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Differential Splicing of Skipped Exons Predicts Drug Response in Cancer Cell Lines

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Genomics, Proteomics & Bioinformatics 2021年第6期19卷 901-912页

作者： Edward simpson Steven Chen jill L.Reiter Yunlong Liu Center for Computational Biology and Bioinformatics Indiana University School of MedicineIndianapolisIN 46202USA Department of BioHealth Informatics School of Informatics and ComputingIndiana University-Purdue University IndianapolisIndianapolisIN 46202USA Department of Medical and Molecular Genetics Indiana University School of MedicineIndianapolisIN 46202USA

Alternative splicing of pre-mRNA transcripts is an important regulatory mechanism that increases the diversity of gene products in *** studies have linked specific transcript isoforms to altered drug response in cancer;however,few algorithms have incorporated splicing information into drug response *** this study,we evaluated whether basal-level splicing information could be used to predict drug sensitivity by constructing doxorubicin-sensitivity classification models with splicing and expression *** detailed splicing differences between sensitive and resistant cell lines by implementing quasi-binomial generalized linear modeling(QBGLM)and found altered inclusion of 277 skipped *** additionally conducted RNA-binding protein(RBP)binding motif enrichment and differential ex-pression analysis to characterize cis-and trans-acting elements that potentially influence doxorubicin response-mediating splicing *** results showed that a classification model built with skipped exon data exhibited strong predictive *** discovered an association between differentially spliced events and epithelial-mesenchymal transition(EMT)and observed motif enrichment,as well as differential expression of RBFOX and ELAVL RBP family *** work demonstrates the potential of incorporating splicing data into drug response algorithms and the utility of a QBGLM approach for fast,scalable identification of relevant splicing differences between large groups of samples.

关键词： Alternative splicing Transcript isoform Splicing regulation Drug sensitivity Precision medicine

Persistent diarrhea with petechial rash-unusual pattern of light chain amyloidosis deposition on skin and gastrointestinal biopsies:A case report

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World journal of Clinical Cases 2022年第28期10卷 10252-10259页

作者： Shawna E Bilton Nikhil Shah Diana Dougherty Sarah simpson Alex Holliday Farhad Sahebjam Douglas j Grider Department of Basic Science Education Virginia Tech Carilion School of MedicineRoanokeVA 24016United States Department of Internal Medicine Carilion ClinicRoanokeVA 24016United States Gastroenterology and Hepatology Section Department of Internal MedicineCarilion ClinicRoanokeVA 24016United States Dermatology Section Department of Internal MedicineCarilion ClinicRoanokeVA 24016United States Dominion Pathology Associates RoanokeVA 24018United States

BACKGROUND Amyloidosis is a rare disease characterized by extracellular deposition of misfolded protein aggregated into insoluble *** involvement in systemic amyloidosis is common,but is often subclinical or presents as vague and nonspecific *** is rare for gastrointestinal symptoms to be the main presenting symptom in patients with systemic amyloidosis,causing it to be undiagnosed until late-stage *** SUMMARY A 53 year-old man with diarrhea,hematochezia,and weight loss presented to a community *** with biopsy at that time was suspicious for Crohn *** to worsening symptoms including nausea,vomiting,and a new petechial rash,an abdominal fat pad biopsy was *** biopsy showed papillary and adnexal dermal amyloid deposition,in a pattern usually seen with cutaneous ***,Cytokeratin 5/6 was negative,excluding cutaneous *** patterns of nodular amyloidosis,subcutaneous amyloid deposits and perivascular amyloid were not *** Acid-Schiff stain was negative for lipoid proteinosis,Congo red was positive for apple green birefringence on polarization and amyloid typing confirmed amyloid light chain *** endoscopic biopsies of the gastrointestinal tract showed amyloid deposition from the esophagus to the rectum,in a pattern usually seen in serum amyloid A in the setting of chronic inflammatory diseases,including severe inflammatory bowel *** marrow biopsy showed kappa-restricted plasma cell *** Described is an unusual presentation of primary systemic amyloidosis,highlighting the risk of misdiagnosis with subsequent significant organ dysfunction and high mortality.

关键词： Light chain amyloidosis Diarrhea Endoscopy Petechial rash Plasma cell dyscrasia Case report

Expression levels of aminopeptidase-N genes in the lightbrown apple moth, Epiphyas postvittana

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Insect Science 2008年第6期15卷 505-512页

作者： Robert M. simpson joanne Poulton Ngaire P. Markwick Horticulture and Food Research Institute Palmerston North Horticulture and Food Research Institute Auckland New Zealand

