1,841 results on '"Flip"'
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2. The Alphabet Soup of Microscopy: An Introduction to Advanced Imaging Techniques. Part II: What the FLIP, FLAP, FRAP, FRET, and FLIM is Going On?
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Worden, Austin N
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FLUORESCENCE resonance energy transfer , *FLUORESCENCE microscopy , *MOLECULAR dynamics , *MOLECULAR interactions , *MICROSCOPY - Abstract
The use of fluorescence in imaging has been a pivotal factor in advancing our scientific understanding. As microscopy continues to evolve, the terminology used to describe these techniques becomes increasingly complex, often resulting in a bewildering array of acronyms that resemble alphabet soup. Among the most prominent acronyms are those associated with advanced fluorescence microscopy techniques: Fluorescence Loss in Photobleaching (FLIP), Fluorescence Localization after Photobleaching (FLAP), Fluorescence Recovery after Photobleaching (FRAP), Förster Resonance Energy Transfer (FRET), and Fluorescence Lifetime Imaging Microscopy (FLIM). Each of these methods provides invaluable insights into molecular dynamics and interactions within living cells and tissues. This article, Part 2 of the Alphabet Soup of Microscopy series, aims to clarify these widely used fluorescence microscopy techniques and to illuminate their contributions to our understanding of cellular processes. [ABSTRACT FROM AUTHOR]
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- 2024
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3. FLIP FOR PROMOTING ENGLISH LANGUAGE LEARNERS’ PRODUCTIVE SKILLS: CONNECTIVIST PRACTICES IN KAZAKHSTAN.
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Shelestova, Tatyana, Nabiyeva, Aizhan, Kalizhanova, Anna, Chuishbekov, Daniyar, and Turkenova, Saltanat
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WEB-based user interfaces ,TEACHER-student relationships ,ENGLISH language ,EXPERIMENTAL groups ,CONTROL groups - Abstract
This article reports the results of an explorative, quantitative study designed to investigate the pedagogical potential of Flip (formerly Flipgrid) as a connectivist and transmedia tool for developing English language learners’ productive skills to provide a basis for their continued improvement. The study suggests that the connectivist practice via Flip provides significant effect on improving secondary school students’ productive skills. A total of 39 students, divided randomly into one experimental group and one control group, participated in the study during the eight-week curriculum involving an English course. Participants in the experimental group (n = 19) used Flip as a learning tool, whereas the control group participants (n = 20) followed the same curriculum without Flip. Pre- and posttests were used to compare the participants’ speaking and writing productions before and after the project. These tests were evaluated based on a comparison of their mean scores by SPSS (Statistical Package for the Social Sciences) software. We used Questionnaires to analyze the positive and negative aspects of Flip. An independent samples t-test revealed that the experimental group outperformed the control group and showed the potential of regular Flip narrative-based tasks for developing English language learners’ productive skills (p ≤ 0.05 = 0.039). Thus, Flip can be used by teachers and learners to improve speaking and writing, and thus overcome the limitations on time, practice, and feedback inherent in classroom-based courses. [ABSTRACT FROM AUTHOR]
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- 2024
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4. Esophagogastric Junction Outflow Obstruction (EGJOO): A Manometric Phenomenon or Clinically Impactful Problem.
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Bach, Laura and Vela, Marcelo F.
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Purpose of Review: Esophagogastric junction outflow obstruction (EGJOO), defined manometrically by impaired esophagogastric junction relaxation (EGJ) with preserved peristalsis, can be artifactual, due to secondary etiologies (mechanical, medication-induced), or a true motility disorder. The purpose of this review is to go over the evolving approach to diagnosing and treating clinically relevant EGJOO. Recent Findings: Timed barium esophagram (TBE) and the functional lumen imaging probe (FLIP) are useful to identify clinically relevant EGJOO that merits lower esophageal sphincter (LES) directed therapies. There are no randomized controlled trials evaluating EJGOO treatment. Uncontrolled trials show effectiveness for pneumatic dilation and peroral endoscopic myotomy to treat confirmed EGJOO; Botox and Heller myotomy may also be considered but data for confirmed EGJOO is more limited. Summary: Diagnosis of clinically relevant idiopathic EGJOO requires symptoms, exclusion of mechanical and medication-related etiologies, and confirmation of EGJ obstruction by TBE or FLIP. Botox LES injection has limited durability, it can be used in patients who are not candidates for other treatments. PD and POEM are effective in confirmed EGJOO, Heller myotomy may also be considered but data for confirmed EGJOO is limited. Randomized controlled trials are needed to clarify optimal management of EGJOO. [ABSTRACT FROM AUTHOR]
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- 2024
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5. Theoretical differential fault attacks on FLIP and FiLIP.
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Méaux, Pierrick and Roy, Dibyendu
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In this article, we examine Differential Fault Attacks (DFA) targeting two stream ciphers, FLIP and FiLIP. We explore the fault model where an adversary flips a single bit of the key at an unknown position. Our analysis involves establishing complexity bounds for these attacks, contingent upon the cryptographic parameters of the Boolean functions employed as filters and the key size. Initially, we demonstrate how the concept of sensitivity enables the detection of the fault position using only a few keystream bits. This represents an enhancement over previous DFA methodologies applied to these ciphers. Subsequently, we leverage the properties of the filter's derivatives to execute attacks. This approach is universally applicable to any filter, and we delineate specific attack strategies for the two function families previously implemented in these ciphers. [ABSTRACT FROM AUTHOR]
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- 2024
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6. LEAP-ASIA-2019 Type-B Simulations Through FLIP
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Hyodo, Junichi, Ichii, Koji, Tobita, Tetsuo, editor, Ichii, Koji, editor, and Ueda, Kyohei, editor
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- 2024
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7. LEAP-ASIA-2019 Numerical Simulations Using a Strain Space Multiple Mechanism Model for a Liquefiable Sloping Ground
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Tanaka, Yoshikazu, Sahare, Anurag, Ueda, Kyohei, Yuyama, Waka, Iai, Susumu, Tobita, Tetsuo, editor, Ichii, Koji, editor, and Ueda, Kyohei, editor
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- 2024
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8. Meat Freshness State Prediction Using a Novel Fifteen Layered Deep Convolutional Neural Network
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Shyamala Devi, M., Arun Pandian, J., Umanandhini, D., Sakineti, Aayush Kumar, Jeyaraj, Rathinaraja, Kacprzyk, Janusz, Series Editor, Gomide, Fernando, Advisory Editor, Kaynak, Okyay, Advisory Editor, Liu, Derong, Advisory Editor, Pedrycz, Witold, Advisory Editor, Polycarpou, Marios M., Advisory Editor, Rudas, Imre J., Advisory Editor, Wang, Jun, Advisory Editor, Namasudra, Suyel, editor, Trivedi, Munesh Chandra, editor, Crespo, Ruben Gonzalez, editor, and Lorenz, Pascal, editor
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- 2024
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9. Exploring the role of FLIP and Itch in mechanisms of resistance to apoptosis
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Holloway, James, Evergren Mills, Emma, and Longley, Daniel
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Cell death ,Aapoptosis ,FLIP ,E3 Ligase - Abstract
A considerable number of cancers are inherently resistant to apoptosis demonstrating the need to develop novel strategies for combating this resistance. FLIP is the key negative regulator of the TRAIL-mediated apoptotic pathway and is frequently overexpressed in cancer. It elicits its anti-apoptotic function by preventing procaspase-8 homodimerization and auto-activation at the DISC. FLIP is a possible therapeutic target which has been difficult target due to structural similarities with procaspase-8. To progress the understanding of FLIP as a therapeutic targeted we investigated the regulation of FLIP through Itch-mediated ubiquitination and by disrupting its interaction with the pro-apoptotic FADD using newly developed inhibitors. Here we identify the E3 ubiquitin ligase Itch as a regulator of TRAIL sensitivity. OE33 Itch knockdown cells were more resistant to TRAIL-mediated apoptosis despite no observable change in the expression FLIP splice forms. We identified a novel role for Itch in regulating TRAIL-mediated apoptosis and chemotherapy. This study identified that levels of FLIP were a determining factor in mediating the induction of apoptosis in response to two novel FLIP inhibitors. These compounds induced procaspase-8 autoactivation which promoted downstream caspase signalling and induction of apoptosis. We observed that recruitment of FLIP to the death inducing signalling complex (DISC) at the plasma membrane was impaired by treatment with FLIP inhibitors thus facilitating the induction of apoptosis. Additionally, it identified that these inhibitors could enhance the activity of TRAIL in a FLIP-dependent manner in the HCT116 and U2OS cell lines. Procaspase-8 has a critical role in the function of these inhibitors. Its absence prevented DISC formation and induction of apoptosis in response to TRAIL. Knockout of its paralog, procaspase-10 was shown to enhance apoptotic signalling and DISC formation in response to izTRAIL and FLIP inhibition but could not compensate for the loss of procaspase-8. It was frequently observed that FLIP protein expression was negatively affected by the FLIP inhibitors. The expression of the anti-apoptotic protein MCL-1 was negatively affected by the FLIP inhibitors. Through two independent mechanisms this study demonstrated the importance of developing new approaches to overcome resistance to apoptosis in cancer. Further investigations are required to elucidate the resistance mechanisms governed by Itch and by FLIP in cancer cells. The FLIP inhibitors used in this study have promising in vitro effects which warrant further investigation in vivo.
