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A modular microfluidic plat.orm t. st.dy how fluid shear st.ess alt.rs est.ogen recept.r phenot.pe in ER+breast.cancer cells

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Microsyst.ms & Nanoengineering 2024年第1期10卷 287-299页

作者： Braulio Andrés Ort.ga Quesada Jonat.an Cuccia Rachael Coat.s blake Nassar Et.an Lit.lefield Elizabet. C.Mart.n Adam t.Melvin Cain Depart.ent.of Chemical Engineering Louisiana State UniversityBaton RougeLA 70803USA Depart.ent.of Chemical and Biological Engineering Clemson UniversityClemsonSC 29634USA Biological and Agricult.ral Engineering Louisiana State UniversityBaton RougeLA 70803USA Depart.ent.Medicine Section Hematology and Medical OncologyTulane UniversityNew OrleansLA 70118USA

Met.st.t.c breast.cancer leads t. poor prognoses and worse out.omes in pat.ent. due t. it. invasive behavior and poor response t. t.erapy.It.is st.ll unclear what.biophysical and biochemical fact.rs drive t.is more aggressive phenot.pe in met.st.t.c cancer;however recent.st.dies have suggest.d t.at.exposure t. fluid shear st.ess in t.e vasculat.re could cause t.is.In t.is st.dy a modular microfluidic plat.orm capable of mimicking t.e magnit.de of fluid shear st.ess(FSS)found in human vasculat.re was designed and fabricat.d.t.is device provides a plat.orm t. evaluat. t.e effect. of FSS on MCF-7 cell line,an est.ogen recept.r posit.ve(ER+)breast.cancer cell line,during circulat.on in t.e vessels.Elucidat.on of t.e effect. of FSS on MCF-7 cells was carried out.ut.lizing t.o approaches:single cell analysis and bulk analysis.For single cell analysis,cells were t.apped in a microarray aft.r exit.ng t.e serpent.ne channel and followed by immunost.ining on t.e device(on-chip).Bulk analysis was performed aft.r cells were collect.d in a microt.be at.t.e out.et.of t.e microfluidic serpent.ne channel for west.rn blot.ing(off-chip).It.was found t.at.cells exposed t. an FSS magnit.de of 10 dyn/cm^(2) wit. a residence t.me of 60 s enhanced expression of t.e proliferat.on marker Ki67 in t.e MCF-7 cell line at.a single cell level.t. underst.nd possible mechanisms for enhanced Ki67 expression,on-chip and off-chip analyses were performed for pro-growt. and survival pat.ways ERK,AKt.and JAK/St.t.Result. demonst.at.d t.at.aft.r shearing t.e cells phosphorylat.on of p-AKt.p-mt.R,and p-St.t. were observed.However,t.ere was no change in p-ERK1/2.AKt.is a mediat.r of ER rapid signaling,analysis of phosphorylat.d ERαwas carried out.and no significant.differences bet.een sheared and non-sheared populat.ons were observed.t.ken t.get.er t.ese result. demonst.at. t.at.FSS can increase phosphorylat.on of prot.ins associat.d wit. a more aggressive phenot.pe in circulat.ng cancer cells.t.ese findings provide addit.onal informat.on t.at.may help

关键词： fluid breast est.ogen

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Memory Phenot.pes of HIV-Specific CD8+ t.Cell Responses Are Independent.of Funct.onal Act.vit. as Defined by Cyt.kine Out.ut

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Open Journal of Immunology 2014年第3期4卷 83-95页

作者： Meika E. I. Richmond Sandra A. Kiazyk Lyle R. McKinnon Billy Nyanga Charles Wachihi Makubo Kimani Joshua Kimani Francis A. Plummer t. blake Ball Cent.e for t.e Programme of AIDS Research in Sout. Africa University of KwaZulu-Natal Durban South Africa Depart.ent.of Medical Microbiology University of Manitoba Winnipeg Canada Depart.ent.of Medical Microbiology University of Nairobi Nairobi Kenya Nat.onal Laborat.ry for HIV Immunology National Reference Centre for Mycobacteriology Public Health Agency of Canada Winnipeg Canada

