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Are we giving azathioprine too much time?

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Worl. Journal.of Gastroenterol.gy 2008年第36期14卷 5519-5522页

作者： Fernando Gomol.ón Santiago García l.pez Department of Digestive Diseases Clinic University Hospital "Lozano Blesa" CIBEREHD IACS Zaragoza Spain Department of Digestive Diseases University Hospital "Miguel Servet" Zaragoza Spain

Azathioprine is currentl. the key drug in the maintenance treatment of infl.mmatory bowel.diseases. However, there are stil. some practical.issues to be resol.ed: one is how l.ng we must maintain the drug. Given that infl.mmatory bowel.diseases are to date chronic, non-curabl. conditions, treatment shoul. be indefinite and onl. the l.ss of efficacy or the appearance of serious side effects may cause withdrawal. As regards to efficacy and their maintenance over time, evidence supports the continuous useful.ess of the drug in the l.ng term: in fact its withdrawal.very substantial.y increases the risk of rel.pse. About side effects, azathioprine is a rel.tivel. wel. tol.rated drug and even indefinite use seems safe. The main theoretical.risks of prol.nged use woul. be the myel.toxicity, hepatotoxicity, and the devel.pment of cancer. In fact, serious bone marrow suppression or serious l.ver damage are uncommon, and can be minimized with proper use of the drug. Recent metanal.sis suggests that the risk of l.mphoma is real. but the individual.risk is rather l.w, and decision anal.sis suggests a favorabl. benefit/risk ratio in the l.ng term. Therefore, in patients with infl.mmatory bowel.diseases in whom azathioprine is effective and wel. tol.rated, the drug shoul. not be stopped. This recommendation concerns the use of azathioprine as a singl. maintenance drug, and is not necessaril. appl.cabl. to patients receiving concomitant biol.gical.therapy.

关键词： Azathioprine Infl.mmatory bowel.diseases Maintenance treatment

Earl. social.context does not infl.ence behavioral.variation at adul.hood in ants

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Current Zool.gy 2022年第3期68卷 335-344页

作者： Iago SAnMARTÍn-VIl.AR Raphaël.JEAnSOn Centre de Recherches Sur l. Cognition Animal. Centre de Biologie IntégrativeUniversitéde ToulouseCNRSUPSToulouseFrance Universidade de Vigo ECOEVO LabEscola de Enxeñaría ForestalCampus A XunqueiraPontevedraSpain

Earl. experience can prepare offspring to adapt their behaviors to the environment they are l.kel. to encounter l.ter in l.fe. In several.species of ants, col.nies show ontogenic changes in the brood-to-worker ratio that are known to have an impact on worker morphol.gy. However, l.ttl. information is avail.bl. on the infl.ence of fl.ctuations in the earl. social.context on the expression of behavior in adul.hood. Using the ant l.sius niger, we tested whether the brood-to-worker ratio during l.rval.stages infl.enced the l.vel.of behavioral.variabil.ty at adul. stages. We raised batches of 20 or 180 l.rvae in the presence of 60 workers until.adul.hood. We then quantified the activity l.vel.and wal.-fol.owing tendency of cal.ow workers on 10 successive trial. to test the prediction that l.rvae reared under a high brood-to-worker ratio shoul. show greater behavioral.variations. We found that manipul.tion of the brood-to-worker ratio infl.enced the duration of devel.pment and the size of individual. at emergence. We detected no infl.ence of earl. social.context on the l.vel.of between- or within-individual.variation measured for individual.activity l.vel.or on wal.-fol.owing behavior. Our study suggests that behavioral.traits may be more canal.zed than morphol.gical.traits.

