U-Pb LA-ICP-MS dates for zircons from the granodiorites of the Marekta-Bereinsky massif of the Olekminsky complex and the granodiorites of the Yamninsky massif of the Krestovsky complex were obtained, amounting to 371±4 Ma and 364±5 Ma, respectively. These geochronological data are well consistent with the 355–358 Ma ones, therefore suggesting the Late Carboniferous age of quartz-diorite-granodiorite-granite rocks of the Olekminsky complex. However, these dates are not correlated with the existing legends of geological maps covering the area of the Western-Stanovoy structural-formation zone or the Western-Stanovoy terrane, as the intrusive formations of the Olekminsky complex are dated as the Early Paleozoic. In addition, new geochronological data call into question distinguishing of a separate Early Paleozoic Krestovsky granitoid complex.
Published: 2024
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13. Incentives to Persevere.

Author: Elif Incekara-Hafalir, Grace H. Y. Lee, Audrey K. L. Siah, and Erte Xiao
Published: 2023
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14. Predicting severity in COVID-19 disease using sepsis blood gene expression signatures

Author: Arjun Baghela, Andy An, Peter Zhang, Erica Acton, Jeff Gauthier, Elsa Brunet-Ratnasingham, Travis Blimkie, Gabriela Cohen Freue, Daniel Kaufmann, Amy H. Y. Lee, Roger C. Levesque, and Robert E. W. Hancock
Subjects: Medicine, Science
Abstract: Abstract Severely-afflicted COVID-19 patients can exhibit disease manifestations representative of sepsis, including acute respiratory distress syndrome and multiple organ failure. We hypothesized that diagnostic tools used in managing all-cause sepsis, such as clinical criteria, biomarkers, and gene expression signatures, should extend to COVID-19 patients. Here we analyzed the whole blood transcriptome of 124 early (1–5 days post-hospital admission) and late (6–20 days post-admission) sampled patients with confirmed COVID-19 infections from hospitals in Quebec, Canada. Mechanisms associated with COVID-19 severity were identified between severity groups (ranging from mild disease to the requirement for mechanical ventilation and mortality), and established sepsis signatures were assessed for dysregulation. Specifically, gene expression signatures representing pathophysiological events, namely cellular reprogramming, organ dysfunction, and mortality, were significantly enriched and predictive of severity and lethality in COVID-19 patients. Mechanistic endotypes reflective of distinct sepsis aetiologies and therapeutic opportunities were also identified in subsets of patients, enabling prediction of potentially-effective repurposed drugs. The expression of sepsis gene expression signatures in severely-afflicted COVID-19 patients indicates that these patients should be classified as having severe sepsis. Accordingly, in severe COVID-19 patients, these signatures should be strongly considered for the mechanistic characterization, diagnosis, and guidance of treatment using repurposed drugs.
Published: 2023
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15. Post-COVID symptoms are associated with endotypes reflecting poor inflammatory and hemostatic modulation

Author: Andy Yi An, Arjun Baghela, Peter G. Y. Zhang, Travis M. Blimkie, Jeff Gauthier, Daniel Elias Kaufmann, Erica Acton, Amy H. Y. Lee, Roger C. Levesque, and Robert E. W. Hancock
Subjects: long COVID, COVID-19, endotypes, gene expression, personalized medicine, Immunologic diseases. Allergy, RC581-607
Abstract: IntroductionPersistent symptoms after COVID-19 infection (“long COVID”) negatively affects almost half of COVID-19 survivors. Despite its prevalence, its pathophysiology is poorly understood, with multiple host systems likely affected. Here, we followed patients from hospital to discharge and used a systems-biology approach to identify mechanisms of long COVID.MethodsRNA-seq was performed on whole blood collected early in hospital and 4-12 weeks after discharge from 24 adult COVID-19 patients (10 reported post-COVID symptoms after discharge). Differential gene expression analysis, pathway enrichment, and machine learning methods were used to identify underlying mechanisms for post-COVID symptom development.ResultsCompared to patients with post-COVID symptoms, patients without post-COVID symptoms had larger temporal gene expression changes associated with downregulation of inflammatory and coagulation genes over time. Patients could also be separated into three patient endotypes with differing mechanistic trajectories, which was validated in another published patient cohort. The “Resolved” endotype (lowest rate of post-COVID symptoms) had robust inflammatory and hemostatic responses in hospital that resolved after discharge. Conversely, the inflammatory/hemostatic responses of “Suppressive” and “Unresolved” endotypes (higher rates of patients with post-COVID symptoms) were persistently dampened and activated, respectively. These endotypes were accurately defined by specific blood gene expression signatures (6-7 genes) for potential clinical stratification.DiscussionThis study allowed analysis of long COVID whole blood transcriptomics trajectories while accounting for the issue of patient heterogeneity. Two of the three identified and externally validated endotypes (“Unresolved” and “Suppressive”) were associated with higher rates of post-COVID symptoms and either persistently activated or suppressed inflammation and coagulation processes. Gene biomarkers in blood could potentially be used clinically to stratify patients into different endotypes, paving the way for personalized long COVID treatment.
Published: 2023
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16. Advances in New Zealand's Tephrochronostratigraphy Using Marine Drill Sites: The Neogene

Author: K. Pank, S. Kutterolf, J. L. Hopkins, K.‐L. Wang, H.‐Y. Lee, and A. K. Schmitt
Subjects: marine tephrochronostratigraphy, geochemical fingerprinting, correlations of marine tephras between individual drill sites, IODP, ODP and DSDP drill sites, neogene eruption record of New Zealand, Geophysics. Cosmic physics, QC801-809, Geology, QE1-996.5
Abstract: Abstract Three volcanic arcs have been the source of New Zealand's volcanic activity since the Neogene: Northland arc, Coromandel Volcanic Zone (CVZ) and Taupō Volcanic Zone (TVZ). The eruption chronology for the Quaternary, sourced by the TVZ, is well studied and established, whereas the volcanic evolution of the precursor arc systems, like the CVZ (central activity c. 18 to 2 Ma), is poorly known due to limited accessibility to, or identification of, onshore volcanic deposits and their sources. Here, we investigate the marine tephra record of the Neogene, mostly sourced by the CVZ, of cores from IODP Exp. 375 (Sites U1520 and U1526), ODP Leg 181 (Sites 1123, 1124 and 1125), IODP Leg 329 (Site U1371) and DSDP Leg 90 (Site 594) offshore of New Zealand. In total, we identify 306 primary tephra layers in the marine sediments. Multi‐approach age models (e.g. biostratigraphy, zircon ages) are used in combination with geochemical fingerprinting (major and trace element compositions) and the stratigraphic context of each marine tephra layer to establish 168 tie‐lines between marine tephra layers from different holes and sites. Following this approach, we identify 208 explosive volcanic events in the Neogene between c. 17.5 and 2.6 Ma. This is the first comprehensive study of New Zealand's Neogene explosive volcanism established from tephrochronostratigraphic studies, which reveals continuous volcanic activity between c. 12 and 2.6 Ma with an abrupt compositional change at c. 4.5 Ma, potentially associated with the transition from CVZ to TVZ.
Published: 2023
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17. Salt and surfactant coated filters with antiviral properties and low pressure drop for prospective SARS-CoV2 applications

Author: Milad Ebadi, Claire McCague, Ophelia Vallee, Patrick K. Taylor, Amy H. Y. Lee, and Majid Bahrami
Subjects: Medicine, Science
Abstract: Abstract The COVID-19 pandemic motivated research on antiviral filtration used in personal protective equipment and HVAC systems. In this research, three coating compositions of NaCl, Tween 20 surfactant, and NaCl-Tween 20 were examined on polypropylene spun-bond filters. The pressure drop, coverage, and crystal size of the coating methods and compositions were measured. Also, in vitro plaque assays of the Phi6 Bacteriophage on Pseudomonas syringae as a simulation of an enveloped respiratory virus was performed to investigate the antiviral properties of the coating. NaCl and NaCl-Tween 20 increased the pressure drop in the range of 40–50 Pa for a loading of 5 mg/cm2. Tween 20 has shown an impact on the pressure drop as low as 10 Pa and made the filter surface more hydrophilic which kept the virus droplets on the surface. The NaCl-Tween 20 coated samples could inactivate 108 plaque forming units (PFU) of virus in two hours of incubation. Tween 20 coated filters with loading as low as 0.2 mg/cm2 reduced the activity of 108 PFU of virus from 109 to 102 PFU/mL after 2 h of incubation. NaCl-coated samples with a salt loading of 15 mg/cm2 could not have antiviral properties higher than reducing the viral activity from 109 to 105 PFU/mL in 4 h of incubation.
Published: 2022
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18. Identification of Ndfip1 as a novel negative regulator for spatial memory formation associated with increased ubiquitination of Beclin 1 and PTEN