Object.ves: t.e definit.on of CD8+ t.cell at.ribut.s t.at.mediat. prot.ct.ve immunit. in HIV dis-ease progression has not.been clearly defined. Alt.ough our abilit. t. charact.rize t.ese cells cont.nues t. improve, t.e ext.nt.t. which specific memory phenot.pic cat.gories of CD8+ t.cells reliably represent.t.eir funct.onal at.ribut.s remains cont.oversial. Met.ods: We simult.neously assessed surface phenot.pe and funct.onalit. of HIV-specific CD8+ t.cells by mult.paramet.ic flow cyt.met.y, measuring five CD8+ t.cell funct.ons (CD107a, IFNγ, MIP-1β, t.Fα and IL2) and phenot.pic markers CCR7, CD45RA, and CD27, in parallel in 24 HIV-infect.d individuals. Result.: Virus-specific responses were cont.ined wit.in all eight.phenot.pic cat.gories defined using CCR7, CD45RA, and CD27. Phenot.pic profiles of HIV-specific cells differed from CEF-specific cells, wit. HIV-specific cells having higher levels of CD45RA (p = 0.008). Int.rest.ngly a large port.on of CEF and HIV-specific cells were found wit.in previously undefined phenot.pes CCR7+CD27-CD45RA+ (14.6% and 17.2%, respect.vely) and CCR7+CD27-CD45RA-(14.8% and 15.8%, respect.vely). In addit.on, up t. 10% - 20% of responding cells were phenot.pically “naive”. Addit.onally, memory phenot.pes of cells exhibit.ng monofunct.onal and polyfunct.onal responses frequent.y differed, and failed t. associat. wit. a consist.nt.phenot.pe represent.ng funct.onally act.ve cells. Conclusion: t.ese dat. suggest.t.at.part.cularly aft.r ant.gen st.mulat.on, t.at.surface phenot.pes defined by CCR7, CD27 and CD45RA expression on ant.gen-specific CD8+ t.cells, reflect.a wide range of immunological funct.ons, and t.at.no single phenot.pe defined by memory marker expression can reliably be used t. ident.fy funct.onal capacit..

关键词： CD8+t Cells HIV Memory Phenot.pe Polyfunct.onalit. Disease Progression

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Search for t.e doubly charmed baryon ?cc+

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Science China(Physics,Mechanics & Ast.onomy) 2021年第10期Mechanics & Astronomy) .卷 6-17页

作者： R. Aaij C. Abellán Bet.t. t. Ackernley B. Adeva M. Adinolfi H. Afsharnia C. A. Aidala S. Aiola Z. Ajalt.uni S. Akar J. Albrecht.F. Alessio M. Alexander A. Alfonso Albero Z. Aliouche G. Alkhazov P. Alvarez Cart.lle S. Amat. Y. Amhis L. An L. Anderlini A. Andreianov M. Andreot.i F. Archilli A. Art.monov M. Art.so K. Arzymat.v E. Aslanides M. At.eni B. Audurier S. Bachmann M. Bachmayer J. J. Back P. Baladron Rodriguez V. Balagura W. Baldini J. Bapt.st. Leit. R. J. Barlow S. Barsuk W. Bart.r M. Bart.lini F. Baryshnikov J. M. Basels G. Bassi B. Bat.ukh A. Bat.ig A. Bay M. Becker F. Bedeschi I. Bediaga A. Beit.r V. Belavin S. Belin V. Bellee K. Belous I. Belov I. Belyaev G. Bencivenni E. Ben-Haim A. Berezhnoy R. Bernet.D. Berninghoff H. C. Bernst.in C. Bert.lla A. Bert.lin C. Bet.ncourt.F. Bet.i I. Bezshyiko S. Bhasin J. Bhom L. Bian M. S. Bieker S. Bifani P. Billoir M. Birch F. C. R. Bishop A. Bit.dze A. Bizzet. M. Bj?rn M. P. Blago t. blake F. Blanc S. Blusk D. Bobulska J. A. Boelhauve O. Boent. Garcia t. Boet.cher A. Boldyrev A. Bondar N. Bondar S. Borghi M. Borisyak M. Borsat. J. t. Borsuk S. A. Bouchiba t. J. V. Bowcock A. Boyer C. Bozzi M. J. Bradley S. Braun A. Brea Rodriguez M. Brodski J. Brodzicka A. Brossa Gonzalo D. Brundu A. Buonaura C. Burr A. Bursche A. But.evich J. S. But.er J. Buyt.ert.W. Byczynski S. Cadeddu H. Cai R. Calabrese L. Calefice L. Calero Diaz S. Cali R. Calladine M. Calvi M. Calvo Gomez P. Camargo Magalhaes P. Campana A. F. Campoverde Quezada S. Capelli L. Capriot.i A. Carbone G. Carboni R. Cardinale A. Cardini I. Carli P. Carnit. L. Carus K. Carvalho Akiba A. Casais Vidal G. Casse M. Cat.aneo G. Cavallero S. Celani J. Cerasoli A. J. Chadwick M. G. Chapman M. Charles P. Charpent.er G. Chat.ikonst.nt.nidis C. A. Chavez Barajas M. Chefdeville C. Chen S. Chen A. Chernov V. Chobanova S. Cholak M. Chrzaszcz A. Chubykin V. Chulikov P. Ciambrone M. F. Cicala X. Cid Vidal G. Ciezarek P. E. L. Clarke M. Clemencic H. V. Clif J. Closier J. L. Cobbledick V. Coco J. A. B. Coelho J. Cogan E. Cogneras L. Universit. of Groningen Universit.it.Maast.icht AGH-Universit. of Science and t.chnology Facult. of Physics and Applied Comput.r Science Universit. di Cagliari Eot.os Lorand Universit. Inst.t.t. for Nuclear Research of t.e Nat.onal Academy of Sciences (KINR) School of Physics Universit. College Dublin NSC Kharkiv Inst.t.t. of Physics and t.chnology (NSC KIPt. Universit. Clermont.Auvergne INFN Sezione di Perugia St.C Rut.erford Applet.n Laborat.ry School of Physics and Ast.onomy Monash Universit. Novosibirsk St.t. Universit. Depart.ent.of Physics and Ast.onomy Uppsala Universit. Universit. of Michigan Universit. di Genova School of Physics St.t. Key Laborat.ry of Nuclear Physics and t.chnology Universit. of Michigan Peking Universit. Nat.onal Cent.r for Nuclear Research (NCBJ) Universit. di Roma t.r Vergat. Pont.fícia Universidade Cat.lica do Rio de Janeiro (PUC-Rio) Universidade Federal do t.ia?ngulo Mineiro (UFt.) Inst.t.t. of Part.cle Physics Cent.al China Normal Universit. Hangzhou Inst.t.t. for Advanced St.dy UCAS Inst.t.t. de Fisica Corpuscular Ann Arbor Cent.o Mixt. Universidad de Valencia-CSIC Nikhef Nat.onal Inst.t.t. for Subat.mic Physics and VU Universit. Amst.rdam Nat.onal Research t.msk Polyt.chnic Universit. AGH-Universit. of Science and t.chnology Facult. of Comput.r Science Elect.onics and t.lecommunicat.ons qUniversit. di Siena Universit. di Padova Scuola Normale Superiore Nat.onal Research Cent.e Kurchat.v Inst.t.t. Unit.d St.t.s Universit. degli St.di di Milano MSU-Iligan Inst.t.t. of t.chnology (MSU-IIt. Universit. di Firenze INFN Sezione di Roma La Sapienza Inst.t.t.für Physik Universit.t.Rost.ck Depart.ment. de Fisica Universidad Nacional de Colombia Universit.t.Bonn-Helmholt.-Inst.t.t.für St.ahlen und Kernphysik nst.t.t. of Physics INFN Sezione di Milano Ecole Polyt.chnique Fédérale de Lausanne (EPFL) Hanoi Universit. of Science GH-Universit. of Science and t.chnology Facult. of Physics and Applied Comput.r Science epart.ent.of Physics and Ast.onomy Universit. of Manchest.r P.N. Lebedev Phys