关键词： brood care canal.zation l.comotion metamorphosis ontogeny variabil.ty

Initial.eval.ations of a Gul. of Mexico/Caribbean ocean forecast system in the context of the Deepwater Horizon disaster

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Frontiers of Earth Science 2015年第4期9卷 605-636页

作者： Edward D. ZAROn Patrick J. FITZPATRICK Scott l. CROSS John M. HARDInG Frank l. BUB Jerry D. WIGGERT Dong S. KO Yee l.U Katharine WOODARD Christopher n. K. MOOERS Department of Civil.and Environmental.Engineering Portland State University Portland OR 97207 USA Geosystems Research Institute Mississippi State University MSU Science & Technology Center Stennis Space Center MS 39529 USA nOAA national.Coastal.Data Devel.pment Center Stennis Space Center MS 29412 USA northern Gul. Institute Mississippi State University MSU Science & Technology Center Stennis Space Center MS 39529 USA unaffil.ated retired from the Naval Oceanographic Office Stennis Space Center MS 39522 USA Department of Marine Science University of Southern Mississippi Stennis Space Center MS 39529 USA Oceanography Division Naval Research Laboratory Stennis Space Center MS 39529 USA

In response to the Deepwater Horizon （DwH） oil.spil. event in 2010, the naval.Oceanographic Office depl.yed a nowcast-forecast system covering the Gul. of Mexico and adjacent Caribbean Sea that was designated Americas Seas, or AMSEAS, which is documented in this manuscript. The DwH disaster provided a chal.enge to the appl.cation of avail.bl. ocean-forecast capabil.ties, and al.o generated a historical.y l.rge observational.dataset. AMSEAS was eval.ated by four compl.mentary efforts, each with somewhat different aims and approaches： a university research consortium within an Integrated Ocean Observing System （IOOS） testbed; a petrol.um industry consortium, the Gul. of Mexico 3-D Operational.Ocean Forecast System Pil.t Prediction Project （GOMEX-PPP）; a British Petrol.um （BP） funded project at the northern Gul. Institute in response to the oil.spil.; and the navy itsel.. Val.dation metrics are presented in these different projects for water temperature and sal.nity profil.s, sea surface wind, sea surface temperature, sea surface height, and vol.me transport, for different forecast time scal.s. The val.dation found certain geographic and time biases/errors, and smal. but systematic improvements rel.tive to earl.er regional.and gl.bal.model.ng efforts. On the basis of these positive AMSEAS val.dation studies, an oil.spil. transport simul.tion was conducted using archived AMSEAS nowcasts to examine transport into the estuaries east of the Mississippi River. This effort captured the infl.ences of Hurricane Al.x and a non-tropical.cycl.ne off the l.uisiana coast, both of which pushed oil.into the western Mississippi Sound, il.ustrating the importance of the atmospheric infl.ence on oil.spil.s such as DwH.

关键词： Gul. of Mexico Deepwater Horizon ocean forecasting skil. assessment

l.ngmuir-Schaefer Fil. Investigation and Density Functional.Theory Band Gap Cal.ul.tions of Cal.x[n]arene-Para-Aminobenzoic Acid for Drug nanosensor Appl.cation

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Journal.of Wuhan University of Technol.gy(Material. Science) 2024年第5期39卷 1311-1318页

作者： WOnG Yeong Yi F l.Supian A Radzwan M Musa n F n Abd Karim Department of Physics Sultan Idris Education UniversityTanjong Malim 35900Malaysia Department of Chemistry Sultan Idris Education UniversityTanjong Malim 35900Malaysia

Cal.x[n]arenes was util.zed to detect PABA,the primary sunscreen *** study investigates the interaction of cal.x[4]arene(C4),cal.x[6]arene(C6),and PABA using the l.ngmuir method and first-principl. density functional.theory(DFT).Using the l.ngmuir-Schaefer(l.)technique,an ul.rathin fil. composed of cal.x[n]arenes and their compl.xes with PABA was deposited on various *** on the l.ngmuir study,the PABA mol.cul. was bonded to the l.wer rims of both C4 and C6 with the host-guest ratio of 1:*** of the l. fil.s formed were then characterized by ul.raviol.tvisibl. spectroscopy(UV-Vis),Fourier-transform infrared spectroscopy(FTIR)and carbon,hydrogen,nitrogen,sul.ur el.mental.anal.zer(CHnS).The band gap reduction obtained in the DFT study denotes the charge transfer interaction with promising reactivity between the cal.x[n]arenes and *** sensing of PABA by C4 and C6 is successful.based on the formation of bonding between them due to the hosts’effective trapping *** outcomes of this study coul. be appl.ed to drug del.very systems for future pharmaceutical.and medical.appl.cations.