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- 2023
10. Optimizing the Management Algorithm for Esophageal Dysphagia After Index Endoscopy: Cost-Effectiveness and Cost-Minimization Analysis.
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Shah, Eric D., Yadlapati, Rena, and Chan, Walter W.
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ESOPHAGEAL motility disorders , *DEGLUTITION disorders , *ESOPHAGEAL motility , *COST effectiveness , *ENDOSCOPY - Abstract
INTRODUCTION: Guidelines advise esophageal motility testing for dysphagia when structural disorders are ruled out, but cost concerns impede adoption. We evaluated cost-effective positioning of esophageal motility testing in the algorithm to evaluate esophageal dysphagia. METHODS: We developed a decision analytic model comparing 3 strategies: (i) esophageal manometry, (ii) screening impedance planimetry followed by esophageal manometry if needed, or (iii) nonalgorithmic usual care. Diagnostic test accuracy was adapted to expected rates of esophageal motility disorders in general gastroenterology populations. We modeled routine testing for all patients with nonstructural/ mechanical dysphagia compared with selective testing with strong suspicion for achalasia. Cost outcomes were defined on national commercial and Medicare datasets stratified on age and sex. Health outcomes were modeled on populations with achalasia. The time horizon was 1 year. RESULTS: Motility testing was preferred over nonalgorithmic usual care due to cost savings rather than health gains. To commercial insurers, routine esophageal manometry for nonstructural/mechanical dysphagia would be cost-saving below a reimbursed cost of $2,415. Screening impedance planimetry would be cost saving below a reimbursed cost of $1,130. The limit for reimbursed costs would be lower for patients older than 65 years to achieve cost savings mainly due to insurance. Sex did not significantly influence cost-effectiveness. Patients and insurers preferred routine screening impedance planimetry before manometry when the index of suspicion for achalasia was below 6%. DISCUSSION: Aligningwith practice guidelines, routine esophageal motility testing seems cost saving to patients and insurers compared with nonalgorithmic usual care to evaluate nonstructural/mechanical dysphagia. Choice of testing should be guided by index of suspicion. [ABSTRACT FROM AUTHOR]
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- 2024
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11. Esophageal Motility Disorders: Current Approach to Diagnostics and Therapeutics.
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Vaezi, Michael, Patel, Dhyanesh, and Yadlapati, Rena
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Absent Contractility ,Achalasia ,Barium Esophagram ,Distal Esophageal Spasm ,Esophageal Motility Disorders ,Esophagogastric Junction ,FLIP ,High-Resolution Manometry ,Hypercontractile Esophagus ,Ineffective Esophageal Motility ,Endoscopy ,Gastrointestinal ,Esophageal Achalasia ,Esophageal Motility Disorders ,Humans ,Manometry ,Quality of Life - Abstract
Dysphagia is a common symptom with significant impact on quality of life. Our diagnostic armamentarium was primarily limited to endoscopy and barium esophagram until the advent of manometric techniques in the 1970s, which provided the first reliable tool for assessment of esophageal motor function. Since that time, significant advances have been made over the last 3 decades in our understanding of various esophageal motility disorders due to improvement in diagnostics with high-resolution esophageal manometry. High-resolution esophageal manometry has improved the sensitivity for detecting achalasia and has also enhanced our understanding of spastic and hypomotility disorders of the esophageal body. In this review, we discuss the current approach to diagnosis and therapeutics of various esophageal motility disorders.
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- 2022
12. Impedance Planimetry: EndoFLIP
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Campbell, Michelle, Ujiki, Michael, Patel, Ankit D., editor, Aryaie, Amir, editor, Grams, Jayleen, editor, and Khaitan, Leena, editor
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- 2023
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13. On the Algebraic Immunity of Weightwise Perfectly Balanced Functions
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Gini, Agnese, Méaux, Pierrick, Goos, Gerhard, Founding Editor, Hartmanis, Juris, Founding Editor, Bertino, Elisa, Editorial Board Member, Gao, Wen, Editorial Board Member, Steffen, Bernhard, Editorial Board Member, Yung, Moti, Editorial Board Member, Aly, Abdelrahaman, editor, and Tibouchi, Mehdi, editor
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- 2023
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14. Peroral Endoscopic Myotomy (POEM)
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Snyder, Matthew M., Hungness, Eric S., Kroh, Matthew, editor, Docimo Jr., Salvatore, editor, El Djouzi, Sofiane, editor, Shada, Amber, editor, and Reavis, Kevin M., editor
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- 2023
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15. Use of Fourier phase characteristics and effective stress analyses for post-earthquake ground motion estimation: application to ESG6 blind prediction steps 2&3 dataset and JMA accelerometric data
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Atsushi Nozu
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Site effect ,Fourier phase spectrum ,Soil nonlinearity ,Effective stress analysis ,FLIP ,Geography. Anthropology. Recreation ,Geodesy ,QB275-343 ,Geology ,QE1-996.5 - Abstract
Abstract After the occurrence of a large earthquake, engineering seismologists are often requested to estimate strong ground motions at a site where strong motion data were not obtained. The goal of this study was to test the ability of a class of methods that uses Fourier phase characteristics for the post-earthquake ground motion estimation, making use of the precious opportunity provide by the ESG6 Blind Prediction Steps 2&3. It was also part of the goal of this study to test the performance of the effective stress analyses to account for soil nonlinearity. In addition to the dataset provided by the organizer of the blind prediction, the author used additional accelerometric data from a nearby JMA site. To simulate ground motions for an M5.9 earthquake at the target site “KUMA”, the Fourier amplitude spectrum was estimated from the spectral ratio between KUMA and the nearby JMA site. The Fourier phase spectrum was approximated by the spectrum of another event at KUMA. Comparison between the estimated and recorded ground motions after the blind prediction revealed that the estimated ground motions were fairly consistent with the observed ground motions, indicating the effectiveness of the method when the rupture process of the target event is simple and the soil nonlinearity at the target site is not significant. To simulate ground motions at KUMA for the M6.5 foreshock and the M7.3 mainshock of the 2016 Kumamoto earthquake sequence, the author conducted effective stress analyses using a program called “FLIP” to account for soil nonlinearity. Comparison between the estimated and recorded ground motions after the blind prediction indicated that the low-frequency components were overestimated and the high-frequency components were underestimated. The strong soil nonlinearity considered in the effective stress analyses was the main cause of the discrepancy. One explanation for this result could be that the nonlinear soil behavior at KUMA during the foreshock and the mainshock was not a strong one. Another explanation could be that the effect of soil nonlinearity was already included in the records at JMA and the effect of soil nonlinearity was double counted in the results submitted by the author. Graphical Abstract
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- 2023
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16. Supporting Speaking Skills Development in EFL Teacher-Training Students via Flip During the COVID-19 Pandemic.