Five aminopeptidase-N genes （EpAPN1-5） of the tortricid moth Epiphyas postvittana have been isolated from a midgut expressed sequence tag （EST） library. Relative RNA expression of these genes was measured by quantitative reverse transcription polymerase chain reaction using actin as a reference gene. Measurements were made on various tissues of fifth instar larvae, over all stages of the life cycle and under differing dietary conditions： different protein sources and levels, and in presence of trypsin and metalloprotease inhibitors. Gene expression for all five genes was the greatest in midgut tissue, but was also detected in the hindgut, fat body and Malpighian tubules. EpAPN4 was consistently the highest expressed, with EpAPN3 at about half that level; EpAPN5 was the least expressed. During larval stages expression was high, generally increasing over the instars, after an early peak as neonates or first instars. Expression in other life stages was much lower. Males and females showed differing expression in the pupal and adult stages： female expression was higher in the pupa, this reversed in the adult. Gene expression levels and ratios both changed with diet. A natural apple leaf diet depressed levels. Diets with the most impaired amino acid balance induced the greatest change; generally EpAPN1 increased by the greatest proportion. The addition of proteinase inhibitor also increased gene expression, and it was noteworthy that the trypsin inhibitor addition, which has been shown to double aminopeptidase activity, also doubled levels of gene expression.

关键词： aminopeptidase Epiphyas postvittana Q-PCR

Effect of Heat Treatment on Corrosion Performance of Duplex Steel COR 25

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journal of Materials Science & Technology 1989年第3期5卷 199-202页

作者：李冬贵 j.P.simpson R.Schenk Dalian Acid Proof Pump Plant China Sulzer Bros.Ltd WinterthurSwitzerland

The effect of heat treatment on the corrosion performance of austenitic-ferritic duplex stain- less steel COR 25 in aqueous solution containing 60%H_3PO_4+4%H_2SO_4+1500 ppm Cl^- at 95℃ was in- *** the solution temperature was increased from 950℃ to 1230℃,the corrosion resistance increased by two orders of magnitude, as shown by electrochemical measurements,im- mersion tests and direct observation under the scanning electron *** specimens heat treated at solution temperatures of 950℃ and 1030℃ were severely corroded along the phase boundaries;specimens treated at 113C℃ and 1230℃ tended to selective corrosion caused by the dissimilar chromium contents of the aus- tenite and ferrite phases after heat treatment.

关键词： heat treatment duplex stainless steel electrochemical behavior corrosion

Effect of Temperature and Chloride Ion Concentration on the Electrochemical Behaviour of Stainless Steel

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journal of Materials Science & Technology 1989年第3期5卷 203-206页

作者：李冬贵 j.P.simpson R.Schenk Dalian Acid Proof Pump Plant China Sulzer Bros.Ltd WinterthurSwitzerland

The effect of temperature and chloride ion concentration on the electrochemical behaviour of austenitic-ferritic duplex stainless steel COR 25 in an aqueous solution of 60%H_3PO_4+4%H_2SO_4 is studied in this paper. The experiments show that the anodic active peak current on potentiodynamic polarization increases by an order of magnitude with an in- crease of temperature from 50℃ and with an increase of chloride ion from<1 mg/1 to 1500mg/1. Compared with the other materials tested, the austenitic-ferritic duplex stainless steel shows favourable corrosion characteristics in electrochemical tests,being comparable to the fully austenitic alloy Sanicro 28,which has a higher chromium and nickel content,and is much better than *** of the duplex material is normally phase selec- tive,with phase boundary attack after unfavour- able heat treatments.

关键词： temperature chloride corrosion behaviour duplex stainless steel

The overview of antimicrobial peptide-coated implants against oral bacterial infections

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Aggregate

Aggregate 2023年第3期4卷 3-18页

作者： Zhe Sun Li Ma Xiaodong Sun Alastair j.Sloan Neil M.O’Brien-simpson Wenyi Li Department of Stomatology Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinanShandongChina Department of Endodontics Gaoxin branch of Jinan Stomatological HospitalJinanShandongChina Melbourne Dental School Division of Basic and Clinical Oral SciencesThe University of MelbourneCarltonVictoriaAustralia ACTV Research Group Melbourne Dental SchoolDivision of Basic and Clinical Oral SciencesThe Bio21 Institute of Molecular Science and BiotechnologyThe University of MelbourneCarltonVictoriaAustralia

Dental implants are the most common therapeutic approach for resolving tooth loss and *** technical advances in treatment,implant failure rates can be as high as 23%with the major cause of peri-implantitis:a multi-species bacterial *** an annual growth rate in implant placements of 8.78%per annum,implant failure caused by bacterial infection is a significant oral and general health *** rise in antibiotic resistance in oral bacteria further adds pressure to implant failure;thus,there is a need for adjunctive therapy to improve implant *** to the broad spectrum of activity and a low risk of inducing bacterial resistance,peptide antibiotics are emerging as a promising implant coating material to reduce/prevent peri-implantitis and improve dental implant success *** this review,we summarised the current strategies of coating antimicrobial peptides(AMPs)onto dental implant material surfaces with multi-functional properties to enhance osteoblast growth and prevent bacterial *** review compared the recent reported literature on dental implant coating with AMPs,which will provide an overview of the current dental implant coating strategies using AMPs and insights for future clinical applications.