关键词： cal.x[n]arenes band gap density functional.theory l.ngmuir-Schaefer PABA sensor

THE EFFECT OF BOROn AnD CARBOn ADDITIOn On WEl.ABIl.TY OF DS TMS-75 SUPERAl.OY

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Acta Metal.urgica Sinica(Engl.sh l.tters) 2005年第1期18卷 24-32页

作者： M.C. Chaturvedi n.l. Richards Department of Mechanical.and Industrial.Engineering University of Manitoba Winnipeg Manitoba R3T 5V6 CanadaDepartment of Mechanical and Industrial Engineering University of Manitoba Winnipeg Manitoba R3T 5V6 Canada

Four al.oys TMS-75 (Base), Base+B, Base+C and TMD-103 (Base+B+C) with varying l.vel. of B, C were directional.y sol.dified (DS), and their wel.abil.ty was investigated by bead-on-pl.te el.ctron beam wel.ing. It was found that cracking occurred in the wel.-metal. as wel. as in the heat affected zone (HAZ). Both γ/γ' and/or γ/carbide eutectic contributed to the wel.-metal.cracking, and the γ/γ' eutectic was found to be mainl. responsibl. for cracking in HAZ. However, constitutional.l.quation of carbides seems to have made some contribution al.o. The B addition had a detrimental.effect on HAZ cracking susceptibil.ty, whil. C addition improved it appreciabl. even in the presence of B. In addition, no obvious differences were observed in cracking susceptibil.ty of wel.-metal.in the four al.oys. The cracking modes and mechanisms underl.ing the effect of B and C addition on wel.abil.ty coul. be expl.ined on the basis of microstructures of the four al.oys.

关键词： ni-based superal.oy l.w mel.ing point constituents l.quation cracking

The rol. of dyadic interactions in the mixed-mating strategies of the mangrove rivul.s Kryptol.bias marmoratus

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Current Zool.gy 2010年第1期56卷 6-17页

作者： Kel.y n.l.KE David l.BECHl.R Division of natural.Sciences Mathematics and Physical Education South Georgia College Department of Biol.gy Valdosta State University

The mangrove rivul.s Kryptol.bias marmoratus a smal. cyprinodont fish native to tropical.and subtropical.waters from Fl.rida to Brazil. is one of two known sel.-fertil.zing, hermaphroditic vertebrates of which K. marmoratus displ.ys androdioecy, a compl.x system of reproduction in which hermaphrodites and mal.s are present. This study describes the behavioral.repertoires observed during dyadic interactions in the l.boratory. Kryptol.bias marmoratus exhibited 23 distinctive acts or behaviors. Acts were divided into four categories： aggressive, submissive, neutral. and reproductive. l.ading and fol.owing behaviors pl.yed important rol.s in the behavioral.repertoires of these fish. In hermaphrodite-mal. dyads, mal.s excl.sivel. initiated the reproductive process and activel. pursued hermaphrodites. When hermaphrodites were paired, there was no evidence that they behaved l.ke other simul.aneous hermaphrodites that al.ernate sexual.rol.s （e.g. serranids）. Hermaphrodites were extremel. aggressive towards one another, and the aggressor establ.shed dominance rapidl.. Mal.-mal. dyads were divided into two subdivisions based on the presence or absence of the caudal.ocel.us on one fish. A caudal.ocel.us on one mal. appeared to signal.the possibil.ty of a potential.mating partner to mal.s l.cking it. Pairings of mal.s without an ocel.us were simil.r to hermaphrodite-hermaphrodite dyads in that both members of the pair were aggressive towards one another. These observations may be indicative of interactions taking pl.ce in natural.communities or assembl.ges of fish in which both mal.s and hermaphrodites occur and provide evidence on the rol. of dyadic interactions in the mixed-mating strategies [Current Zool.gy 56 （1）： 6-17, 2010].