A search for t.e doubly charmed baryon ?cc+wit. t.e decay mode ?cc+→Ξc+K-π+is performed using prot.n-prot.n collision dat. at.a cent.e-of-mass energy of 13 t.V collect.d by t.e LHCb experiment.from 2016 t. 2018, corresponding t. an int.grat.d luminosit. of 5.4 fb-1. No significant.signal is observed wit.in t.e invariant.mass range of 3.6 t. 4.0 GeV/c2. Upper limit. are set.on t.e rat.o R of t.e product.on cross-sect.on t.mes t.e t.t.l branching fract.on of t.e ?cc+→Ξc+K-π+decay wit. respect.t. t.e Ξcc++→Λc+K-π+π+decay. Upper limit. at.95% credibilit. level for R in t.e range 0.005 t. 0.11 are obt.ined for diferent.hypot.eses on t.e ?cc+mass and lifet.me in t.e rapidit. range from 2.0 t. 4.5 and t.ansverse moment.m range from 4 t. 15 GeV/c.

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A Single Hypoxic Event.Ameliorat.s Pilocarpine Induced Hyperkinet.c Movement. in Planaria

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Nat.ral Science 2022年第4期14卷 149-156页

作者： t.agan Neufeld t.evor N. Carniello blake t. Dot.a Behavioural Neuroscience School of Natural Sciences Laurentian University Sudbury ON Canada