Author: Wei-Lun Hsu, Yun-Li Ma, Yan-Chu Chen, Yen-Chen Liu, Kuang-Min Cheng, and Eminy H. Y. Lee
Subjects: Medicine, Science
Abstract: Long-term memory formation requires de novo RNA and protein synthesis. By using the differential display-polymerase chain reaction strategy, we have presently identified the Nedd4 family interacting protein 1 (Ndfip1) cDNA fragment that is differentially expressed between the slow learners and the fast learners from the water maze learning task in rats. Further, the fast learners show decreased Ndfip1 mRNA and protein expression levels than the slow learners. Spatial training similarly decreases the Ndfip1 mRNA and protein expression levels. Conversely, the Ndfip1 conditional heterozygous (cHet) mice show enhanced spatial memory performance compared to the Ndfip1flox/WT control mice. Result from co-immunoprecipitation experiment indicates that spatial training decreases the association between Ndfip1 and the E3 ubiquitin ligase Nedd4 (Nedd4-1), and we have shown that both Beclin 1 and PTEN are endogenous ubiquitination targets of Nedd4 in the hippocampus. Further, spatial training decreases endogenous Beclin 1 and PTEN ubiquitination, and increases Beclin 1 and PTEN expression in the hippocampus. On the other hand, the Becn1 conditional knockout (cKO) mice and the Pten cKO mice both show impaired spatial learning and memory performance. Moreover, the expression level of Beclin 1 and PTEN is higher in the Ndfip1 cHet mice compared with the Ndfip1flox/WT control mice. Here, we have identified Ndfip1 as a candidate novel negative regulation for spatial memory formation and this is associated with increased ubiquitination of Beclin 1 and PTEN in the hippocampus.
Published: 2023

19. Background modeling for dark matter search with 1.7 years of COSINE-100 data

Author: G. Adhikari, E. Barbosa de Souza, N. Carlin, J. J. Choi, S. Choi, M. Djamal, A. C. Ezeribe, L. E. França, C. Ha, I. S. Hahn, E. J. Jeon, J. H. Jo, H. W. Joo, W. G. Kang, M. Kauer, H. Kim, H. J. Kim, K. W. Kim, S. H. Kim, S. K. Kim, W. K. Kim, Y. D. Kim, Y. H. Kim, Y. J. Ko, E. K. Lee, H. Lee, H. S. Lee, H. Y. Lee, I. S. Lee, J. Lee, J. Y. Lee, M. H. Lee, S. H. Lee, S. M. Lee, D. S. Leonard, W. A. Lynch, B. B. Manzato, R. H. Maruyama, R. J. Neal, S. L. Olsen, B. J. Park, H. K. Park, H. S. Park, K. S. Park, R. L. C. Pitta, H. Prihtiadi, S. J. Ra, C. Rott, K. A. Shin, A. Scarff, N. J. C. Spooner, W. G. Thompson, L. Yang, G. H. Yu, and COSINE-100 Collaboration
Subjects: Astrophysics, QB460-466, Nuclear and particle physics. Atomic energy. Radioactivity, QC770-798
Abstract: Abstract We present a background model for dark matter searches using an array of NaI(Tl) crystals in the COSINE-100 experiment that is located in the Yangyang underground laboratory. The model includes background contributions from both internal and external sources, including cosmogenic radionuclides and surface $$^{210}$$ 210 Pb contamination. To build the model in the low energy region, with a threshold of 1 keV, we used a depth profile of $$^{210}$$ 210 Pb contamination in the surface of the NaI(Tl) crystals determined in a comparison between measured and simulated spectra. We also considered the effect of the energy scale errors propagated from the statistical uncertainties and the nonlinear detector response at low energies. The 1.7 years COSINE-100 data taken between October 21, 2016 and July 18, 2018 were used for this analysis. Our Monte Carlo simulation provides a non-Gaussian peak around 50 keV originating from beta decays of bulk $$^{210}$$ 210 Pb in a good agreement with the measured background. This model estimates that the activities of bulk $$^{210}$$ 210 Pb and $$^{3}$$ 3 H are dominating the background rate that amounts to an average level of $$2.85\pm 0.15$$ 2.85 ± 0.15 counts/day/keV/kg in the energy region of (1–6) keV, using COSINE-100 data with a total exposure of 97.7 kg $$\cdot $$ · years.
Published: 2021
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20. Identification of new isomers in $$^{228}$$ 228 Ac: impact on dark matter searches

Author: K. W. Kim, G. Adhikari, E. Barbosa de Souza, N. Carlin, J. J. Choi, S. Choi, M. Djamal, A. C. Ezeribe, L. E. França, C. Ha, I. S. Hahn, E. J. Jeon, J. H. Jo, W. G. Kang, M. Kauer, H. Kim, H. J. Kim, S. H. Kim, S. K. Kim, W. K. Kim, Y. D. Kim, Y. H. Kim, Y. J. Ko, E. K. Lee, H. Lee, H. S. Lee, H. Y. Lee, I. S. Lee, J. Lee, J. Y. Lee, M. H. Lee, S. H. Lee, S. M. Lee, D. S. Leonard, B. B. Manzato, R. H. Maruyama, R. J. Neal, S. L. Olsen, B. J. Park, H. K. Park, H. S. Park, K. S. Park, R. L. C. Pitta, H. Prihtiadi, S. J. Ra, C. Rott, K. A. Shin, A. Scarff, N. J. C. Spooner, W. G. Thompson, L. Yang, G. H. Yu, and COSINE-100 Collaboration
Subjects: Astrophysics, QB460-466, Nuclear and particle physics. Atomic energy. Radioactivity, QC770-798
Abstract: Abstract We report the identification of metastable isomeric states of $$^{228}$$ 228 Ac at 6.28 keV, 6.67 keV and 20.19 keV, with lifetimes of an order of 100 ns. These states are produced by the $$\beta $$ β -decay of $$^{228}$$ 228 Ra, a component of the $$^{232}$$ 232 Th decay chain, with $$\beta $$ β Q-values of 39.52 keV, 39.13 keV and 25.61 keV, respectively. Due to the low Q-value of $$^{228}$$ 228 Ra as well as the relative abundance of $$^{232}$$ 232 Th and their progeny in low background experiments, these observations potentially impact the low-energy background modeling of dark matter search experiments.
Published: 2021
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21. Lg = 130 nm GAA MBCFETs with three-level stacked In0.53Ga0.47As nanosheets.

Author: H.-B. Jo, I.-G. Lee, J.-M. Baek, S. T. Lee, S.-M. Choi, H.-J. Kim, H.-S. Jeong, W.-S. Park, J.-H. Yoo, H.-Y. Lee, D. Y. Yun, S.-W. Son, D.-H. Ko, Tae-Woo Kim, H.-M. Kwon, S.-K. Kim, Jun-Gyu Kim, J. Yun, T. Kim, J. H. Lee, J.-H. Lee, C.-S. Shin, K.-S. Seo, and Dae-Hyun Kim
Published: 2022
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22. Development of a data-driven COVID-19 prognostication tool to inform triage and step-down care for hospitalised patients in Hong Kong: a population-based cohort study

Author: Eva L. H. Tsui, Carrie S. M. Lui, Pauline P. S. Woo, Alan T. L. Cheung, Peggo K. W. Lam, Van T. W. Tang, C. F. Yiu, C. H. Wan, and Libby H. Y. Lee
Subjects: COVID-19, Prognostic, Prediction, Clinical outcome, Disease severity, Triage, Computer applications to medicine. Medical informatics, R858-859.7
Abstract: Abstract Background This is the first study on prognostication in an entire cohort of laboratory-confirmed COVID-19 patients in the city of Hong Kong. Prognostic tool is essential in the contingency response for the next wave of outbreak. This study aims to develop prognostic models to predict COVID-19 patients’ clinical outcome on day 1 and day 5 of hospital admission. Methods We did a retrospective analysis of a complete cohort of 1037 COVID-19 laboratory-confirmed patients in Hong Kong as of 30 April 2020, who were admitted to 16 public hospitals with their data sourced from an integrated electronic health records system. It covered demographic information, chronic disease(s) history, presenting symptoms as well as the worst clinical condition status, biomarkers’ readings and Ct value of PCR tests on Day-1 and Day-5 of admission. The study subjects were randomly split into training and testing datasets in a 8:2 ratio. Extreme Gradient Boosting (XGBoost) model was used to classify the training data into three disease severity groups on Day-1 and Day-5. Results The 1037 patients had a mean age of 37.8 (SD ± 17.8), 53.8% of them were male. They were grouped under three disease outcome: 4.8% critical/serious, 46.8% stable and 48.4% satisfactory. Under the full models, 30 indicators on Day-1 and Day-5 were used to predict the patients’ disease outcome and achieved an accuracy rate of 92.3% and 99.5%. With a trade-off between practical application and predictive accuracy, the full models were reduced into simpler models with seven common specific predictors, including the worst clinical condition status (4-level), age group, and five biomarkers, namely, CRP, LDH, platelet, neutrophil/lymphocyte ratio and albumin/globulin ratio. Day-1 model’s accuracy rate, macro-/micro-averaged sensitivity and specificity were 91.3%, 84.9%/91.3% and 96.0%/95.7% respectively, as compared to 94.2%, 95.9%/94.2% and 97.8%/97.1% under Day-5 model. Conclusions Both Day-1 and Day-5 models can accurately predict the disease severity. Relevant clinical management could be planned according to the predicted patients’ outcome. The model is transformed into a simple online calculator to provide convenient clinical reference tools at the point of care, with an aim to inform clinical decision on triage and step-down care.
Published: 2020
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23. The Medial Offshore Record of Explosive Volcanism Along the Central to Eastern Aegean Volcanic Arc: 1. Tephrostratigraphic Correlations