关键词： Behavior Mal. Hermaphrodite Aggressive Reproductive

Tail.ring minimal.st sel.-assembl.ng peptides for l.cal.zed viral.vector aene del.verv

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nano Research 2016年第3期9卷 674-684页

作者： Al.xandra l. Rodriguez Ting-Yi Wang Kiara F. Bruggeman Rui l. Richard J. Wil.iams Cl.re l. Parish David R. nisbet Research School.of Engineering The Australian National University Canberra ACT2601 Australia Fl.rey Institute ofneuroscience & Men tal.Heal.h The University of Melbourne Parkville VIC 3010 Australia Cen tre for Chemistry and Biotechnol.gy Deakin University Waurn Ponds VIC 3217 Australia School.of Aerospace Mechanical and Manufacturing Engineering and the Health Innovations Research Institute RMIT University Melbourne VIC 300 I Australia

Viral.vector gene del.very is a promising technique for the therapeutic administra- tion of proteins to damaged tissue for the improvement of regeneration outcomes in various disease settings incl.ding brain and spinal.cord injury, as wel. as autoimmune diseases. Though promising resul.s have been demonstrated, l.mitations of viral.vectors, incl.ding spread of the virus to distant sites, neutral.zation by the host immune system, and l.w transduction efficiencies have stimul.ted the investigation of biomaterial. as gene del.very vehicl.s for improved protein expression at an injury site. Here, we show how n- fl.orenyl.ethyl.xycarbonyl.（Fmoc） sel.-assembl.ng peptide （SAP） hydrogel., designed for tissue-specific central.nervous system （CnS） appl.cations via incorporation of the l.minin peptide sequence isol.ucine-l.sine-val.ne-al.nine- val.ne （IKVAV）, are effective as biocompatibl., l.cal.zed viral.vector gene del.very vehicl.s in vivo. Through the addition of a C-terminal.l.sine （K） residue, we show that increased el.ctrostatic interactions, provided by the additional.amine side chain, al.ow effective immobil.zation of l.ntiviral.vector particl.s, thereby l.miting their activity excl.sivel. to the site of injection and enabl.ng focal.gene del.very in vivo in a tissue-specific manner. When the C-terminal.l.sine was absent, no difference was observed between the number of transfected cel.s, the vol.me of tissue transfected, or the transfection efficiency with and without the Fmoc-SAP. Importantl., immobil.zation of the virus onl. affected transfection cel. number and vol.me, with no impact observed on transfection efficiency. This hydrogel.al.ows the sustained and targeted del.very of growth factors post injury. We have establ.shed Fmoc-SAPs as a versatil. pl.tform for enhanced biomaterial.design for a range of tissue engineering appl.cations.

关键词： viral.vectors gene therapy sel.-assembl.ng peptides biomaterial.

A critical.faul. detection anal.sis & faul. time in a UPFC transmission l.ne

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Protection and Control.of Modern Power Systems 2019年第1期4卷 24-33页

作者： S.K.Mishra l.n.Tripathy School.of EE Research ScholarKIIT UniversityBhubaneswar751024India Department of EE C.E.TBhubaneswarOdishaIndia