关键词： antimicrobial coating antimicrobial peptides dental implants implant-associated infection peptide release peri-implant disease

Laser ablation(in situ)Lu-Hf dating of magmatic fluorite and hydrothermal fluorite-bearing veins

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Geoscience Frontiers 2023年第6期14卷 142-154页

作者： Stijn Glorie jacob Mulder Martin Hand Adrian Fabris Alexander simpson Sarah Gilbert Department of Earth Sciences University of AdelaideSA 5005Australia Geological Survey of South Australia Department for Energy and MiningAdelaideSA 5005Australia Adelaide Microscopy University of AdelaideSA 5005Australia

Fluorite(CaF_(2))is a common hydrothermal mineral,which precipitates from fluorine-rich fluids with an exceptional capacity to transport metals and Rare Earth Elements(REEs).Hence,the ability to date fluorite has important implications for understanding the timing of metal transport in hydrothermal *** we present,for the first time,fluorite Lu-Hf dates from fluorite-carbonate veins from the Olympic Cu-Au Province in South *** fluorite dates were obtained in situ using the recently developed LA-ICP-MS/MS Lu-Hf dating method.A fluorite-calcite age of 1588±19 Ma was obtained for the Torrens Dam prospect,consistent with the timing of the formation of the nearby Olympic Dam iron-oxide copper gold Breccia *** in the overlying Neoproterozoic successions were dated at 502±14 Ma,indicating a temporal link between Cu-sulphide remobilisation and the Delamerian ***,we present a multi-session reproducible date for magmatic fluorite from a monzogranite in the Pilbara Craton(Lu-Hf age of 2866±19 Ma).This age is consistent with a garnet Lu-Hf age from the same sample(2850±12 Ma)and holds potential to be developed into a secondary reference material for future fluorite Lu-Hf dating.

关键词： Reaction-cell ICP-MS In-situ geochronology Fluorite-calcite veins Iron oxide copper-gold Critical mineral exploration Rare Earth Elements

In situ Lu–Hf phosphate geochronology:Progress towards a new tool for space exploration

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Geoscience Frontiers 2022年第3期13卷 164-167页

作者： Stijn Glorie Thomas Burke Martin Hand Alexander simpson Sarah Gilbert Benjamin Wade Department of Earth Sciences The University of AdelaideSA 5005 AdelaideAustralia Adelade Microscopy The University of AdelaideSA 5005 AdelaideAustralia

Geochronology is fundamental to understanding planetary ***,as space exploration continues to expand,traditional dating methods,involving complex laboratory processes,are generally not realistic for unmanned space ***-style planetary exploration missions require dating methods that can(1)rapidly resolve age information on small samples,(2)be applied to minerals common in mafic rocks,and(3)be based on technologies that could be installed on future rover *** demonstrate the application of rapid in situ microanalytical Lu–Hf phosphate geochronology using samples of pallasite meteorites,which are representative examples of the deep interiors of differentiated planetoids that are generally difficult to *** pallasites were dated by laser ablation tandem mass-spectrometry(LA-ICP-MS/MS),demonstrating a rapid novel method for exploring planetary *** formation ages for individual pallasites agree with traditional methods and have<2%uncertainty,opening an avenue of opportunity for remote micro-analytical space exploration.

关键词： Pallasite meteorites Lu-Hf geochronology Laser ablation tandem mass-spectrometry Micro-analytical planetary exploration

Lowering the cost of large-scale energy storage:High temperature adiabatic compressed air energy storage

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Propulsion and Power Research 2017年第2期6卷 126-133页

作者： B.Cárdenas A.j.Pimm B.Kantharaj M.C.simpson j.A.Garvey S.D.Garvey Department of Mechanical.Materials and Manufacturing Engineering Faculty of Engineering.University of Nottingham.Nottingham NG72RD United Kingdom Centre for Integrated Energy Research School of Chemical and Process Engineering.University of Leeds.Leeds LS29DTUnited Kingdom School of Mechanical Engineering University of LeedsLeeds LS29DTUnited Kingdom

Compressed air energy storage is an energy storage technology with strong potential to play a significant role in balancing energy on transmission networks,owing to its use of mature technologies and low cost per unit of storage *** compressed air energy storage(A-CAES)systems typically compress air from ambient temperature in the charge phase and expand the air back to ambient temperature in the discharge *** papers explores the use of an innovative operating scheme for an A-CAES system aimed at lowering the total cost of the system for a given exergy storage *** configuration proposed considers preheating of the air before compression which increases the fraction of the total exergy that is stored in the fom of high-grade heat in comparison to existing designs in which the main exergy storage medium is the compressed air *** a high fraction of the total exergy as heat allows reducing the capacity of costly pressure stores in the system and replacing it with cheaper thermal energy ***,a configuration that integrates a system based on the aforementioned concept with solar thermal power or low-medium grade waste heat is introduced and thoroughly discussed.

关键词： High temperature compressed air energy storage(CAES) Preheating of air Generation integrated energy storage Electric grid balancing Electricity storage Renewable generation intermittence