Author: S. Kutterolf, A. Freundt, T. H. Hansteen, R. Dettbarn, F. Hampel, C. Sievers, C. Wittig, S. R. Allen, T. H. Druitt, J. McPhie, P. Nomikou, K. Pank, J. C. Schindlbeck‐Belo, K.‐L. Wang, H.‐Y. Lee, and B. Friedrichs
Subjects: Tephrostratigraphy, Aegean Arc, Chemical fingerprinting, volcanology, Geophysics. Cosmic physics, QC801-809, Geology, QE1-996.5
Abstract: Abstract The Milos, Christiana‐Santorini‐Kolumbo (CSK) and Kos‐Yali‐Nisyros (KYN) volcanic complexes of the Aegean Volcanic Arc have repeatedly produced highly explosive eruptions from at least ∼360 ka into historic times and still show recent unrest. We present the marine tephra record from an array of 50, up to 7.4 m long, sediment cores along the arc collected in 2017 during RV Poseidon cruise POS513, which complements earlier work on distal to ultra‐distal eastern Mediterranean sediment cores. A unique set of glass‐shard trace element (LA‐ICPMS) compositions complements our major element (EMP) data on 220 primary ash layers and 40 terrestrial samples to support geochemical fingerprinting for correlations with 19 known tephras from all three volcanic complexes and with the 39 ka Campanian Ignimbrite from the Campi Flegrei, Italy. The correlations include 11 eruptions from CSK (Kameni, Kolumbo 1650, Minoan, Cape Riva, Cape Tripiti, Upper Scoriae 1 and 2, Middle Pumice, Cape Thera, Lower Pumice, Cape Therma 3). We identify a previously unknown widespread tephra from a plinian eruption on Milos (Firiplaka Tephra). Near the KYN we correlate marine tephras with the Kos Plateau Tuff, the Yali 1 and Yali 2 tephras, and the Upper and Lower Pumice on Nisyros. Between these two major tephras, we found two tephras from Nisyros not yet observed on land. The four Nisyros tephras form a systematic trend toward more evolved magma compositions. In the companion paper we use the tephrostratigraphic framework established here to constrain new eruption ages and magnitudes as a contribution to volcanic hazard assessment.
Published: 2021
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24. Investigation of First Fire Effect on VTH Stability and Endurance in GeCTe Selector.

Author: P. C. Chang, P. J. Liao, D. W. Heh, C. Lee, D. H. Hou, Elia Ambrosi, C. H. Wu, H. Y. Lee, J. H. Lee, and Xinyu Bao
Published: 2022
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25. Zircon and Melt Extraction From a Long‐Lived and Vertically Extensive Magma System Underneath Ilopango Caldera (El Salvador)

Author: A. Cisneros de León, A. K. Schmitt, S. Kutterolf, J. C. Schindlbeck‐Belo, W. Hernández, K. W. W. Sims, J. Garrison, L. B. Kant, B. Weber, K.‐L. Wang, H.‐Y. Lee, and R. B. Trumbull
Subjects: Central America, Geochemistry, Oxygen isotopes, SIMS, U‐series, Zircon, Geophysics. Cosmic physics, QC801-809, Geology, QE1-996.5
Abstract: Abstract The Tierra Blanca (TB) eruptive suite comprises the last four major eruptions of Ilopango caldera in El Salvador (≤45 ka), including the youngest Tierra Blanca Joven eruption (TBJ; ∼106 km3): the most voluminous event during the Holocene in Central America. Despite the protracted and productive history of explosive silicic eruptions at Ilopango caldera, many aspects regarding the longevity and the prevailing physicochemical conditions of the underlying magmatic system remain unknown. Zircon 238U‐230Th geochronology of the TB suite (TBJ, TB2, TB3, and TB4) reveals a continuous and overlapping crystallization history among individual eruptions, suggesting persistent melt presence in thermally and compositionally distinct magma reservoirs over the last ca. 80 kyr. The longevity of zircon is in contrast to previously determined crystallization timescales of
Published: 2021
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26. Different Disease Endotypes in Phenotypically Similar Vasculitides Affecting Small-to-Medium Sized Blood Vessels

Author: Erin E. Gill, Maren L. Smith, Kristen M. Gibson, Kimberly A. Morishita, Amy H. Y. Lee, Reza Falsafi, Jinko Graham, Dirk Foell, Susanne M. Benseler, Colin J. Ross, Raashid A. Luqmani, David A. Cabral, Robert E. W. Hancock, Kelly L. Brown, and The PedVas Initiative Investigators
Subjects: vasculitis, neutrophils, transcriptome, inflammation, ANCA, Immunologic diseases. Allergy, RC581-607
Abstract: Objectives: Chronic primary vasculitis describes a group of complex and rare diseases that are characterized by blood vessel inflammation. Classification of vasculitis subtypes is based predominantly on the size of the involved vessels and clinical phenotype. There is a recognized need to improve classification, especially for small-to-medium sized vessel vasculitides, that, ideally, is based on the underlying biology with a view to informing treatment.Methods: We performed RNA-Seq on blood samples from children (n = 41) and from adults (n = 11) with small-to-medium sized vessel vasculitis, and used unsupervised hierarchical clustering of gene expression patterns in combination with clinical metadata to define disease subtypes.Results: Differential gene expression at the time of diagnosis separated patients into two primary endotypes that differed in the expression of ~3,800 genes in children, and ~1,600 genes in adults. These endotypes were also present during disease flares, and both adult and pediatric endotypes could be discriminated based on the expression of just 20 differentially expressed genes. Endotypes were associated with distinct biological processes, namely neutrophil degranulation and T cell receptor signaling.Conclusions: Phenotypically similar subsets of small-to-medium sized vessel vasculitis may have different mechanistic drivers involving innate vs. adaptive immune processes. Discovery of these differentiating immune features provides a mechanistic-based alternative for subclassification of vasculitis.
Published: 2021
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27. Peptide 1018 inhibits swarming and influences Anr-regulated gene expression downstream of the stringent stress response in Pseudomonas aeruginosa.

Author: Lauren V Wilkinson, Morgan A Alford, Shannon R Coleman, Bing C Wu, Amy H Y Lee, Travis M Blimkie, Manjeet Bains, Reza Falsafi, Daniel Pletzer, and Robert E W Hancock
Subjects: Medicine, Science
Abstract: Pseudomonas aeruginosa is a ubiquitous opportunistic pathogen that causes considerable human morbidity and mortality, particularly in nosocomial infections and individuals with cystic fibrosis. P. aeruginosa can adapt to surface growth by undergoing swarming motility, a rapid multicellular movement that occurs on viscous soft surfaces with amino acids as a nitrogen source. Here we tested the small synthetic host defense peptide, innate defense regulator 1018, and found that it inhibited swarming motility at concentrations as low as 0.75 μg/ml, well below the MIC for strain PA14 planktonic cells (64 μg/ml). A screen of the PA14 transposon insertion mutant library revealed 29 mutants that were more tolerant to peptide 1018 during swarming, five of which demonstrated significantly greater swarming than the WT in the presence of peptide. Transcriptional analysis (RNA-Seq) of cells that were inoculated on swarming plates containing 1.0 μg/ml peptide revealed differential expression of 1,190 genes compared to cells swarming on plates without peptide. Furthermore, 1018 treatment distinctly altered the gene expression profile of cells when compared to that untreated cells in the centre of the swarm colonies. Peptide-treated cells exhibited changes in the expression of genes implicated in the stringent stress response including those regulated by anr, which is involved in anaerobic adaptation, indicative of a mechanism by which 1018 might inhibit swarming motility. Overall, this study illustrates potential mechanisms by which peptide 1018 inhibits swarming surface motility, an important bacterial adaptation associated with antibiotic resistance, virulence, and dissemination of P. aeruginosa.
Published: 2021
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28. Measurement of High-energy Cosmic-Ray Proton Spectrum from the ISS-CREAM Experiment

Author: G. H. Choi, E. S. Seo, S. Aggarwal, Y. Amare, D. Angelaszek, D. P. Bowman, Y. C. Chen, M. Copley, L. Derome, L. Eraud, C. Falana, A. Gerrety, J. H. Han, H. G. Huh, A. Haque, Y. S. Hwang, H. J. Hyun, H. B. Jeon, J. A. Jeon, S. Jeong, S. C. Kang, H. J. Kim, K. C. Kim, M. H. Kim, H. Y. Lee, J. Lee, M. H. Lee, L. Lu, J. P. Lundquist, L. Lutz, A. Menchaca-Rocha, O. Ofoha, H. Park, I. H. Park, J. M. Park, N. Picot-Clemente, R. Scrandis, J. R. Smith, R. Takeishi, N. Vedenkin, P. Walpole, R. P. Weinmann, H. Wu, J. Wu, Z. Yin, Y. S. Yoon, and H. G. Zhang
Published: 2022
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29. Factors Influencing Teleworking Productivity – a Natural Experiment during the COVID-19 Pandemic

Author: Xiao Shi, Anne Vernez Moudon, Brian H. Y. Lee, Qing Shen, and Xuegang (Jeff) Ban
Subjects: Transportation and communications, HE1-9990, Urban groups. The city. Urban sociology, HT101-395
Abstract: Of 2174 surveyed adults who were teleworking following the implementation of a Covid-19 work-from-home policy, 23.8% reported an increase in productivity, 37.6% no change, and 38.6% a decrease in productivity compared to working at their prior workplace. After controlling for feelings of depression and anxiety likely caused by pandemic-related circumstances, the socioeconomic characteristics associated with no change or an increase in productivity after shifting to teleworking included being older; not employed in higher education; having lower education attainment; and not living with children. Respondents with longer commute trips in single-occupancy vehicles prior to teleworking were more likely to be more productive but those with longer commute by walking were not. Lifestyle changes associated with increased productivity included better sleep quality, spending less time on social media, but more time on personal hobbies.
Published: 2020
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30. The Stringent Stress Response Controls Proteases and Global Regulators under Optimal Growth Conditions in Pseudomonas aeruginosa