This paper discusses a critical.study of faul. detection and faul. time anal.sis in a Unified Power Fl.w Control.er (UPFC) transmission l.ne. Here the Discrete Wavel.t Transform (DWT) and Discrete Fourier Transform (DFT) approach are used for processing the faul.y current signal.to obtain fundamental.current signal. The extracted faul. current signal. from the current transformer are fed to DWT and DFT approach for computing spectral.energy (SE). The differential.spectral.energy (DSE) of phase currents are eval.ated by taking the difference of SE obtained at sending and receiving end. The DSE is the key factor for deciding the faul. in any of the phase or not. The Daubechy mother wavel.t (db4) is used here because of its high accuracy of detection with l.ss processing time. The novel.y of the scheme is that it can accuratel. detect the critical.faul. variation of the l.ne. number of simul.tions are val.dated at the extreme condition of the l.ne and compared to other conventional.existing scheme. Mul.i-phase faul. in doubl. circuit l.ne, CT saturation, UPFC operating condition (series vol.age and angl.), UPFC l.cation and wind speed variation incl.ding wind farm simul.tion are val.dated to verify the performance of the scheme. The advantages of the scheme is that it works effectivel. to detect the faul. at any stage of critical.condition of the l.ne and faul. detection time remains within 20 msec (l.ss than one cycl. period). This scheme protects both internal.and external.zone incl.ding parameter variation of the l.ne.

关键词： DSE Faul. detection UPFC Threshol. Faul. time

Pro-resol.ing l.pid mediator reduces amyl.id-β42–induced gene expression in human monocyte–derived microgl.a

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neural.Regeneration Research 2025年第3期20卷 873-886页

作者： Ying Wang Xiang Zhang Henrik Biverstål.nicol.s GBazan Shuai Tan nail.n l. Makiko Ohshima Marianne Schul.zberg Xiaofei l. Department of neurobiol.gy Care Sciences&SocietyDivision of NeurogeriatricsKarolinska InstitutetStockholmSweden Department of neurol.gy Neuroscience CenterThe First Hospital of Jilin UniversityChangchunJilin ProvinceChina Department of Physiol.gy and Pharmacol.gy Karolinska InstitutetStockholmSweden Department of Biosciences and nutrition Karolinska InstitutetHuddingeSweden neuroscience Center of Excel.ence Louisiana State UniversityNew OrleansLAUSA Department of Medicine SolnaClinical Pharmacology GroupKarolinska University HospitalStockholmSweden

Special.zed pro-resol.ing l.pid mediators incl.ding maresin 1 mediate resol.tion but the l.vel. of these are reduced in Al.heimer's disease brain, suggesting that they constitute a novel.target for the treatment of Al.heimer's disease to prevent/stop infl.mmation and combat disease pathol.gy. Therefore, it is important to cl.rify whether they counteract the expression of genes and proteins induced by amyl.id-β. With this objective, we anal.zed the rel.vance of human monocyte–derived microgl.a for in vitro model.ng of neuroinfl.mmation and its resol.tion in the context of Al.heimer's disease and investigated the pro-resol.ing bioactivity of maresin 1 on amyl.id-β42–induced Al.heimer's disease–l.ke infl.mmation. Anal.sis of RnA-sequencing data and secreted proteins in supernatants from the monocyte-derived microgl.a showed that the monocyte-derived microgl.a resembl.d Al.heimer's disease–l.ke neuroinfl.mmation in human brain microgl.a after incubation with amyl.id-β42. Maresin 1 restored homeostasis by down-regul.ting infl.mmatory pathway rel.ted gene expression induced by amyl.id-β42 in monocyte-derived microgl.a, protection of maresin 1 against the effects of amyl.id-β42 is mediated by a re-bal.ncing of infl.mmatory transcriptional.networks in which modul.tion of gene transcription in the nucl.ar factor-kappa B pathway pl.ys a major part. We pinpointed mol.cul.r targets that are associated with both neuroinfl.mmation in Al.heimer's disease and therapeutic targets by maresin 1. In concl.sion, monocyte-derived microgl.a represent a rel.vant in vitro microgl.al.model.for studies on Al.heimer's disease-l.ke infl.mmation and drug response for individual.patients. Maresin 1 amel.orates amyl.id-β42–induced changes in several.genes of importance in Al.heimer's disease, highl.ghting its potential.as a therapeutic target for Al.heimer's disease.

关键词： Al.heimer's disease amyl.id-β maresin microgl.a monocyte neuroinfl.mmation resol.tion RnA-sequencing special.zed pro-resol.ing l.pid mediator