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Contreras Soto, Yasmina, Oportus Torres, René, Sanhueza-Campos, Cristian, and Maluenda Albornoz, Jorge
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COVID-19 pandemic ,ENGLISH as a foreign language ,TRAINING of English teachers ,ACADEMIC achievement ,UNIVERSITIES & colleges - Abstract
This study is set in EFL teacher training during the COVID -19 pandemic. The goal of this research study was to examine students' perceptions of the development of their oral abilities by means of weekly Flip video recordings. An action research design was carried out for EFL teacher-training students from a Chilean university. Synchronous English language sessions focusing on oral production were aided by asynchronous practice on the Flip platform. Content analysis was conducted to examine the students' perceptions of the use of Flip to facilitate the development of speaking skills. Cooccurring categories were identified, and related networks were produced to identify relevant nodes. Findings revealed favorable perceptions in both the linguistic and socioaffective aspects of learners' oral performance resulting from the weekly recordings. It was concluded that the use of Flip promoted the students' oral production by heightened positive socioaffective perceptions over the course of one academic semester during the time of COVID-19. [ABSTRACT FROM AUTHOR]
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- 2023
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17. Delineating mechanisms which underlie differential cell fates induced by p53 activation and HDAC inhibition in colorectal cancer
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Lees, Andrea, McDade, Simon, and Longley, Daniel
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616.99 ,p53 ,Cell death ,Nutlin-3A ,Entinostat ,Apoptosis ,FLIP ,HDAC inhibitors - Abstract
The tumour suppressor p53 is the most frequently mutated gene in human cancer with loss or suppression of wild-type function thought to be a prerequisite for the development of most malignancies. In colorectal cancer (CRC), approximately 50% of tumours harbour mutations in the TP53 gene, whilst the remaining wild-type tumours suppress or circumvent p53 activation via non-mutational mechanisms. This includes dysregulation of the p14ARF/MDM2 axis which constitutes the major mechanism for inducing p53 stabilisation within the cell. Strategies aimed at reactivating latent wild-type p53 in such tumours therefore hold enormous clinical potential. This led to the development of small molecule inhibitors of the E3 ubiquitin ligase, MDM2, which normally targets p53 for degradation and disrupts its transcription factor activity. Blocking this negative MDM2-p53 interaction results in rapid stabilisation of p53 protein, however, this most often leads to the activation of p53-induced cell cycle arrest rather than cell death. Understanding the mechanisms which are responsible for this decision making process are therefore of great importance in order to utilise these compounds and augment the efficacy of other therapeutic agents that activate p53. Recent work in our lab has demonstrated that combination of direct (MDM2 inhibition) or indirect (DNA-damaging chemotherapy) p53 activation with inhibitors of nuclear Class-I Histone deacetylases (HDACi) is effective in enhancing p53- dependent apoptotic cell death in multiple models of CRC. Interestingly, despite a notable switch in phenotype from cell cycle arrest to cell death, few changes in the mRNA and protein expression of pro-apoptotic p53 targets were observed following combined treatment with the MDM2 inhibitor, Nutlin-3A, and the Class I specific HDACi, Entinostat, when compared to Nutlin-3A treatment alone. Indeed, the addition of Entinostat was instead found to decrease the expression of p53 induced anti-apoptotic proteins which most notably included the only known pseudo-caspase and cell death regulatory protein, FLIPL. The work presented in this thesis builds upon these previous observations and delves into the complex mechanisms and pathways responsible for the synergistic induction of cell death following combined MDM2- and HDAC-inhibition in p53 wild-type models of CRC. Using both functional genomics and molecular techniques, this work identifies FLIPL as a direct, p53-induced transcriptional target which is potently upregulated by Nutlin-3A and suppressed by Entinostat. Importantly, both pharmacological and mutational inhibition of the NFκB pathway reveal that the Nutlin-3A-induced upregulation of FLIPL occurs independently of its canonical regulation by NFκB, further supporting the p53-dependent nature of this response. Phenotypic analyses conducted by Annexin V/PI flow cytometry reveal that whilst treatment with Nutlin-3A or Entinostat alone fail to induce cell death, combining these agents significantly increases the induction of apoptotic cell death in a p53- dependent manner. In order to delineate the role of Entinostat mediated FLIPL downregulation in the cell death resulting from the combined Nutlin-3A/Entinostat treatment, siRNA-mediated FLIPL depletion was used to successfully phenocopy this result. Subsequently, further mechanistic analyses demonstrated that p53-mediated FLIPL upregulation blocks the induction of apoptosis by inhibiting caspase-8 activation at a TRAIL-R2/DR5 death inducing signalling complex. Notably, the activation of this p53-induced complex occurs independently of canonical TRAIL ligand binding. In addition to the early induction of caspase-8 dependent apoptotic cell death, this work reveals that depleting FLIPL in combination with p53 activation can also result in the induction of caspase-8 independent cell death at later timepoints. Herein, the p53 transcriptional target and caspase-8 paralog, caspase-10, is demonstrated to compensate for the loss of caspase-8 in order to induce apoptosis, albeit to a lesser extent than in caspase-8 proficient cells. Moreover, FLIPL is also revealed to modulate the expression of p53 transcriptional targets such that in the absence of both caspase-8 and -10 cell death can still proceed. Depleting FLIPL is shown to suppress the p53-induced expression of the cell-cycle inhibitor, p21, whilst simultaneously enhancing the p53-induced expression of the pro-apoptotic protein, PUMA. Indeed, this upregulation of PUMA significantly contributes to the cell death induced by FLIPL depletion and p53 activation at later timepoints. Thus, the results presented in this thesis identify novel, clinically-relevant biology in which FLIPL acts to determine cell fate following p53 activation. Therapeutically targeting FLIPL with Entinostat therefore represents a viable means of overcoming FLIPL-mediated resistance to MDM2-inhibitors in tumours retaining wild-type p53.
- Published
- 2021
18. Pre-clinical evaluation of inhibitors of apoptosis protein (IAP) antagonists in colorectal cancer
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Stott, Katie, Longley, Daniel, Hallsworth, John, and Bengoechea, Jose
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616.99 ,Colorectal cancer ,Inhibitor of Apoptosis Proteins ,Fusobacterium nucleatum ,Entinostat ,FLIP ,Apoptosis - Abstract
Colorectal cancer (CRC) is a leading cause of cancer-related death and the third most common type of cancer worldwide. The five-year survival rate strongly correlates with the stage of the disease at initial diagnosis, falling from well over 90% at Stage I to less than 10% when diagnosed at Stage IV. Drug resistance is a major limitation to current treatment options for advanced CRC. Consequently, there is an unmet clinical need for novel therapeutic agents for treating patients with CRC in the advanced disease setting. CRC is frequently associated with a pro-inflammatory tumour microenvironment in which TNFα signalling plays an important role. Inhibitor of apoptosis proteins (IAPs) are capable of converting TNFα signalling from a pro-apoptotic to a pro-survival and pro-inflammatory signal. Overexpression of IAPs is associated with chemoresistance and poor prognosis in CRC. Consequently, IAPs are an attractive target for therapeutic intervention, and IAP antagonists, such as ASTX660, have recently been developed in order to exploit their pro-survival mechanisms. When TNFα binds to its receptor TNFR1 in the presence of an IAP antagonist, it leads to the formation of a cytoplasmic death-inducing complex consisting of RIPK1, FADD and procaspase-8. Procaspase-8 undergoes homodimerization within this complex and subsequently activates effector caspases-3 and -7 to promote apoptosis. FLIP, a pseudo-caspase, can also bind to FADD and inhibit homodimerization of procaspase-8, subsequently inhibiting apoptosis. In vitro results indicated that the CRC cell line models investigated herein harboured intrinsic resistance to IAP antagonist-mediated cell death, even in the presence of recombinant TNFα. Further investigation using siRNA-mediated silencing techniques, revealed FLIP is a major mediator of this resistance mechanism. Moreover, Entinostat, a clinically relevant Class I HDAC inhibitor, was found to downregulate FLIP expression and sensitise CRC cell line models to ASTX660. Through the use of procaspase-8 and procaspase-10 CRISPR-Cas9 knockout cell lines, the enhanced cell death observed was determined to be dependent on caspase-8, but not on its paralog, caspase-10. Furthermore, FLIP-mediated resistance, to ASTX660 and TNFα, was also overcome through the use of a novel small molecule FLIP inhibitor that targets the FLIP:FADD protein-protein interaction (PPI). Clinical approval of IAP antagonists is not only hampered by intrinsic resistance, but also by a lack of clinical biomarkers to stratify patients who would respond well to this treatment. Herein, the potential of using the presence of a Fusobacterium nucleatum infection as a predictive biomarker for clinical positioning of these agents was investigated. F. nucleatum infection was shown to promote an upregulation of CIAP2 and TNFα in pre-clinical models and this correlated with observations made in clinical samples. Interestingly, there was evidence to suggest that FLIP expression was downregulated by F. nucleatum infection. Importantly, co-culture of F. nucleatum infected monocytic cells significantly enhanced the efficacy of IAP antagonism in a manner dependent on bacterial induction of TNFα secretion in the immune cells. Collectively, this work suggests that the presence of F. nucleatum bacteria in colorectal tumours promotes a tumour microenvironment rich in TNFα levels and may 'prime' tumours with elevated CIAP2 and lower FLIP expression to become sensitive to IAP antagonists. Overall, the work presented in this thesis indicates that IAP antagonists may be most effective in pro-inflammatory, TNFα-rich CRC, but only if combined with an agent capable of overcoming FLIP-mediated resistance. Furthermore, the data presented suggest that the presence of F. nucleatum has the potential to be utilised as a predictive biomarker to identify patients who would benefit from IAP antagonistic therapy.