Author: Daniel Pletzer, Travis M. Blimkie, Heidi Wolfmeier, Yicong Li, Arjun Baghela, Amy H. Y. Lee, Reza Falsafi, and Robert E. W. Hancock
Subjects: ppGpp, relA, spoT, aprA, global transcriptional regulator, global regulatory networks, Microbiology, QR1-502
Abstract: ABSTRACT The bacterial stringent stress response, mediated by the signaling molecule guanosine tetraphosphate, ppGpp, has recently gained attention as being important during normal cellular growth and as a potential new therapeutic target, which warrants detailed mechanistic understanding. Here, we used intracellular protein tracking in Pseudomonas aeruginosa PAO1, which indicated that RelA was bound to the ribosome, while SpoT localized at the cell poles. Transcriptome sequencing (RNA-Seq) was used to investigate the transcriptome of a ppGpp-deficient strain under nonstressful, nutrient-rich broth conditions where the mutant grew at the same rate as the parent strain. In the exponential growth phase, the lack of ppGpp led to >1,600 transcriptional changes (fold change cutoff of ±1.5), providing further novel insights into the normal physiological role of ppGpp. The stringent response was linked to gene expression of various proteases and secretion systems, including aprA, PA0277, impA, and clpP2. The previously observed reduction in cytotoxicity toward red blood cells in a stringent response mutant appeared to be due to aprA. Investigation of an aprA mutant in a murine skin infection model showed increased survival rates of mice infected with the aprA mutant, consistent with previous observations that stringent response mutants have reduced virulence. In addition, the overexpression of relA, but not induction of ppGpp with serine hydroxamate, dysregulated global transcriptional regulators as well as >30% of the regulatory networks controlled by AlgR, OxyR, LasR, and AmrZ. Together, these data expand our knowledge about ppGpp and its regulatory network and role in environmental adaptation. It also confirms its important role throughout the normal growth cycle of bacteria. IMPORTANCE Microorganisms need to adapt rapidly to survive harsh environmental changes. Here, we showed the broad influence of the highly studied bacterial stringent stress response under nonstressful conditions that indicate its general physiological importance and might reflect the readiness of bacteria to respond to and activate acute stress responses. Using RNA-Seq to investigate the transcriptional network of Pseudomonas aeruginosa cells revealed that >30% of all genes changed expression in a stringent response mutant under optimal growth conditions. This included genes regulated by global transcriptional regulators and novel downstream effectors. Our results help to understand the importance of this stress regulator in bacterial lifestyle under relatively unstressed conditions. As such, it draws attention to the consequences of targeting this ubiquitous bacterial signaling molecule.
Published: 2020
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31. Systems Biology Approaches to Understanding the Human Immune System

Author: Bhavjinder K. Dhillon, Maren Smith, Arjun Baghela, Amy H. Y. Lee, and Robert E. W. Hancock
Subjects: systems biology, multi-omic integration, transcriptomics, innate immunity, immune ontogeny, host-pathogen interaction, Immunologic diseases. Allergy, RC581-607
Abstract: Systems biology is an approach to interrogate complex biological systems through large-scale quantification of numerous biomolecules. The immune system involves >1,500 genes/proteins in many interconnected pathways and processes, and a systems-level approach is critical in broadening our understanding of the immune response to vaccination. Changes in molecular pathways can be detected using high-throughput omics datasets (e.g., transcriptomics, proteomics, and metabolomics) by using methods such as pathway enrichment, network analysis, machine learning, etc. Importantly, integration of multiple omic datasets is becoming key to revealing novel biological insights. In this perspective article, we highlight the use of protein-protein interaction (PPI) networks as a multi-omics integration approach to unravel information flow and mechanisms during complex biological events, with a focus on the immune system. This involves a combination of tools, including: InnateDB, a database of curated interactions between genes and protein products involved in the innate immunity; NetworkAnalyst, a visualization and analysis platform for InnateDB interactions; and MetaBridge, a tool to integrate metabolite data into PPI networks. The application of these systems techniques is demonstrated for a variety of biological questions, including: the developmental trajectory of neonates during the first week of life, mechanisms in host-pathogen interaction, disease prognosis, biomarker discovery, and drug discovery and repurposing. Overall, systems biology analyses of omics data have been applied to a variety of immunology-related questions, and here we demonstrate the numerous ways in which PPI network analysis can be a powerful tool in contributing to our understanding of the immune system and the study of vaccines.
Published: 2020
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32. Rhinovirus Infection Drives Complex Host Airway Molecular Responses in Children With Cystic Fibrosis

Author: Kak-Ming Ling, Luke W. Garratt, Erin E. Gill, Amy H. Y. Lee, Patricia Agudelo-Romero, Erika N. Sutanto, Thomas Iosifidis, Tim Rosenow, Stuart E. Turvey, Timo Lassmann, Robert E. W. Hancock, Anthony Kicic, and Stephen M. Stick
Subjects: cystic fibrosis, RV, airway epithelial cells, transcriptomic, innate immune response, Immunologic diseases. Allergy, RC581-607
Abstract: Early-life viral infections are responsible for pulmonary exacerbations that can contribute to disease progression in young children with cystic fibrosis (CF). The most common respiratory viruses detected in the CF airway are human rhinoviruses (RV), and augmented airway inflammation in CF has been attributed to dysregulated airway epithelial responses although evidence has been conflicting. Here, we exposed airway epithelial cells from children with and without CF to RV in vitro. Using RNA-Seq, we profiled the transcriptomic differences of CF and non-CF airway epithelial cells at baseline and in response to RV. There were only modest differences between CF and non-CF cells at baseline. In response to RV, there were 1,442 and 896 differentially expressed genes in CF and non-CF airway epithelial cells, respectively. The core antiviral responses in CF and non-CF airway epithelial cells were mediated through interferon signaling although type 1 and 3 interferon signaling, when measured, were reduced in CF airway epithelial cells following viral challenge consistent with previous reports. The transcriptional responses in CF airway epithelial cells were more complex than in non-CF airway epithelial cells with diverse over-represented biological pathways, such as cytokine signaling and metabolic and biosynthetic pathways. Network analysis highlighted that the differentially expressed genes of CF airway epithelial cells' transcriptional responses were highly interconnected and formed a more complex network than observed in non-CF airway epithelial cells. We corroborate observations in fully differentiated air–liquid interface (ALI) cultures, identifying genes involved in IL-1 signaling and mucin glycosylation that are only dysregulated in the CF airway epithelial response to RV infection. These data provide novel insights into the CF airway epithelial cells' responses to RV infection and highlight potential pathways that could be targeted to improve antiviral and anti-inflammatory responses in CF.
Published: 2020
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33. Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry

Author: Jitendra PS. Sawhney, Veerappa A. Kothiwale, Vikas Bisne, Rajashekhar Durgaprasad, Praveen Jadhav, Manoj Chopda, Velam Vanajakshamma, Ramdhan Meena, Govindan Vijayaraghavan, Kamaldeep Chawla, Jagan Allu, Karen S. Pieper, A. John Camm, Ajay K. Kakkar, Jean-Pierre Bassand, David A. Fitzmaurice, Samuel Z. Goldhaber, Shinya Goto, Sylvia Haas, Werner Hacke, Lorenzo G. Mantovani, Frank Misselwitz, Alexander G.G. Turpie, Martin van Eickels, Freek W.A. Verheugt, Gloria Kayani, Keith A.A. Fox, Bernard J. Gersh, Hector Lucas Luciardi, Harry Gibbs, Marianne Brodmann, Frank Cools, Antonio Carlos Pereira Barretto, Stuart J. Connolly, Alex Spyropoulos, John Eikelboom, Ramon Corbalan, Dayi Hu, Petr Jansky, Jørn Dalsgaard Nielsen, Hany Ragy, Pekka Raatikainen, Jean-Yves Le Heuzey, Harald Darius, Matyas Keltai, Sanjay Kakkar, Jitendra Pal Singh Sawhney, Giancarlo Agnelli, Giuseppe Ambrosio, Yukihiro Koretsune, Carlos Jerjes Sánchez Díaz, Hugo Ten Cate, Dan Atar, Janina Stepinska, Elizaveta Panchenko, Toon Wei Lim, Barry Jacobson, Seil Oh, Xavier Viñolas, Marten Rosenqvist, Jan Steffel, Pantep Angchaisuksiri, Ali Oto, Alex Parkhomenko, Wael Al Mahmeed, David Fitzmaurice, D.Y. Hu, K.N. Chen, Y.S. Zhao, H.Q. Zhang, J.Z. Chen, S.P. Cao, D.W. Wang, Y.J. Yang, W.H. Li, Y.H. Yin, G.Z. Tao, P. Yang, Y.M. Chen, S.H. He, Ying Wang, Yong Wang, G.S. Fu, X. Li, T.G. Wu, X.S. Cheng, X.W. Yan, R.P. Zhao, M.S. Chen, L.G. Xiong, P. Chen, Y. Jiao, Y. Guo, L. Xue, F.Z. Wang, H. Li, Z.M. Yang, C.L. Bai, J. Chen, J.Y. Chen, X. Chen, S. Feng, Q.H. Fu, X.J. Gao, W.N. Guo, R.H. He, X.A. He, X.S. Hu, X.F. Huang, B. Li, J. Li, L. Li, Y.H. Li, T.T. Liu, W.L. Liu, Y.Y. Liu, Z.C. Lu, X.L. Luo, T.Y. Ma, J.Q. Peng, X. Sheng, X.J. Shi, Y.H. Sun, G. Tian, K. Wang, L. Wang, R.N. Wu, Q. Xie, R.Y. Xu, J.S. Yang, L.L. Yang, Q. Yang, Y. Ye, H.Y. Yu, J.H. Yu, T. Yu, H. Zhai, Q. Zhan, G.S. Zhang, Q. Zhang, R. Zhang, Y. Zhang, W.Y. Zheng, B. Zhou, Z.H. Zhou, X.Y. Zhu, S. Kakkar, J.P.S. Sawhney, P. Jadhav, R. Durgaprasad, A.G. Ravi Shankar, R.K. Rajput, K. Bhargava, R. Sarma, A. Srinivas, D. Roy, U.M. Nagamalesh, M. Chopda, R. Kishore, G. Kulkarni, P. Chandwani, R.A. Pothiwala, M. Padinhare Purayil, S. Shah, K. Chawla, V.A. Kothiwale, B. Raghuraman, G. Vijayaraghavan, V.M. Vijan, G. Bantwal, V. Bisne, A. Khan, J.B. Gupta, S. Kumar, D. Jain, S. Abraham, D. Adak, A. Barai, H. Begum, P. Bhattacharjee, M. Dargude, D. Davies, B. Deshpande, P. Dhakrao, V. Dhyani, S. Duhan, M. Earath, A. Ganatra, S. Giradkar, V. Jain, R. Karthikeyan, L. Kasala, S. Kaur, S. Krishnappa, A. Lawande, B. Lokesh, N. Madarkar, R. Meena, P. More, D. Naik, K. Prashanth, M. Rao, N.M. Rao, N. Sadhu, D. Shah, M. Sharma, P. Shiva, S. Singhal, S. Suresh, V. Vanajakshamma, S.G. Panse, Y. Koretsune, S. Kanamori, K. Yamamoto, K. Kumagai, Y. Katsuda, K. Sadamatsu, F. Toyota, Y. Mizuno, I. Misumi, H. Noguchi, S. Ando, T. Suetsugu, M. Minamoto, Hiroshi Oda, K. Shiraishi, S. Adachi, K. Chiba, H. Norita, M. Tsuruta, T. Koyanagi, H. Ando, T. Higashi, K. Okada, S. Azakami, S. Komaki, K. Kumeda, T. Murayama, J. Matsumura, Y. Oba, R. Sonoda, K. Goto, K. Minoda, Y. Haraguchi, H. Suefuji, H. Miyagi, H. Kato, Tadashi Nakamura, Tsugihiro Nakamura, H. Nandate, R. Zaitsu, Yoshihisa Fujiura, A. Yoshimura, H. Numata, J. Ogawa, H. Tatematsu, Y. Kamogawa, K. Murakami, Y. Wakasa, M. Yamasawa, H. Maekawa, S. Abe, H. Kihara, S. Tsunoda, Katsumi Saito, Kazuyuki Saito, T. Fudo, K. Obunai, H. Tachibana, I. Oba, T. Kuwahata, S. Higa, M. Gushiken, T. Eto, H. Yoshida, D. Ikeda, Yoshitake Fujiura, M. Ishizawa, M. Nakatsuka, K. Murata, C. Ogurusu, M. Shimoyama, M. Akutsu, I. Takamura, F. Hoshino, N. Yokota, T. Iwao, K. Tsuchida, M. Takeuchi, Y. Hatori, Y. Kitami, Yoichi Nakamura, R. Oyama, M. Ageta, Hiroyuki Oda, Y. Go, K. Mishima, T. Unoki, S. Morii, Yuhei Shiga, H. Sumi, T. Nagatomo, K. Sanno, K. Fujisawa, Y. Atsuchi, T. Nagoshi, T. Seto, T. Tabuchi, M. Kameko, K. Nii, K. Oshiro, H. Takezawa, S. Nagano, N. Miyamoto, M. Iwaki, Yuichiro Nakamura, M. Fujii, M. Okawa, Masahiko Abe, Masatake Abe, Mitsunori Abe, T. Saito, T. Mito, K. Nagao, J. Minami, T. Mita, I. Sakuma, T. Taguchi, S. Marusaki, H. Doi, M. Tanaka, T. Fujito, M. Matsuta, T. Kusumoto, S. Kakinoki, K. Ashida, N. Yoshizawa, J. Agata, O. Arasaki, M. Manita, M. Ikemura, S. Fukuoka, H. Murakami, S. Matsukawa, Y. Hata, T. Taniguchi, T. Ko, H. Kubo, M. Imamaki, M. Akiyama, M. Inagaki, H. Odakura, T. Ueda, Y. Katsube, A. Nakata, H. Watanabe, M. Techigawara, M. Igarashi, K. Taga, T. Kimura, S. Tomimoto, M. Shibuya, M. Nakano, K. Ito, T. Seo, S. Hiramitsu, H. Hosokawa, M. Hoshiai, M. Hibino, K. Miyagawa, Hajime Horie, N. Sugishita, Yukio Shiga, A. Soma, K. Neya, Tetsuro Yoshida, Tomoki Yoshida, M. Mizuguchi, M. Ishiguro, T. Minagawa, M. Wada, H. Mukawa, F. Okuda, S. Nagasaka, Y. Abe, Sen Adachi, Susumu Adachi, T. Adachi, K. Akahane, T. Amano, K. Aoki, T. Aoyama, H. Arai, S. Arima, T. Arino, H. Asano, T. Asano, J. Azuma, T. Baba, T. Betsuyaku, H. Chibana, H. Date, J. Doiuchi, Y. Emura, M. Endo, Y. Fujii, R. Fujiki, A. Fujisawa, Y. Fujisawa, T. Fukuda, T. Fukui, N. Furukawa, T. Furukawa, W. Furumoto, T. Goto, M. Hamaoka, N. Hanazono, K. Hasegawa, T. Hatsuno, Y. Hayashi, K. Higuchi, K. Hirasawa, H. Hirayama, M. Hirose, S. Hirota, M. Honda, Hideki Horie, T. Ido, O. Iiji, H. Ikeda, K. Ikeda, K. Ikeoka, M. Imaizumi, H. Inaba, T. Inoue, F. Iseki, A. Ishihara, N. Ishioka, N. Ito, T. Iwase, H. Kakuda, J. Kamata, H. Kanai, H. Kanda, M. Kaneko, H. Kano, T. Kasai, T. Kato, Y. Kato, Y. Kawada, K. Kawai, K. Kawakami, S. Kawakami, T. Kawamoto, S. Kawano, J. Kim, T. Kira, H. 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Sterry, T. Wong, M. Boon, R. Bunney, R. Haria-Shah, R.T. Baron, S. Davies, T. Schatzberger, N. Hargreaves, T. Stephenson, H. Choi, R. Batson, L. Lucraft, T. Myhill, S. Estifano, D. Geatch, J. Wilkinson, R. Veale, K. Forshaw, T. Davies, K. Zaman, P. Vinson, C. Liley, M. Bandrapalli, P. McGinty, R. Wastling, P. McEleny, A. Beattie, P. Cooke, M. Wong, J. Gunasegaram, M. Pugsley, S. Ahmad, C. A'Court, J. Ayers, J. Bennett, S. Cartwright, S. Dobson, C. Dooldeniya, A. Flynn, R. Fox, J. Goram, A. Halpin, A. Hay, P. Jacobs, L. Jeffers, L. Lomax, I. Munro, R. Muvva, M. Nadaph, K. Powell, S. Randfield, D. Redpath, R. Reed, M. Rickenbach, G. Rogers, P.B. Saunders, C. Seamark, J. Shewring, P. Simmons, H. Simper, H. Stoddart, A. Sword, N. Thomas, A. Thomson, H. Gibbs, A. Blenkhorn, B. Singh, W. Van Gaal, W. Abhayaratna, R. Lehman, P. Roberts-Thomson, J. Kilian, D. Coulshed, A. Catanchin, D. Colquhoun, H. Kiat, D. Eccleston, J. French, L. Zimmett, B. Ayres, T. Phan, P. Blombery, D. Crimmins, D. O'Donnell, A. Choi, P. Astridge, M. Arstall, N. Jepson, M. Binnekamp, A. Lee, J. Rogers, G. Starmer, P. Carroll, J. Faunt, A. Aggarwala, L. Barry, C. Batta, R. Beveridge, A. Black, M. Bonner, J. Boys, E. Buckley, M. Campo, L. Carlton, A. Connelly, B. Conway, D. Cresp, H. Dimitri, S. Dixon, M. Dolman, M. Duroux, M. Eskandari, R. Eslick, A. Ferreira-Jardim, T. Fetahovic, D. Fitzpatrick, R. Geraghty, J. Gibbs, T. Grabek, M.H. Modi, K. Hayes, M.P. Hegde, L. Hesketh, B. Hoffmann, B. Jacobson, K. Johnson, C. Juergens, I. Kassam, V. Lawlor, M. Lehman, S. Lehman, D. Leung, S. Mackay, M. MacKenzie, C. McCarthy, C. McIntosh, L. McKeon, H. Morrison, C. Mussap, J.-D. Myers, V. Nagalingam, G. Oldfield, V. O'May, J. Palmer, L. Parsons, K. Patching, T. Patching, V. Paul, M. Plotz, S. Preston, H. Rashad, M. Ratcliffe, S. Raynes, J. Rose, L. Sanders, M. Seremetkoska, H. Setio, S. Shone, P. Shrestha, C. Singh, C. Singleton, N. Stoyanov, S. Sutcliffe, K. Swaraj, J. Tarrant, S. Thompson, I.M. Tsay, M. Vorster, A. Waldman, L. Wallis, E. Wilford, K. Wong, S.J. Connolly, A. Spyropoulos, J. Eikelboom, R. Luton, M. Gupta, A.S. Pandey, S. Cheung, R. Leader, P. Beaudry, F. Ayala-Paredes, J. Berlingieri, J. Heath, G. Poirier, M. Du Preez, R. Nadeau, G. Dresser, R. Dhillon, T. Hruczkowski, B. Schweitzer, B. Coutu, P. Angaran, P. MacDonald, S. Vizel, S. Fikry, R. Parkash, A. Lavoie, J. Cha, B. Ramjattan, J. Bonet, K. Ahmad, L. Aro, T. Aves, K. Beaudry, C. Bergeron, J. Bigcanoe, N. Bignell, L. Breakwell, E. Burke, L. Carroll, B. Clarke, T. Cleveland, S. Daheb, P. Dehghani, I. Denis, Z. Djaidani, P. Dorian, S. Douglass, J. Dunnigan, A. Ewert, D. Farquhar, A. Fearon, L. Ferleyko, D. Fournier, B. Fox, M.-C. Grenier, W. Gulliver, K. Haveman, C. Hines, K. Hines, A.M. Jackson, C. Jean, G. Jethoo, R. Kahlon, S. Kelly, R. Kim, V. Korley, J. Kornder, L. Kwan, J. Largy, C. Lewis, S. Lewis, I. Mangat, R. Moor, J. Navratil, I. Neas, J. Otis, R. Otis, M. Pandey, F. Petrie, A. Pinter, M. Raines, P. Roberts, M. Robinson, G. Sas, S. Schulman, L. Snell, S. Spearson, J. Stevenson, T. Trahey, S. Wong, D. Wright, H. Ragy, A. Abd El-Aziz, S.K. Abou Seif, M.G. El Din, S. El Etriby, A. Elbahry, A. El-Etreby, M. Elkhadem, A. Katta, T. Khairy, A. Mowafy, M. Nawar, A. Ohanissian, A. Reda, M. Reda, H. Salem, N. Sami, S. Samir, M. Setiha, M. Sobhy, A. Soliman, N. Taha, M. Tawfik, E. Zaatout, D. Kettles, J. Bayat, H. Siebert, A. Horak, Y. Kelfkens, R. Garda, T. Pillay, M. Guerra, L. van Zyl, H. Theron, A. Murray, R. Louw, D. Greyling, P. Mntla, V. Ueckermann, R. Loghdey, S. Ismail, F. Ahmed, J. Engelbrecht, A. Ramdass, S. Maharajh, W. Oosthuysen, G. Angel, C. Bester, M. Booysen, C. Boshoff, C. Cannon, S. Cassimjee, C. Chami, G. Conway, A. Davids, L. de Meyer, G. Du Plessis, T. Ellis, L. Henley, M. Karsten, E. Loyd, J. Marks, L. Mavhusa, M. Mostert, A. Page, L. Rikhotso, M. Salie, J. Sasto, F. Shaik, A. Skein, L. Smith, G. Tarr, T. Tau, F. van Zyl, W. Al Mahmeed, G. Yousef, A. Agrawal, M. Nathani, M. Ibrahim, E.M. Esheiba, R. Singh, A. Naguib, M. Abu-Mahfouz, M. Al Omairi, A. Al Naeemi, R. Maruthanayagam, N. Bazargani, A. Wassef, R. Gupta, M. Khan, B. Subbaraman, A. Abdul, A. Al Mulla, S. El Bardisy, P. Haridas, S. Jadhav, K. Magdaluyo, M. Makdad, I. Maqsood, R. Mohamed, N. Sharma, R. Sharma, M. Thanzeel, S.Z. Goldhaber, R. Canosa, P. Rama, E. Blumberg, J. Garcia, P. Mullen, V. Wilson, A. Quick, K. Ferrick, W.M. Kutayli, M. Cox, M. Franco, S. Falkowski, R. Mendelson, M. Williams, S. Miller, S. Beach, A. Alfieri, T. Gutowski, I. Haque, R. Reddy, W. Ahmed, P. Delafontaine, D. Diercks, D. Theodoro, K. Remmel, M. Alberts, R. Ison, H. Noveck, P. Duffy, S. Pitta, D. Nishijima, C. Treasure, N. Asafu-Adjaye, K. Ball, M. Bartlett, M. Bentley, S. Bowers, A. Brown, A. Browne, J. Cameron-Watts, M. Canova, D. Cassidy, K. Cervellione, S. Congal, J. DePauw, A. Dickerson, M. Eley, L. Evans, S. Felpel, K. Ferdinand, D. Fielder, P. Gentry, A. Haideri, F. Hakimi, T. Harbour, E. Hartranft, B. Hawkins, M. Headlee, L. Henson, C. Herrick, T. Hicks, S. Jasinski, A. Jones, L. Jones, P. Jones, S. Karl, M. Keeling, J. Kerr, P. Knowles, J. Langdon, M. Lay, J.A. Lee, T. Lincoln, E. Malone, A. Merliss, D. Merritt, J. Minardo, B. Mooso, C. Orosco, V. Palumbo, M. Parker, T. Parrott, S. Paserchia, G. Pearl, J. Peterson, N. Pickelsimer, T. Purcell, J. Raynor, S. Raziano, C. Richard, T. Richardson, C. Robertson, A. Sage, T. Sanghera, P. Shaw, J. Shoemaker, K. Smith, B. Stephanie, A. Thatcher, H. Theobald, N. Thompson, L. Treasure, T. Tripti, C. Verdi, and V. Worthy
Subjects: Surgery, RD1-811, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Background: The Global Anticoagulant Registry in the FIELD–Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. Methods and results: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012–2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P
Published: 2018
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34. Late Precambrian 'Pre-Glacial' Sedimentation Stage in the Southern Siberian Platform