- Published
- 2021
19. Development of novel antibody-targeted nanoparticle strategies for treatment of pancreatic cancer
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Johnston, Michael, Longley, Daniel, and Scott, Christopher
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Nanoparticles ,Nanomedicine ,FLIP ,Death Receptor 5 ,Camptothecin - Abstract
Despite major advancements in the treatment of many cancers, pancreatic cancer has one of the poorest survival rates of all, with a ten-year survival of less than 1%. One experimental clinical approach to treat pancreatic cancer had involved targeting an apoptosis pathway, the TNF-related apoptosisinducing ligand (TRAIL) receptor 2/ death receptor-5 (DR5) pathway using the monoclonal antibody conatumumab (AMG 655). However, the results of these clinical trials proved disappointing with no survival advantage being observed. Subsequent literature has suggested that this was most likely due to inadequate receptor clustering and consequent lack of tumour cell apoptosis. In view of this, this thesis attempted to address the lack of efficacy with conatumumab through developing a nanoparticle-based approach armed with an entrapped chemotherapeutic and driving receptor clustering by decorating the nanoparticles with conatumumab. The initial work in this thesis sought to test various nanoformulation approaches with the aim of characterising size and manufacturability, entrapment, ligand conjugation and in vitro efficacy. Initially, a formulation method was developed to generate nanoparticles of smaller size than traditionally formulated from the single emulsion method. A hybrid method combining salting out and single emulsion nanoparticle formulation techniques proved better than the single emulsion method in reducing particle diameter. However, with this method entrapment proved inadequate achieving only 1% efficiency. Entrapment of two established chemotherapy drugs was attempted including gemcitabine and camptothecin, and an experimental FLIP inhibitor 3642. Given its hydrophilic nature, a derivative of the double emulsion method was employed to entrap gemcitabine. But, while this showed in vitro efficacy, concerns regarding entrapment and ligand conjugation quantification precluded further development. A derivative of the single emulsion method was used to entrap 3642 and in vitro efficacy was achieved, this was not taken forward due to restrictions with freedom-to-operate and a lack of drug substance. The topoisomerase 1 inhibitor camptothecin was chosen as the payload of choice in the nanoparticle candidate going forward. Camptothecin had a number of advantages 1) it showed favourable entrapment using the single emulsion method given its hydrophobic nature, 2) it is fluorescent, meaning entrapment could be quantified with ease, 3) the much less potent topoisomerase 1 inhibitor, irinotecan is currently used in pancreatic cancer treatment as part of the FOLFIRINOX regimen. To improve antibody conjugation a novel N-hydroxysuccinamide endcapped polymer was employed to circumvent the need for in situ EDC functionalisation of carboxyl groups. This resulted in improved AMG 655 conjugation efficiency versus previously observed methods with fewer manufacturing steps required. In chapter 4 the functional potency of the nanoparticle was investigated using a number of pancreatic tumour cell lines. Initially the level of DR5 receptor expression was determined both by flow cytometry and by Western blot. Variable levels of DR5 expression were observed ranging from 15% in PANC1 to 75% in AsPC-1 cell lines. Conjugation of AMG 655 to the nanoparticle surface (in the absence of drug) rendered it capable of reducing cell viability in all 4 cell line models treated. Notably this reduction did not correlate with DR5 surface expression but was consistent with observations in the literature. The reduction of viability was promising and the addition camptothecin improved this potency. The combined effect of conjugated AMG 655 and entrapped camptothecin reduced cell viability in a synergistic manner. In Chapter 4 the role of inhibitors of apoptosis FLICE-inhibitory protein (FLIP) and inhibitor of apoptosis protein (XIAP) were explored. It was clear that camptothecin downregulated FLIP and XIAP in a dose dependent manner. To gauge whether this downregulation was a potential explanation for the synergy observed or an off-target effect, siRNA knockdown of FLIP splice forms and XIAP was employed to simulate the downregulation observed from camptothecin. This revealed that FLIP downregulation contributed significantly by enhancing the potency of conjugated AMG 655. Furthermore, CRISPR (clustered regularly interspaced short palindromic repeats) targeting of FADD (Fas Associated Via Death Domain) and caspase 8 revealed that the synergy observed using this formulation was DR5 pathway-dependent. Given the success of testing in vitro, in vivo efficacy of the formulation was next investigated. Initially, cell line xenografts of MIA PaCa-2 and PANC-1 were employed and the results revealed that, when injected intravenously, the formulation reached the tumour site in quantities sufficient to block tumour growth. Patient-derived xenograft (PDX) models were next explored as a means to more accurately simulate the pancreatic cancer environment as these models form stroma and have not been immortalised. Unfortunately, no efficacy was observed in either PDX model. This may be due to the stromal barrier, a lack of DR5 expression or slower PDX growth compared to the cell line xenograft - requiring an altered dosage regimen. Moreover, the lack of histology or access to tumour samples that could be analysed for drug infiltration or apoptotic markers prevented appropriate evaluation of these models. In summary, a lead nanoparticle candidate was developed exhibiting good manufacturability and cytotoxicity. The potent cytotoxicity observed was synergistic, associated with FLIP downregulation and was DR5 pathwaydependent. This formulation exhibited promising in vivo efficacy in cell line xenografts. Despite the lack of efficacy observed in the PDX models CPT DR5 NP has demonstrated potent cell kill and in vivo efficacy and given the lack of available therapeutic options in the clinic this formulation could be optimised for further evaluation in both in vitro and in vivo models.
- Published
- 2020
20. Leveraging Flip , a Video Discussion Platform, to Support the Needs of International ESL Pre-Service Teachers.
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Chen, Weina L. and Wong, Kevin M.
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FOREIGN students , *ENGLISH as a foreign language , *STUDENT teachers - Abstract
International students, particularly international English as a Second Language (ESL) students who come to the United States with relatively lower levels of English oral language proficiency, are often reluctant to participate in academic discussions. In a graduate-level TESOL program with a majority of international ESL students, a video recording, sharing, and discussion platform, Flip, was utilized in the program's teaching innovation. Flip is widely adopted by educators of all grade levels worldwide, as it enables educators to create a less formal online space to meet the holistic needs of international ESL students, including both academic and social needs. The article explains the teaching context of the practice, four stages of course integration with Flip, reasons for the integration, reflections, and future pedagogical directions. Incorporating Flip in this program promotes linguistic benefits, teacher identity and skill development, a community of belonging, and increased equity in assessment. Practical pedagogical considerations are also provided at the end of the article. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
21. Use of Fourier phase characteristics and effective stress analyses for post-earthquake ground motion estimation: application to ESG6 blind prediction steps 2&3 dataset and JMA accelerometric data.
- Author
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Nozu, Atsushi
- Subjects
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GROUND motion , *STRAINS & stresses (Mechanics) , *EARTHQUAKE resistant design , *EARTHQUAKES , *SEISMOLOGISTS , *FORECASTING - Abstract
After the occurrence of a large earthquake, engineering seismologists are often requested to estimate strong ground motions at a site where strong motion data were not obtained. The goal of this study was to test the ability of a class of methods that uses Fourier phase characteristics for the post-earthquake ground motion estimation, making use of the precious opportunity provide by the ESG6 Blind Prediction Steps 2&3. It was also part of the goal of this study to test the performance of the effective stress analyses to account for soil nonlinearity. In addition to the dataset provided by the organizer of the blind prediction, the author used additional accelerometric data from a nearby JMA site. To simulate ground motions for an M5.9 earthquake at the target site "KUMA", the Fourier amplitude spectrum was estimated from the spectral ratio between KUMA and the nearby JMA site. The Fourier phase spectrum was approximated by the spectrum of another event at KUMA. Comparison between the estimated and recorded ground motions after the blind prediction revealed that the estimated ground motions were fairly consistent with the observed ground motions, indicating the effectiveness of the method when the rupture process of the target event is simple and the soil nonlinearity at the target site is not significant. To simulate ground motions at KUMA for the M6.5 foreshock and the M7.3 mainshock of the 2016 Kumamoto earthquake sequence, the author conducted effective stress analyses using a program called "FLIP" to account for soil nonlinearity. Comparison between the estimated and recorded ground motions after the blind prediction indicated that the low-frequency components were overestimated and the high-frequency components were underestimated. The strong soil nonlinearity considered in the effective stress analyses was the main cause of the discrepancy. One explanation for this result could be that the nonlinear soil behavior at KUMA during the foreshock and the mainshock was not a strong one. Another explanation could be that the effect of soil nonlinearity was already included in the records at JMA and the effect of soil nonlinearity was double counted in the results submitted by the author. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
22. Affine particle in cell method for MAC grids and fluid simulation
- Author
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Ding, Ounan, Shinar, Tamar, and Schroeder, Craig
- Subjects
APIC ,PIC ,FLIP ,MPM ,Hybrid Lagrangian/Eulerian ,Computational fluid dynamics ,Mathematical Sciences ,Physical Sciences ,Engineering ,Applied Mathematics - Published
- 2020
23. Comparing Religions in Public: Rural America, Evangelicals, and the Prophetic Function of the Humanities
- Author
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Kripal, Jeffrey J., Pinn, Anthony B., Series Editor, Manemann, Jürgen, Series Editor, and Hart, William David, editor
- Published
- 2022
- Full Text
- View/download PDF
24. Utilizing Flip® as a platform to facilitate a group project in a socially distanced environment.
- Author
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Waghel, Rashi C., Wilson, Jennifer A., and Dinkins, Melissa M.
- Abstract
This study evaluated the perceived impact of using Flip (Microsoft Corp.) to facilitate a group project in a socially distanced environment. Student groups were assigned a self-care scenario, and students independently traveled to local pharmacies to identify a pertinent nonprescription product. Students individually recorded a review of the product using Flip. Subsequently, students reviewed and replied to group member videos to compare products. Students worked as a group to develop consensus regarding the most appropriate product recommendation for their scenario. At semester end, students completed a questionnaire about their experiences using Flip for the project. Sixty-eight students (91%) completed the perceptions questionnaire at course conclusion. Students found Flip enjoyable (68%) and easy to use (74%). The majority of students (82%) viewed all of their group members' Flip videos, and most (88%) agreed or strongly agreed Flip facilitated group work in a socially distanced environment. Students overall perceived Flip as enjoyable and easy to use. Though utilization of Flip was initially due social distancing requirements, the positive student feedback encouraged continued use of this platform asynchronously. Flip provides a unique mechanism for facilitating group projects in multiple different environments. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
25. 斜撑离合器常见失效模式及解决措施.