Author: Z.L. Motova, T.V. Donskaya, D.P. Gladkochub, A.M. Mazukabzov, K.-L. Wang, and H.-Y. Lee
Subjects: Geophysics, Geology
Abstract: —We present new data on the chemical composition of the late Precambrian rocks in the upper part of the regional Balaganakh stratigraphic horizon (the Nugan Formation at the Baikal segment of the Sayan–Baikal–Patom belt (SBPB) and the Bugarikhta Formation of the Balaganakh Group at the Patom segment of the SBPB) and the U–Pb (LA-ICP-MS) age of detrital zircons from the Bugarikhta Formation. It has been established that the rocks of the Nugan and Bugarikhta formations resulted from the destruction of igneous and metamorphic rocks. The contents and ratios of trace and rare-earth elements in the rocks of the Nugan and Bugarikhta formations indicate a predominance of felsic igneous rocks in the provenance and the presence of rocks of mafic and intermediate compositions at the source of the terrigenous rocks of the Nugan Formation. The U–Pb age of detrital zircons from all rocks of the upper part of the regional Balaganakh Horizon is close to the age of the rocks in the basement of the southern margin of the Siberian Platform, which suggests that this basement was the main source of clastic material in the sedimentation basins. It is argued that the “pre-glacial” (pre-Marinoan) terrigenous deposits of the Nugan and Bugarikhta formations, as well as the deposits of the Ipsit Formation at the Sayan segment of the SBPB, accumulated in the Late Riphean (ca. 720–640 Ma), probably in postrift basins that formed immediately after the separation of Siberia from Laurentia at the early stages of the opening of the Paleoasian Ocean.
Published: 2023
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35. Smad4 SUMOylation is essential for memory formation through upregulation of the skeletal myopathy gene TPM2

Author: Wei L. Hsu, Yun L. Ma, Yen C. Liu, and Eminy H. Y. Lee
Subjects: Smad4, SUMOylation, PIAS1, TPM2 gene, Spatial learning and memory, Skeletal myopathy, Biology (General), QH301-705.5
Abstract: Abstract Background Smad4 is a critical effector of TGF-β signaling that regulates a variety of cellular functions. However, its role in the brain has rarely been studied. Here, we examined the molecular mechanisms underlying the post-translational regulation of Smad4 function by SUMOylation, and its role in spatial memory formation. Results In the hippocampus, Smad4 is SUMOylated by the E3 ligase PIAS1 at Lys-113 and Lys-159. Both spatial training and NMDA injection enhanced Smad4 SUMOylation. Inhibition of Smad4 SUMOylation impaired spatial learning and memory in rats by downregulating TPM2, a gene associated with skeletal myopathies. Similarly, knockdown of TPM2 expression impaired spatial learning and memory, while TPM2 mRNA and protein expression increased after spatial training. Among the TPM2 mutations associated with skeletal myopathies, the TPM2E122K mutation was found to reduce TPM2 expression and impair spatial learning and memory in rats. Conclusions We have identified a novel role of Smad4 SUMOylation and TPM2 in learning and memory formation. These results suggest that patients with skeletal myopathies who carry the TPM2E122K mutation may also have deficits in learning and memory functions.
Published: 2017
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36. A Genome-Wide Knockout Screen in Human Macrophages Identified Host Factors Modulating Salmonella Infection