- Author
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李继锋, 李泽强, 席仕平, 杨立光, and 刘兢
- Subjects
FAILURE mode & effects analysis ,TORQUE ,IMPACT loads ,FLIP chip technology ,PROBABILITY theory ,WEDGES - Abstract
Copyright of Bearing is the property of Bearing Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2023
- Full Text
- View/download PDF
26. Student Perceptions on the Use of Flip in Higher Education: Learning Strategies and Classroom Community.
- Author
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Wissman, Kathryn T.
- Subjects
HIGHER education research ,FLIPPED classrooms ,CLASSROOM environment ,EDUCATIONAL support ,DISTANCE education - Abstract
Finding creative and effective ways to support student experiences and student learning in the classroom is an important goal for instructors, especially as remote and hybrid formats become more common and new, educational technologies are recommended. The current work involved the creation and implementation of a curricular innovation using Flip to encourage the use of evidence-based learning strategies and promote a sense of community in a college classroom. A survey was developed and administered as extra credit in a large Introduction to Psychology class in Spring 2021, with questions focused on examining student perceptions of using Flip in the classroom. Results revealed that students enjoyed using Flip for assignments, believed that Flip assignments helped their learning of class content, and recommended the instructor keeping using Flip in future semesters. The current work highlights the versatility and benefit of using Flip as an instructional tool in the classroom. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
27. Design and Motion Planning of a Metamorphic Flipping Robot.
- Author
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Guan, Yuntao, Zhuang, Zheming, Zhang, Chunsong, Tang, Zhao, Zhang, Ze, and Dai, Jian S.
- Subjects
ROBOT motion ,ROBOTS - Abstract
With the advantages of high flexibility, strong adaptability, etc., the legged robot can help humans to complete numerous complicated tasks. In this paper, a kind of reconfigurable legged robot with a flexible waist was proposed. Compared with the common robots with a rigid trunk, the proposed robot can twist its waist flexibly. Through analysis, it is found that the flexible waist can improve the trunk workspace, foot endpoints' workspace and static stability margin of the robot, and further enhance the motion performance of the robot. Meanwhile, by imitating the creatures in nature, the motion gait planning of the robot was provided. Additionally, the proposed robot has excellent reconfigurable characteristics, and can flexibly transform among three forms to adapt to different working environments and accomplish different tasks. Further, after capsizing, the robot can complete the motion of turning over more easily. In this paper, the reconfiguration posture and the motion of turning over of the robot were planned in detail, and finally verified by ADAMS simulation. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
28. Combinatorial flip actions and Gelfand pairs for affine Weyl groups.
- Author
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Adin, Ron M., Hegedüs, Pál, and Roichman, Yuval
- Subjects
- *
WEYL groups , *TRIANGULATION - Abstract
Several combinatorial actions of the affine Weyl group of type C ˜ n on triangulations, trees, words and permutations are compared. Addressing a question of David Vogan, we show that, modulo a natural involution, these permutation representations are multiplicity-free. The proof uses a general construction of Gelfand subgroups in the affine Weyl groups of types C ˜ n and B ˜ n. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
29. A quadri-fluorescence SARS-CoV-2 pseudovirus system for efficient antigenic characterization of multiple circulating variants.
- Author
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Chen J, Huang Z, Xiao J, Du S, Bu Q, Guo H, Ye J, Chen S, Gao J, Li Z, Lan M, Wang S, Zhang T, Zhang J, Wu Y, Zhang Y, Xia N, Yuan Q, and Cheng T
- Subjects
- Animals, Humans, Cricetinae, Spike Glycoprotein, Coronavirus immunology, Spike Glycoprotein, Coronavirus genetics, COVID-19 Vaccines immunology, COVID-19 Vaccines administration & dosage, Neutralization Tests methods, Fluorescence, HEK293 Cells, Antigens, Viral immunology, Antibodies, Monoclonal immunology, Mesocricetus, SARS-CoV-2 immunology, SARS-CoV-2 genetics, COVID-19 immunology, COVID-19 virology, Antibodies, Neutralizing immunology, Antibodies, Neutralizing blood, Antibodies, Viral blood, Antibodies, Viral immunology
- Abstract
The ongoing co-circulation of multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains necessitates advanced methods such as high-throughput multiplex pseudovirus systems for evaluating immune responses to different variants, crucial for developing updated vaccines and neutralizing antibodies (nAbs). We have developed a quadri-fluorescence (qFluo) pseudovirus platform by four fluorescent reporters with different spectra, allowing simultaneous measurement of the nAbs against four variants in a single test. qFluo shows high concordance with the classical single-reporter assay when testing monoclonal antibodies and human plasma. Utilizing qFluo, we assessed the immunogenicities of the spike of BA.5, BQ.1.1, XBB.1.5, and CH.1.1 in hamsters. An analysis of cross-neutralization against 51 variants demonstrated superior protective immunity from XBB.1.5, especially against prevalent strains such as "FLip" and JN.1, compared to BA.5. Our finding partially fills the knowledge gap concerning the immunogenic efficacy of the XBB.1.5 vaccine against current dominant variants, being instrumental in vaccine-strain decisions and insight into the evolutionary path of SARS-CoV-2., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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- View/download PDF
30. Restoring TRAILR2/DR5-Mediated Activation of Apoptosis upon Endoplasmic Reticulum Stress as a Therapeutic Strategy in Cancer.
- Author
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Mora-Molina, Rocío and López-Rivas, Abelardo
- Subjects
- *
CELLULAR control mechanisms , *ENDOPLASMIC reticulum , *CELL death , *UNFOLDED protein response , *CELL physiology , *TUMOR necrosis factors - Abstract
The uncontrolled proliferation of malignant cells in growing tumors results in the generation of different stressors in the tumor microenvironment, such as nutrient shortage, hypoxia and acidosis, among others, that disrupt endoplasmic reticulum (ER) homeostasis and may lead to ER stress. As a response to ER stress, both normal and tumor cells launch a set of signaling pathways known as the unfolded protein response (UPR) to restore ER proteostasis and maintain cell viability and function. However, under sustained ER stress, an apoptotic cell death process can be induced and this has been the subject of different review articles, although the role of the TRAIL-R2/DR5-activated extrinsic pathway of apoptosis has not yet been thoroughly summarized. In this Review, we provide an updated overview of the molecular mechanisms regulating cell fate decisions in tumor cells undergoing ER stress and discuss the role of the tumor necrosis factor (TNF)-related apoptosis-inducing ligand receptor 2 (TRAIL-R2/DR5) in the final outcome of UPR signaling. Particularly, we focus on the mechanisms controlling cellular FLICE-like inhibitory protein (FLIP) levels in tumor cells undergoing ER stress, which may represent a potential target for therapeutic intervention in cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
31. Spatiotemporal Pattern Formation in a Discrete Toxic-Phytoplankton–Zooplankton Model with Cross-Diffusion and Weak Allee Effect.
- Author
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Zhang, Feifan, Tian, Hao, Zhao, Hongfan, Zhang, Xinran, and Shi, Qiyu
- Subjects
- *
ALLEE effect , *BIFURCATION diagrams - Abstract
Phytoplankton patterns have been observed widely in aquatic systems. Although pattern formation has been investigated based on many PDEs, discrete models on aquatic systems can provide more complex dynamics. A discrete toxic-phytoplankton–zooplankton model is studied in this paper, with the consideration of Allee effect and cross-diffusion. Focusing on Allee effect coefficient, flip and Neimark–Sacker bifurcation analyses are carried out. And focusing on cross-diffusion coefficient, Turing bifurcation analyses are carried out. Parameter conditions and bifurcation diagram of these bifurcations are obtained correspondingly. Numerical simulations are then performed which are consistent with results of theoretical analysis. Irregular patterns can be formed by flip bifurcation. Spirals can be formed by Neimark–Sacker bifurcation. Spots and stripes can be formed by Turing bifurcation. When Turing and flip, or Turing and Neimark–Sacker bifurcations both occur, special patterns can be obtained. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
32. Crural closure, not fundoplication, results in a significant decrease in lower esophageal sphincter distensibility.
- Author
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Attaar, Mikhail, Su, Bailey, Wong, Harry, Callahan, Zachary, Kuchta, Kristine, Stearns, Stephen, Linn, John G., Denham, Woody, Haggerty, Stephen P., and Ujiki, Michael B.
- Subjects
- *
FUNDOPLICATION , *HIATAL hernia , *HERNIA surgery , *SPHINCTERS , *HERNIA , *ESOPHAGOGASTRIC junction , *PNEUMOPERITONEUM - Abstract
Introduction: The esophagogastric junction (EGJ) is a complex anti-reflux barrier whose integrity relies on both the intrinsic lower esophageal sphincter (LES) and extrinsic crural diaphragm. During hiatal hernia repair, it is unclear whether the crural closure or the fundoplication is more important to restore the anti-reflux barrier. The objective of this study is to analyze changes in LES minimum diameter (Dmin) and distensibility index (DI) using the endoluminal functional lumen imaging probe (FLIP) during hiatal hernia repair. Methods: Following implementation of a standardized operative FLIP protocol, all data were collected prospectively and entered into a quality database. This data were reviewed retrospectively for all patients undergoing hiatal hernia repair. FLIP measurements were collected prior to hernia dissection, after hernia reduction, after cruroplasty, and after fundoplication. Additionally, subjective assessment of the tightness of crural closure was rated by the primary surgeon on a scale of 1 to 5, 1 being the loosest and 5 being the tightest. Results: Between August 2018 and February 2020, 97 hiatal hernia repairs were performed by a single surgeon. FLIP measurements collected using a 40-mL volume fill without pneumoperitoneum demonstrated a significant decrease in LES Dmin (13.84 ± 2.59 to 10.27 ± 2.09) and DI (6.81 ± 3.03 to 2.85 ± 1.23 mm2/mmHg) after crural closure (both p < 0.0001). Following fundoplication, there was a small, but also statistically significant, increase in both Dmin and DI (both p < 0.0001). Additionally, subjective assessment of crural tightness after cruroplasty correlated well with DI (r = − 0.466, p < 0.001) and all patients with a crural tightness rating ≥ 4.5 (N = 13) had a DI < 2.0 mm2/mmHg. Conclusion: Cruroplasty results in a significant decrease in LES distensibility and may be more important than fundoplication in restoring EGJ competency. Additionally, subjective estimation of crural tightness correlates well with objective FLIP evaluation, suggesting surgeon assessment of cruroplasty is reliable. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
33. A note on a flip-connected class of generalized domino tilings of the box [0,2]n.
- Author
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Kisielewicz, Andrzej P.
- Subjects
- *
TILING (Mathematics) , *FAMILIES - Abstract
Let n , d ∈ N and n > d. An (n − d) -domino is a box I 1 × ⋯ × I n such that I j ∈ { [ 0 , 1 ] , [ 1 , 2 ] } for all j ∈ N ⊂ [ n ] with | N | = d and I i = [ 0 , 2 ] for every i ∈ [ n ] ∖ N. If A and B are two (n − d) -dominoes such that A ∪ B is an (n − (d − 1)) -domino, then A , B is called a twin pair. If C , D are two (n − d) -dominoes which form a twin pair such that A ∪ B = C ∪ D and { C , D } ≠ { A , B } , then the pair C , D is called a flip of A , B. A family D of (n − d) -dominoes is a tiling of the box [ 0 , 2 ] n if interiors of every two members of D are disjoint and ⋃ B ∈ D B = [ 0 , 2 ] n. An (n − d) -domino tiling D ′ is obtained from an (n − d) -domino tiling D by a flip, if there is a twin pair A , B ∈ D such that D ′ = (D ∖ { A , B }) ∪ { C , D } , where C , D is a flip of A , B. A family of (n − d) -domino tilings of the box [ 0 , 2 ] n is flip-connected, if for every two members D , E of this family the tiling E can be obtained from D by a sequence of flips. In the paper a flip-connected class of (n − d) -domino tilings of the box [ 0 , 2 ] n is described. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
34. Esophageal Motility Disorders: Current Approach to Diagnostics and Therapeutics.
- Author
-
Patel, Dhyanesh A., Yadlapati, Rena, and Vaezi, Michael F.
- Abstract
Dysphagia is a common symptom with significant impact on quality of life. Our diagnostic armamentarium was primarily limited to endoscopy and barium esophagram until the advent of manometric techniques in the 1970s, which provided the first reliable tool for assessment of esophageal motor function. Since that time, significant advances have been made over the last 3 decades in our understanding of various esophageal motility disorders due to improvement in diagnostics with high-resolution esophageal manometry. High-resolution esophageal manometry has improved the sensitivity for detecting achalasia and has also enhanced our understanding of spastic and hypomotility disorders of the esophageal body. In this review, we discuss the current approach to diagnosis and therapeutics of various esophageal motility disorders. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
35. Pathophysiology of Dysphagia in Eosinophilic Esophagitis: Causes, Consequences, and Management.
- Author
-
Young, Edward and Philpott, Hamish
- Subjects
- *
EOSINOPHILIC esophagitis , *DEGLUTITION disorders , *PATHOLOGICAL physiology , *BOLUS (Digestion) - Abstract
Eosinophilic esophagitis (EoE) is a leading cause of food bolus impaction in children and adults. The mechanism of dysphagia in EoE, particularly non-obstructive dysphagia, remains incompletely understood. While fibrostenotic processes appear to be critical in the development of dysphagia, somatosensory dysfunction and dysmotility also contribute. This review considers potential mechanisms of dysphagia and evaluates the utility of current and future treatment strategies in this context. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
36. Teaching EndoFLIP Impedance Planimetry to Practicing Endoscopists: An "Into the Fire" Approach to Simulation.
- Author
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Wong, Harry J., Su, Bailey, Attaar, Mikhail, Kuchta, Kristine, Linn, John G., Haggerty, Stephen P., Denham, Woody, and Ujiki, Michael B.
- Abstract
Background. There are growing interests from practicing endoscopists to implement the functional lumen imaging probe (FLIP) impedance planimetry system. We present a simulation-based curriculum using an "into the fire" approach with hands-on pre- and post-tests to teach the use of this technology. Methods. The curriculum consists of a series of pre-tests, didactic content, mentored hands-on instructions, and post-tests. Pre- and post-testing included a knowledge-based written test, a confidence survey, and an assessment form specific to the hands-on performance of FLIP. Result. Twenty-two practicing physicians completed the curriculum. After course completion, participants had improved knowledge-based written test scores from 6.8±1.7 to 8.9±0.9 (P <0.001), confidence scores from 10.0±5.9 to 22.1±2.6 (P <0.001), and hands-on performance score from 11.4±3.4 to 23.1±2.0 (P <0.001) with significant improvement in all components of the hands-on skills. Conclusion. Our simulation curriculum is effective in improving confidence, knowledge, and technical proficiency when teaching the use of FLIP to practicing physicians. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
37. Molecular Mechanisms of Apoptosis in Naive and Memory Human T Cell Subsets : Effect of Age
- Author
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Gupta, Sudhir, Gupta, Ankmalika, Fulop, Tamas, editor, Franceschi, Claudio, editor, Hirokawa, Katsuiku, editor, and Pawelec, Graham, editor
- Published
- 2019
- Full Text
- View/download PDF
38. Minimal Models of Semi-log-canonical Pairs
- Author
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Ambro, Florin, Kollár, János, Patrizio, Giorgio, Editor-in-Chief, Canuto, Claudio, Series Editor, Coletti, Giulianella, Series Editor, Gentili, Graziano, Series Editor, Malchiodi, Andrea, Series Editor, Marcellini, Paolo, Series Editor, Mezzetti, Emilia, Series Editor, Moscariello, Gioconda, Series Editor, Ruggeri, Tommaso, Series Editor, Codogni, Giulio, editor, Dervan, Ruadhaí, editor, and Viviani, Filippo, editor
- Published
- 2019
- Full Text
- View/download PDF
39. Solid Swallow Examination During High Resolution Manometry and EGJ-Distensibility Help Identify Esophageal Outflow Obstruction in Non-obstructive Dysphagia.
- Author
-
Murray, Fritz Ruprecht, Fischbach, Lara Maria, Schindler, Valeria, Schnurre, Larissa, Hente, Juliane Marie, Tatu, Aurora, and Pohl, Daniel
- Abstract
Single water swallow (SWS) high-resolution manometry (HRM) may miss relevant esophageal motility disorders. Solid test meal (STM) during HRM and lately the functional lumen imaging probe (FLIP) have been shown to be of diagnostic value in the assessment of motility disorders. We aimed to assess the diagnostic yield of STM and FLIP in non-obstructive dysphagia (NOD). Patients assessed for dysphagia with both HRM and FLIP between April 2016 and August 2019 were analyzed for signs of non-obstructive EGJ outflow obstruction (EGJOO) according to Chicago Classification 3.0 (CCv3) and CC adapted for the use with solid swallows (CC-S), followed by an individual group-specific analysis. Five subjects without dysphagia served as control group. Standard HRM- and FLIP-values as well as esophagograms and Eckardt Scores were analyzed. Forty-two patients were identified (male/female, 14/36, median age 62). Twenty-five (59.5%) were diagnosed with EGJOO during STM only (= SWS-negative patients; CC-S). The EGJ distensibility index (EGJ-DI) of symptomatic patients was significantly lower compared to the control group (p = 0.006). EGJ-DI was < 3mm
2 /mmHg in 67% and 88% of patients diagnosed according to CC-S and CCv3, respectively. The IRP during STM showed a significant association to the corresponding EGJ-DI values (p < 0.001). Seventy-six percent of patients received treatment because of additional STM evaluation with a favorable clinical response rate of 89%. STM and FLIP identify EGJOO in symptomatic patients with normal SWS during HRM. STM resembles an inexpensive and clinically meaningful option to diagnose motility disorders and helps to select patients for interventional treatment. [ABSTRACT FROM AUTHOR]- Published