Author: Amy T. Y. Yeung, Yoon Ha Choi, Amy H. Y. Lee, Christine Hale, Hannes Ponstingl, Derek Pickard, David Goulding, Mark Thomas, Erin Gill, Jong Kyoung Kim, Allan Bradley, Robert E. W. Hancock, and Gordon Dougan
Subjects: CRISPR, Salmonella, bacteria, genome-wide screen, macrophages, Microbiology, QR1-502
Abstract: ABSTRACT A genome-scale CRISPR knockout library screen of THP-1 human macrophages was performed to identify loss-of-function mutations conferring resistance to Salmonella uptake. The screen identified 183 candidate genes, from which 14 representative genes involved in actin dynamics (ACTR3, ARPC4, CAPZB, TOR3A, CYFIP2, CTTN, and NHLRC2), glycosaminoglycan metabolism (B3GNT1), receptor signaling (PDGFB and CD27), lipid raft formation (CLTCL1), calcium transport (ATP2A2 and ITPR3), and cholesterol metabolism (HMGCR) were analyzed further. For some of these pathways, known chemical inhibitors could replicate the Salmonella resistance phenotype, indicating their potential as targets for host-directed therapy. The screen indicated a role for the relatively uncharacterized gene NHLRC2 in both Salmonella invasion and macrophage differentiation. Upon differentiation, NHLRC2 mutant macrophages were hyperinflammatory and did not exhibit characteristics typical of macrophages, including atypical morphology and inability to interact and phagocytose bacteria/particles. Immunoprecipitation confirmed an interaction of NHLRC2 with FRYL, EIF2AK2, and KLHL13. IMPORTANCE Salmonella exploits macrophages to gain access to the lymphatic system and bloodstream to lead to local and potentially systemic infections. With an increasing number of antibiotic-resistant isolates identified in humans, Salmonella infections have become major threats to public health. Therefore, there is an urgent need to identify alternative approaches to anti-infective therapy, including host-directed therapies. In this study, we used a simple genome-wide screen to identify 183 candidate host factors in macrophages that can confer resistance to Salmonella infection. These factors may be potential therapeutic targets against Salmonella infections.
Published: 2019
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37. MetaBridge: enabling network-based integrative analysis via direct protein interactors of metabolites.

Author: Samuel J. Hinshaw, Amy H. Y. Lee, Erin E. Gill, and Robert E. W. Hancock
Published: 2018
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38. Deep Learning-based Monocular Obstacle Avoidance for Unmanned Aerial Vehicle Navigation in Tree Plantations.

Author: H. Y. Lee, Hann Woei Ho, and Ye Zhou
Published: 2021
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39. Occurrence of Emerging Contaminants in Southeast Asian Environments: Present Status, Challenges, and Future Prospects

Author: Theodora H. Y. Lee, Joon Chuah, and Shane A. Snyder
Subjects: Chemistry (miscellaneous), Environmental Chemistry, Chemical Engineering (miscellaneous), Water Science and Technology
Published: 2022
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40. The effect of water temperature on orthostatic tolerance: a randomised crossover trial

Author: Iain T. Parsons, Brooke C. D. Hockin, Omnia M. Taha, Natalie D. Heeney, Erin L. Williams, Vera-Ellen M. Lucci, Rebekah H. Y. Lee, Michael J. Stacey, Nick Gall, Phil Chowienczyk, David R. Woods, and Victoria E. Claydon
Subjects: Lower Body Negative Pressure, Cross-Over Studies, Heart Rate, Endocrine and Autonomic Systems, Orthostatic Intolerance, Temperature, Humans, Water, Blood Pressure, Single-Blind Method, Neurology (clinical), Syncope
Abstract: Purpose Bolus water drinking, at room temperature, has been shown to improve orthostatic tolerance (OT), probably via sympathetic activation; however, it is not clear whether the temperature of the water bolus modifies the effect on OT or the cardiovascular responses to orthostatic stress. The aim of this study was to assess whether differing water temperature of the water bolus would alter time to presyncope and/or cardiovascular parameters during incremental orthostatic stress. Methods Fourteen participants underwent three head-up tilt (HUT) tests with graded lower body negative pressure (LBNP) continued until presyncope. Fifteen minutes prior to each HUT, participants drank a 500 mL bolus of water which was randomised, in single-blind crossover fashion, to either room temperature water (20 °C) (ROOM), ice-cold water (0–3 °C) (COLD) or warm water (45 °C) (WARM). Cardiovascular parameters were monitored continuously. Results There was no significant difference in OT in the COLD (33 ± 3 min; p = 0.3321) and WARM (32 ± 3 min; p = 0.6764) conditions in comparison to the ROOM condition (31 ± 3 min). During the HUT tests, heart rate and cardiac output were significantly reduced (p p Conclusions In healthy controls, bolus cold water drinking results in favourable orthostatic cardiovascular responses during HUT/LBNP without significantly altering OT. Using a cold water bolus may result in additional benefits in patients with orthostatic intolerance above those conferred by bolus water at room temperature (by ameliorating orthostatic tachycardia and enhancing vascular resistance responses). Further research in patients with orthostatic intolerance is warranted.
Published: 2022
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41. The Life-sustaining Treatment Decision of Patients With Terminal Stage of Chronic Pulmonary Disease in Tertiary Care Hospital

Author: H. Lee, Y.M. Bang, H.-Y. Lee, S. Hong, S.H. Kim, M.-Y. Kim, and H.-K. Lee
Published: 2023
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42. Clinical characteristics and associated factors of qualitative olfactory dysfunction

Author: T-S Eo, H Y Lee, H-J Cho, J-H Yoon, M-S Rha, and C-H Kim
Subjects: Otorhinolaryngology, General Medicine
Abstract: Background: Although interest in qualitative olfactory dysfunction (OD), including parosmia and phantosmia, has been increasing since the COVID-19 pandemic, little is known about the clinical characteristics and associated factors of qualitative OD. Methods: Adult patients with subjective smell disturbance who underwent both the olfactory questionnaire and psychophysical olfactory function test were retrospectively enrolled. Demographic and clinical characteristics were analysed according to the presence or absence of parosmia or phantosmia. Results: Among a total of 753 patients with self-reported OD, 60 (8%) and 167 (22.2%) patients reported parosmia and phantosmia, respectively. Younger age and female sex were related to both parosmia and phantosmia. The frequency of parosmia was significantly higher in patients with post-viral OD (17.9%) than in patients with the sinonasal disease (5.5%), whereas that of phantosmia was not different according to aetiologies of OD. Patients with COVID-19 had significantly younger ages and higher TDI scores than those with other viral infections. Remarkably, patients with parosmia or phantosmia had significantly higher TDI scores than those without but experienced more disruption in daily life. In the multivariate analysis, younger age and higher TDI score were identified as independent factors associated with both parosmia and phantosmia, while the viral infection was associated with parosmia but not with phantosmia. Conclusions: Patients with OD who have parosmia or phantosmia have higher odour sensitivity than those who do not, but experience more deterioration in the quality of life. Viral infection is a risk factor for parosmia but not for phantosmia.
Published: 2023
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43. Data report: chemical compositions of marine tephra layers in the Indian Ocean, IODP Expeditions 353 and 362

Author: S.O. Kutterolf, J.C. Schindlbeck, K. Pank, K-L. Wang, and H-Y. Lee
Abstract: We report on a total of 310 samples from marine sediments drilled in the Indian Ocean that were analyzed for glass shard compositions. Samples are mainly from International Ocean Discovery Program Expeditions 353 and 362 but are complemented by samples from Expedition 354; Ocean Drilling Program Legs 183, 121, 120, 119, 116, and 115; and Deep Sea Drilling Project Leg 22. We performed 4327 successful single glass shard analyses with the electron microprobe for major element compositions and conducted 937 successful single analyses with laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) for trace element compositions on individual glass shards previously measured with the electron microprobe. In total, we were able to measure glass compositions for 254 samples. Of all the samples, 235 can be classified as tephra layers containing pyroclasts as the predominant component in their clast inventory between the 63 and 125 µm grain size fraction, often exceeding 90 vol%. The compositions of the Indian Ocean marine tephras range from basalt to rhyolite and from basaltic trachyandesite to trachyte and fall into the calc-alkaline, K-rich calc-alkaline, and shoshonitic magmatic series.
Published: 2023
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44. Volcanogenic aluminosilicate alteration drives formation of authigenic phases at the northern Hikurangi margin: Implications for subseafloor geochemical cycles

Author: M. Luo, W.-L. Hong, M.E. Torres, S. Kutterolf, K. Pank, J.L. Hopkins, E.A. Solomon, K.-L. Wang, and H.-Y. Lee
Subjects: Geochemistry and Petrology, Geology
Abstract: Alteration of volcanogenic aluminosilicates (VAs) in marine sediments is recognized as critical in regulating geochemical cycles and sustaining the oceanic deep biosphere, but rates of VA alteration and its associated authigenic mineral formation are not commonly reported. Here we present results on analyses of sediments and pore water recovered from the upper 150 mbsf of four sites drilled on the northern Hikurangi margin during IODP Expeditions 372 and 375. Petrographic analyses show that volcanogenic materials (glass shards, feldspar, volcanic lithoclasts) constitute important components (15–45 wt%) of the hemipelagic mud, and reveal ongoing glass alteration with accompanying authigenic phase formation. A reaction-transport model constrained by pore water Sr, 87Sr/86Sr, Ca, Mg, and Si was applied to simulate VA diagenetic reactions. Our model results yield VA alteration rates of 0.047–0.64 mmol Sr m−2 yr−1, with substantially higher values at Sites U1517 and U1520 that experienced rapid sediment emplacement. In addition, our simulations show that >99% of the dissolved Si generated by VA alteration is fixed in silica cement and authigenic clay, and that ∼50% of Ca incorporated in the authigenic carbonate is supplied by VA alteration. First-order estimates suggest that, in addition to authigenic carbonate precipitation, authigenic clay formation may represent an important sink for dissolved Mg. This study quantitatively examines the linkage between VA alteration and formation of authigenic phases, highlights its role in subsurface geochemical cycles, and indicates that slope instability may play an important role in promoting VA diagenesis.
Published: 2023
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45. The Boronated Scintillator Detector of the ISS-CREAM Experiment