- 2022
- Full Text
- View/download PDF
40. Some remarks on finiteness of extremal rays of divisorial type.
- Author
-
Yoshio FUJIMOTO
- Subjects
- *
FINITE, The , *ENDOMORPHISMS - Abstract
Let X be a normal Q-factorial projective variety with at most log canonical singularities. We shall give a sufficient condition for the existence of at most finitely many KX-negative extremal rays R(C NE(X) of divisorial type. As an application, we show that for a nonisomorphic surjective endomorphism f:X - X of a normal projective Q-factorial terminal 3-fold X with (X) > 0, a suitable power fk (k > 0) of f descends to a nonisomorphic surjective endomorphism g:Xmin - Xmin of a minimal model Xmin of X. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
41. Real-time intraoperative functioning lumen imaging probe during endoscopic per-oral pyloromyotomy (pop).
- Author
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Fathalizadeh, Alisan, Klingler, Michael, Landreneau, Joshua, Allemang, Matthew, Rodriguez, John, Ponsky, Jeffrey, and El-Hayek, Kevin
- Subjects
- *
GASTRIC emptying , *MEASURING instruments , *PYLORUS , *SURGICAL complications , *GASTROPARESIS - Abstract
Background: Endoscopic per-oral pyloromyotomy (POP) has emerged as a safe and effective first line option in medically refractory gastroparesis. Determining the appropriate extent of the pyloromyotomy continues to present a challenge as there are no standardized tools for measuring changes in pyloric distensibility during the procedure. The objective of this study was to evaluate the utility of using impedance planimetry with endoscopic functional luminal imaging probe (FLIP) to measure changes in pyloric distensibility after POP, and to compare these changes with improvement in symptoms and objective gastric emptying. Methods: Patients with medically refractory gastroparesis underwent POP with FLIP measurements of the pylorus (EndoFLIP®, Medtronic, Fridley MN). FLIP measurements, as well as changes in symptoms measured by the validated gastroparesis cardinal symptom index (GCSI) and scintigraphic gastric emptying studies (GES), were evaluated before and after POP. Results: A total of 14 patients underwent measurement with FLIP during POP, 12 of whom had pre- and post-POP measurements. Mean pyloric diameter increased by 1.4 mm, from 13.9 mm to 15.3 mm (p = 0.0012). Mean distensibility index increased from 6.2 mm2/mmHg to 9.1 mm2/mmHg (p = 0.0074). Successful division of the pylorus was achieved in 100% of patients with a mean operative time of 36 min and no perioperative complications. The mean length of stay was 0.7 days (0–3 days). Post-POP mean GCSI score improved from 2.97 to 2.28 at a mean follow-up time of 27 days (p < 0.001). Objective improvement in gastric emptying was observed in 80% of patients with scintigraphic GES, with mean four-hour retention decreasing from 46.3% to 32.4% (p < 0.007). Conclusions: FLIP is a safe and feasible tool to provide objective measurements during POP. Larger cohorts with longer follow-up are required to determine if measured improvements in pyloric diameter and distensibility are predictive of sustained improvements in GCSI and GES. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
42. Differential Fault Attack on Kreyvium & FLIP.
- Author
-
Roy, Dibyendu, Bathe, Bhagwan, and Maitra, Subhamoy
- Subjects
- *
STREAM ciphers , *FAULT location (Engineering) , *CIPHERS , *PORTABLE computers - Abstract
In this article, we propose key recovery attack on two stream ciphers: Kreyvium and FLIP $_{530}(42,128,360)$ 530 (42 , 128 , 360) using Differential Fault Attack (DFA) technique. These two ciphers are being used in Fully Homomorphic Encryption (FHE) due to their low error growth during keystream generation. Kreyvium is an NFSR-based stream cipher and FLIP is a permutation-based stream cipher. We first show that the complete state of the Kreyvium can be recovered by injecting 3 faults and considering 450 many keystream bits. In case of FLIP, we show that if there is a 1-bit fault in the state of the cipher then from 9000 normal and faulty keystream bits the state (i.e., the secret key) of the cipher can be recovered. For single bit fault, one will require to solve a system of equations for each 530 possible fault locations to recover the correct key of FLIP. To the best of our knowledge, this is the first article which analyzes the security of these two FHE supported stream ciphers under DFA and it has been observed that DFA completely reveals the secret keys of these two ciphers with very minimal faults. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
43. A new perspective of triptolide-associated hepatotoxicity: the relevance of NF-κB and NF-κB-mediated cellular FLICE-inhibitory protein
- Author
-
Ziqiao Yuan, Zihang Yuan, Muhammad Hasnat, Haoran Zhang, Peishi Liang, Lixin Sun, Zhenzhou Jiang, and Luyong Zhang
- Subjects
Triptolide ,LPS ,TNF-α ,NF-κB ,FLIP ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Previously, we proposed a new perspective of triptolide (TP)-associated hepatotoxicity: liver hypersensitivity upon lipopolysaccharide (LPS) stimulation. However, the mechanisms for TP/LPS-induced hepatotoxicity remained elusive. The present study aimed to clarify the role of LPS in TP/LPS-induced hepatotoxicity and the mechanism by which TP induces liver hypersensitivity upon LPS stimulation. TNF-α inhibitor, etanercept, was injected intraperitoneally into mice to investigate whether induction of TNF-α by LPS participated in the liver injury induced by TP/LPS co-treatment. Mice and hepatocytes pretreated with TP were stimulated with recombinant TNF-α to assess the function of TNF-α in TP/LPS co-treatment. Additionally, time-dependent NF-κB activation and NF-κB-mediated pro-survival signals were measured in vivo and in vitro. Finally, overexpression of cellular FLICE-inhibitory protein (FLIP), the most potent NF-κB-mediated pro-survival protein, was measured in vivo and in vitro to assess its function in TP/LPS-induced hepatotoxicity. Etanercept counteracted the toxic reactions induced by TP/LPS. TP-treatment sensitized mice and hepatocytes to TNF-α, revealing the role of TNF-α in TP/LPS-induced hepatotoxicity. Mechanistic studies revealed that TP inhibited NF-κB dependent pro-survival signals, especially FLIP, induced by LPS/TNF-α. Moreover, overexpression of FLIP alleviated TP/LPS-induced hepatotoxicity in vivo and TP/TNF-α-induced apoptosis in vitro. Mice and hepatocytes treated with TP were sensitive to TNF-α, which was released from LPS-stimulated immune cells. These and other results show that the TP-induced inhibition of NF-κB-dependent transcriptional activity and FLIP production are responsible for liver hypersensitivity.
- Published
- 2020
- Full Text
- View/download PDF
44. hnRNPK knockdown alleviates NLRP3 inflammasome priming by repressing FLIP expression in Raw264.7 macrophages
- Author
-
Junxia Feng, Hongyan Li, Jingchun Li, Ping Meng, Lina Wang, Chunli Liu, Shili Zhao, Wei Sun, and Yunfang Zhang
- Subjects
hnrnpk ,nlrp3 inflammasome ,flip ,macrophages ,lps/atp ,il-1β ,il-18 ,chronic kidney disease ,Pathology ,RB1-214 ,Biology (General) ,QH301-705.5 - Abstract
Objectives: Inflammation is an important predisposing and progressive factor in chronic kidney disease (CKD). Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is associated with many fundamental cellular processes, but in chronic inflammatory pathologies remains unclear. Methods: An in vitro peripheral inflammation model was established using lipopolysaccharide (LPS)-stimulated mouse RAW264.7 macrophages, followed by inflammasome activation by ATP treatment. Knockdown of hnRNPK by sihnRNPK and FLICE-like inhibitory protein (FLIP) by siFLIP transfection were achieved in Raw264.7 macrophages. ELISA was used to determine the expression of IL-1β, IL-18 and TNF-α. Real time PCR was applied to detect the mRNA levels of hnRNPK, NOD-like receptors family pyrin domain-containing 3 (NLRP3), FLIP, Caspase-1, IL-1β and IL-18. Western blot and immunofluorescence were performed to detect relevant protein expressions. Co-immunoprecipitation (Co-IP) was used to assess the interaction of hnRNPK with FLIP. Results: Results showed that LPS plus ATP activated NLRP3 inflammasome, which evidenced by the up-regulation of TNF-α, IL-1β and IL-18. Notably, hnRNPK and FLIP were significantly up-regulated in activated NLRP3 inflammasome of macrophages. HnRNPK or FLIP knockdown significantly suppressed the activation of NLRP3 inflammasome, as reflected by down-regulation of Caspase-1, IL-1β and IL-18. Importantly, hnRNPK could directly bind to FLIP in activated NLRP3 inflammasome. Discussion: Our findings suggest that hnRNPK could promote the activation of NLRP3 inflammasome by directly binding FLIP, which might provide potential new therapeutic targets for CKD.
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- 2020
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45. Exploring New COVID-19 Incertitude: JN.1 Variant- JN.1: The Queer Bird Among Omicron Sublineages.
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Ray SK and Mukherjee S
- Abstract
COVID-19 pandemic is casting a long shadow, and the appearance of the JN.1 variety calls attention to the necessity of maintaining heightened awareness. It considers the strength that has been developed via immunization programs and the necessity of global collaboration to find a solution in light of the emergence of new strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Phylogenetically, the SARS-CoV-2 Omicron XBB lineages, which include EG.5.1 and HK.3, are different from the SARS-CoV-2 BA.2.86 lineage, which was initially discovered in August 2023. More than 30 mutations in the spike (S) protein are carried by BA.2.86 compared to XBB and BA.2, suggesting a high potential for immune evasion. JN.1 (BA.2.86.1.1), a descendant of BA.2.86, appeared in late 2023 after the format had undergone evolution. JN.1 carries three mutations in proteins that do not include S, as well as S:L455S. As previously demonstrated, the HK.3 and other "FLip" variations possess the S:L455F mutation, which enhances transmissibility and immune escape capacity in comparison to the parental EG.5.1 variety. This mutation is a characteristic of JN.1. The COVID-19 virus is dynamic and evolves over time. New varieties can sometimes spread more quickly or effectively after these alterations. If that happens, the new variant has a chance to outpace the current varieties in terms of frequency., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
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- 2024
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46. Highest Order Voronoi Processing on Apache Spark
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Pradnyana, Putu Eka Budi, Adhinugraha, Kiki Maulana, Alamri, Sultan, Hutchison, David, Series Editor, Kanade, Takeo, Series Editor, Kittler, Josef, Series Editor, Kleinberg, Jon M., Series Editor, Mattern, Friedemann, Series Editor, Mitchell, John C., Series Editor, Naor, Moni, Series Editor, Pandu Rangan, C., Series Editor, Steffen, Bernhard, Series Editor, Terzopoulos, Demetri, Series Editor, Tygar, Doug, Series Editor, Weikum, Gerhard, Series Editor, Gervasi, Osvaldo, editor, Murgante, Beniamino, editor, Misra, Sanjay, editor, Stankova, Elena, editor, Torre, Carmelo M., editor, Rocha, Ana Maria A.C., editor, Taniar, David, editor, Apduhan, Bernady O., editor, Tarantino, Eufemia, editor, and Ryu, Yeonseung, editor
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- 2018
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47. Tools in Analyzing Linear Approximation for Boolean Functions Related to FLIP
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Maitra, Subhamoy, Mandal, Bimal, Martinsen, Thor, Roy, Dibyendu, Stănică, Pantelimon, Hutchison, David, Series Editor, Kanade, Takeo, Series Editor, Kittler, Josef, Series Editor, Kleinberg, Jon M., Series Editor, Mattern, Friedemann, Series Editor, Mitchell, John C., Series Editor, Naor, Moni, Series Editor, Pandu Rangan, C., Series Editor, Steffen, Bernhard, Series Editor, Terzopoulos, Demetri, Series Editor, Tygar, Doug, Series Editor, Weikum, Gerhard, Series Editor, Chakraborty, Debrup, editor, and Iwata, Tetsu, editor
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- 2018
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48. Design and Motion Planning of a Metamorphic Flipping Robot
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Yuntao Guan, Zheming Zhuang, Chunsong Zhang, Zhao Tang, Ze Zhang, and Jian S. Dai
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reconfigure ,legged robot ,flexible waist ,flip ,Materials of engineering and construction. Mechanics of materials ,TA401-492 ,Production of electric energy or power. Powerplants. Central stations ,TK1001-1841 - Abstract
With the advantages of high flexibility, strong adaptability, etc., the legged robot can help humans to complete numerous complicated tasks. In this paper, a kind of reconfigurable legged robot with a flexible waist was proposed. Compared with the common robots with a rigid trunk, the proposed robot can twist its waist flexibly. Through analysis, it is found that the flexible waist can improve the trunk workspace, foot endpoints’ workspace and static stability margin of the robot, and further enhance the motion performance of the robot. Meanwhile, by imitating the creatures in nature, the motion gait planning of the robot was provided. Additionally, the proposed robot has excellent reconfigurable characteristics, and can flexibly transform among three forms to adapt to different working environments and accomplish different tasks. Further, after capsizing, the robot can complete the motion of turning over more easily. In this paper, the reconfiguration posture and the motion of turning over of the robot were planned in detail, and finally verified by ADAMS simulation.
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- 2022
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49. Intraoperative FLIP distensibility during POEM varies according to achalasia subtype.
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Holmstrom, Amy L., Campagna, Ryan A. J., Alhalel, Jonathan, Carlson, Dustin A., Pandolfino, John E., Hungness, Eric S., and Teitelbaum, Ezra N.
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ESOPHAGEAL achalasia , *ESOPHAGOGASTRIC junction , *TREATMENT effectiveness , *KRUSKAL-Wallis Test , *CHI-squared test , *ESOPHAGEAL surgery , *ESOPHAGOSCOPY , *ESOPHAGUS , *DIAGNOSTIC imaging , *ENDOSCOPY ,DIGESTIVE organ surgery - Abstract
Background: The functional luminal imaging probe (FLIP) can be used to measure the esophagogastric junction distensibility index (DI) during myotomy for achalasia and increased DI has been shown to predict superior clinical outcomes. The objective of this study was to determine if the intraoperative DI and the changes produced by per oral endoscopic myotomy (POEM) differed between achalasia subtypes.Methods: FLIP measurements were performed during POEM for achalasia at a single institution. DI (defined as the minimum cross-sectional area (CSA) at the EGJ divided by distensive pressure) was measured at three time points: after induction of anesthesia, after submucosal tunneling, and after myotomy. Measurements were reported at the 40 mL fill volume for the 8 cm FLIP (EF-325) and at the 60 mL fill volume for the 16 cm FLIP (EF-322). Measurements were compared using chi-square and Kruskal-Wallis tests.Results: 142 patients had intraoperative FLIP performed during POEM for achalasia between 2012 and 2019 (30 type I, 68 type II, 27 type III, and 17 variant). Patients with type I achalasia had a significantly higher induction DI (median 1.7 mm2/mmHg) than type II (0.8 mm2/mmHg), type III (0.9 mm2/mmHg), and variants (1.1 mm2/mmHg; p < 0.001). These differences persisted after submucosal tunneling and final DI after myotomy was also significantly higher in type I patients (median 8.0 mm2/mmHg) compared to type II (5.8 mm2/mmHg), type III (3.9 mm2/mmHg), and variants (5.4 mm2/mmHg; p < 0.001). Achalasia subtypes were found to have similar CSA at all time points, whereas pressure differed with type I having the lowest pressure and type III the highest.Conclusion: The DI at each operative step during POEM was found to differ significantly between achalasia subtypes. These differences in DI were due to pressure, as CSA was similar between subtypes. Achalasia subtype should be accounted for when using FLIP as an intraoperative calibration tool and in future studies examining the relationship between DI and clinical outcomes. [ABSTRACT FROM AUTHOR]- Published
- 2021
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50. Intraoperative use of FLIP is associated with clinical success following POEM for achalasia.
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Holmstrom, Amy L., Campagna, Ryan A. J., Cirera, Arturo, Carlson, Dustin A., Pandolfino, John E., Teitelbaum, Ezra N., and Hungness, Eric S.
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- *
ESOPHAGEAL achalasia , *ESOPHAGOGASTRIC junction , *MANN Whitney U Test , *TREATMENT effectiveness , *VIDEO recording , *SURGICAL robots - Abstract
Background: Esophagogastric junction distensibility index (DI), measured using the functional luminal imaging probe (FLIP), correlates with symptomatic outcomes after interventions for achalasia. The objective of this study was to determine if the intraoperative measurement of DI using FLIP was associated with improved clinical outcomes following per-oral endoscopic myotomy (POEM) for achalasia when compared with procedures in which FLIP was not utilized. Methods: Patients undergoing POEM from 2012 to 2017 at a single institution by a single surgeon were studied. Use of FLIP during this time period was based on catheter and technician availability, resulting in two patient cohorts. In patients in whom FLIP was used, operative video recordings were reviewed to determine when DI measurements led to the performance of additional myotomy. Postoperative Eckardt symptom scores (ES) at 12 months and postoperative physiologic studies were compared between patients with and without intraoperative FLIP. Associations were assessed using Mann–Whitney U and Chi-square tests. Results: 143 patients were included in the analysis (61 with intraoperative FLIP and 82 without FLIP). Video recordings were available for 85% of the FLIP cohort. Review of these operative recordings revealed that 65% of patients who underwent FLIP had additional myotomy performed following the initial postmyotomy FLIP measurement. At 12 months after POEM, the FLIP cohort had significantly more clinical successes (defined as ES ≤ 3) than patients in whom FLIP was not used (93% vs. 81%, p < 0.05). Conclusions: Use of intraoperative FLIP during POEM resulted in the surgeon performing additional myotomy in over half of cases and was associated with improved clinical outcomes. This study demonstrates the potential for a FLIP-tailored myotomy to improve outcomes in patients undergoing surgical myotomy for achalasia. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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