Author: Y Amare, T Anderson, D J Angelaszek, N Anthony, K Cheryian, G H Choi, M Copley, S Coutu, L Derome, L Eraud, L Hagenau, J H Han, H G Huh, Y S Hwang, H J Hyun, S Im, H B Jeon, J A Jeon, S Jeong, S C Kang, H J Kim, K C Kim, M H Kim, H Y Lee, J Lee, M H Lee, J Liang, J T Link, L Lu, L Lutz, A Menchaca-Rocha, T Mernik, John W Mitchell, S I Mognet, S Morton, M Nester, S Nutter, O Ofoha, H Park, I H Park, J M Park, N Picot-Clemente, R Quinn, E S Seo, J R Smith, P Walpole, R P Weinmann, J Wu, and Y S Yoon
Subjects: Astrophysics
Abstract: The Cosmic Ray Energetics And Mass for the International Space Station (ISS-CREAM) instrument is a next-generation experiment for the direct detection and study of cosmic-ray nuclei and electrons. With a long exposure in low Earth orbit, the experiment will determine the particle fluxes and spectral details of cosmic-ray nuclei from hydrogen to iron, over an energy range of about 10(exp 12) eV to > 10(exp 15) eV, and of cosmic-ray electrons over an energy range of about 5x10(exp 10) eV to > 10(exp 13) eV. The instrument was deployed to the ISS in August 2017 on the SpaceX CRS-12 mission. We review the design, implementation and performance of one of the ISS-CREAM detector systems: a boron loaded scintillation detector used in discriminating electron-induced events from the much more abundant cosmic-ray nuclei.
Published: 2019
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46. EARLY NEOPROTEROZOIC CRUST FORMATON IN THE DZABKHAN MICROCONTINENT, CENTRAL ASIAN OROGENIC BELT

Author: V. P. Kovach, I. K. Kozakov, A. Kröner, E. B. Salnikova, K.-L. Wang, H.-Y. Lee, and S.-L. Chung
Subjects: Science
Abstract: The Dzabkhan microcontinent was defined by [Mossakovsky et al., 1994] as a cratonic terrane with an early Precambrian basement that combines highgrade metamorphic complexes of the Songino, Dzabkhan, Otgon, Baidarik, Ider and Jargalant Blocks. However, early Precambrian ages have so far only been recognized in the Baidarik and Ider blocks [Kozakov et al., 2007, 2011; Kröner et al., 2015].
Published: 2017
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47. MeCP2 SUMOylation rescues Mecp2-mutant-induced behavioural deficits in a mouse model of Rett syndrome

Author: Derek J. C. Tai, Yen C. Liu, Wei L. Hsu, Yun L. Ma, Sin J. Cheng, Shau Y. Liu, and Eminy H. Y. Lee
Subjects: Science
Abstract: Post-translational modifications of methyl-CpG-binding protein 2 (MeCP2) are important for its function and dysfunction in Rett syndrome. Here, Tai et al. show a functional interaction between MeCP2 SUMOylation and phosphorylation in rodent behavior and synaptic plasticity.
Published: 2016
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48. Timing and recurrence intervals for voluminous silicic eruptions from Amatitlán caldera (Guatemala)

Author: A. Cisneros de León, M. Danišík, J.C. Schindlbeck-Belo, S. Kutterolf, A.K. Schmitt, A. Freundt, J. Kling, K.-L. Wang, and H.-Y. Lee
Subjects: Archeology, Global and Planetary Change, Geology, Ecology, Evolution, Behavior and Systematics
Abstract: Defining a precise timeline for past eruptions from explosive volcanoes in continental arcs is imperative to forecast future hazards and mitigate volcanic disasters in these often densely populated regions. However, establishing reliable ages for Quaternary eruptions in the Central American Volcanic Arc has been challenging due to the common lack or alteration of suitable K-rich phases for 40Ar/39Ar geochronology, but also from their position in time beyond the reach of 14C dating. This especially holds for the active Amatitlán caldera in Guatemala, from which at least six explosive silicic eruptions have produced tephra blanketing neighboring regions that are today inhabited by millions of people. Zircon, a common datable accessory mineral in Amatitlán caldera magmas, is used here to retrieve eruption ages by applying the novel zircon double-dating method (ZDD) that integrates 238U–230Th disequilibrium dating and (U–Th)/He thermochronology. This approach yielded the first-ever radioisotopic ages of 24 ± 3 ka and 48 ± 6 ka (1σ), respectively, of two of Amatitlán caldera's most recent eruptions (J-tephra and E-tephra). Remarkably, both zircon crystallization and ZDD eruption ages for the older and voluminous T-tephra and L-tephra units significantly post-date existing plagioclase 40Ar/39Ar dates by ca. 26 and 70 kyr, respectively. The ZDD eruption age for T-tephra is 93 ± 4 ka, whereas zircon crystallization ages for L-tephra yield a maximum model eruption age of ca. 124 ka. The strong eruption age divergence between ZDD and plagioclase 40Ar/39Ar dating argues for the presence of inherited or xenocrystic plagioclase in Amatitlán caldera eruptive products. Statistical analysis based on the updated eruptive history suggests a recurrence interval of ca. 17 kyr, which is significantly shorter than previously estimated. The new age data, thus, suggest a more frequent eruptive activity of Amatitlán caldera than formerly thought and underscores the necessity to better understand the current underlying magmatic system and to constrain its past eruptive history more precisely.
Published: 2023
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49. Understanding the management of hypertension in Asia: results of a literature search

Author: A R Rahman, J D A Magno, J Cai, M Han, H Y Lee, T Nair, O Narayan, J Panyapat, H Van Minh, and R Khurana
Subjects: Cardiology and Cardiovascular Medicine
Abstract: Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Servier, France Background Hypertension poses a significant healthcare burden in Asia. Detection, treatment and control of hypertension are suboptimal, despite the existence of clear international guidelines and the availability of safe and effective treatments. Purpose To understand hypertension management in Asia, based on the analysis of national guidelines, treatment patterns and patient characteristics. Methods A PubMed search was performed using four search strings relating to 1) hypertension; 2) treatment/management/drug therapy; 3) guideline, consensus, real world evidence; and 4) Asian countries. The search was restricted to English language articles published since January 2008 to July 2022. Articles were filtered by relevance to the research question, study size, scope, methodology, and country/region to identify a target of 100 final references. Results The search yielded 2,436 articles, of which 92 were selected as being most relevant. Compared with Europeans, Asians appeared to have higher systolic blood pressure (BP), diastolic BP, and mean arterial pressure, with stronger association between BP and stroke. Rates of severe hypertension were also higher. Trends identified in the literature suggested that calcium channel blockers are the most common monotherapy used in Asian countries, with a high variability across the region. In the available publications focused on the studies with RAAS inhibitors, the majority of them compared the use of angiotensin receptor blockers as mono/combination therapy versus combination therapy with ACE inhibitors, calcium channel blockers or diuretics. Among treated patients, the observed control rates were only ~35–40% (~10% or less in the general population). There is a lack of focus on selecting the most appropriate treatment for each individual patient. Areas for improvement in delivering guideline-directed therapy for improved BP control also included facilitating access to health care and compliance with medication (including support mechanisms like community programmes, telemedicine, mobile phone apps and home BP monitoring), improving diet (reducing salt intake) and encouraging exercise. Conclusions Asian patients and European patients have different clinical profiles, with more severe hypertension in Asians. Rates of BP control across Asia are low. The management of hypertension requires a focused multimodal and supportive approach with implementation of public health measures, more effective screening initiatives and evidence-based goal-driven recommendations for appropriate pharmacotherapy augmented by lifestyle changes.
Published: 2023
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50. Lactic acid bacteria waste infusion as a source of attraction and oviposition stimulation of gravid female Aedes albopictus mosquitoes

Author: M M, Suria, P C, Yap, V L, Lov, S, AbuBakar, and H Y, Lee
Subjects: General Medicine
Abstract: Aedes albopictus poses a public health risk in tropical countries and temperate countries in recent decades due to its capability to transmit various human arboviruses including dengue, yellow fever, and chikungunya. Vector control is the key for preventing transmission of these pathogenic viruses. Improving the effectiveness of currently utilized collection methods, such as ovitraps, is important for best species abundance monitoring, assessment of the threat of arbovirus transmission, and optimizing control activities. Therefore, this study aimed to assess the potential use of lactic acid bacteria (LAB) waste as an infusion-baited ovitrap for Aedes collection. The performance of overnight tap water, grass hay infusion and LAB waste infusion were compared for their ability in attracting gravid female Ae. albopictus. In this study, the LAB waste infusion was substantially more alluring to Ae. albopictus mosquitoes than the two controls grass hay infusion and tap water.
Published: 2023

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