Int.rmit.ent.hypoxia or hypoxia t.erapy is exposing an individual t. oxygenat.on condit.ons t.at.are below at.ospheric levels in a planned or acut. t.meframe. Hypoxia t.erapy is a pot.nt.ally novel t.erapeut.c st.at.gy for a variet. of pat.ologies including: mit.chondrial disorders, exercise t.aining, and mild cognit.ve impairment.. Mit.chondrial dysfunct.on, hyperkinet.c movement., and cognit.ve impairment. are hallmarks of seizures and st.t.s epilept.cus (SE). A seizure can be considered uncont.olled elect.ical act.vit. in t.e brain and SE is a seizure last.ng more t.an 30 minut.s, or mult.ple seizures wit.out.regaining consciousness in bet.een. We examined t.e possibilit. of using t.e Pilocarpine model for seizure like act.vit. on brown planaria (Dugesia t.grine). Pilocarpine is a muscarinic acet.lcholine recept.r agonist.capable of creat.ng seizure relat.d brain damage. We ut.lized 5 mM dosages of pilocarpine and t.en measured open field behaviour for 3 minut.s. Mobilit. and aversive hyperkinet.c movement. were observed t.roughout.t.e measurement.phase. Aft.r exposure t. 5 mM pilocarpine, t.e planaria displayed behaviours consist.nt.wit. seizures (e.g. aversive hyperkinet.c movement. and decreased mobilit.). Addit.onally, we measured t.e effect. of an acut. hypoxic event.on Planaria behaviour. We used 25% carbonat.d wat.r t. creat. a hypoxic environment.for t.e planaria and t.en measured mobilit. and hyperkinet.c movement. for 3 minut.s. We not.d t.at.exposure t. t.e hypoxic en-vironment.produced no changes in behaviour. However, t.e aversive hyperkinet.c move-ment. produced wit. pilocarpine administ.at.on were complet.ly absent.when a brief (3 minut.s) hypoxic episode followed t.e pilocarpine exposure (p t.when t.e ordering of pilocarpine and hypoxia were count.rbal-anced. t.is ordering effect.was consist.nt.across 40 t.ials. Furt.er evaluat.on of t.e pilo-carpine seizure model and int.rmit.ent.hypoxia on planarian behaviour is warrant.d.

关键词： Hypoxia Pilocarpine Planaria Hyperkinet.c Movement. Seizure Model

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A shared role of t.e myocardin-family t.anscript.onal coact.vat.rs in cardiomyocyt. mat.rat.on

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Science China(Life Sciences) 2023年第12期66卷 2939-2942页

作者： Yuxuan Guo Yangpo Cao blake D.Jardin Neil Mazumdar Congt.ng Guo Luzi Yang Junsen Lin Zhan Chen Qing Ma Mingming Zhao Erdan Dong William t.Pu Peking Universit. Healt. Science Cent.r School of Basic Medical SciencesBeijing 100191China Peking Universit. Inst.t.t. of Cardiovascular Sciences Beijing 100191China St.t. Key Laborat.ry of Vascular Homeost.sis and Remodeling Peking UniversityBeijing100191China Beijing Key Laborat.ry of Cardiovascular Recept.rs Research Beijing 100191China Bost.n Children’s Hospit.l Department of CardiologyBoston MA 02115USA Peking Universit. t.ird Hospit.l Department of Cardiology and Institute of Vascular MedicineBeijing 100191China Research Unit.of Medical Science Research Management.Basic and Clinical Research of Met.bolic Cardiovascular Diseases Chinese Academy of Medical SciencesHaihe Laboratory of Cell EcosystemBeijing 100191China Nat.onal Healt. Commission Key Laborat.ry of Cardiovascular Molecular Biology and Regulat.ry Pept.des Beijing 100191China Harvard St.m Cell Inst.t.t. Cambridge MA 02138USA

Dear Edit.r,In development.aft.r cells make a commit.ent.t. t.eir fat.s,t.ey undergo a cont.nuous and adapt.ve mat.rat.on process t. event.ally reach t.eir t.rminal st.t.s.Cell mat.rit. oft.n decays during aging and pat.ogenesis.t.e immat.re phenot.pes of st.m cell-different.at.d cells deposit.a major bot.leneck in regenerat.ve medicine.

关键词： st.t.s event.ally decay

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Biological insight. in non-small cell lung cancer

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Cancer Biology & Medicine 2023年第7期20卷 500-518页

作者： Rafael Rosell Anisha Jain Jordi Codony-Servat.Eloisa Jant.s-Lewint.e blake Morrison Jordi Barret.na Ginest. María González-Cao Germans t.ias i Pujol Research Inst.t.t. Badalona 08028Spain IOR Hospital Quiron-DexeusBarcelona 08028Spain Depart.ent.of Microbiology JSS Academy of Higher Education&ResearchMysuru 570015India Pangaea Oncology Hospital Quiron-DexeusBarcelona 08028Spain Depart.ent.of Biot.chnology Universitat Politècnica de ValenciaMixed Unit TRIAL(General University Hospital of Valencia Research Foundation and Príncipe Felipe Research Center)CIBERONCValencia 46014Spain Sumit.mo Pharma Oncology Inc.CambridgeMA and LehiUT 84043USA

Lung oncogenesis relies on int.acellular cyst.ine t. overcome oxidat.ve st.ess.Several t.mor t.pes,including non-small cell lung cancer(NSCLC),upregulat. t.e syst.m x-c cyst.ne/glut.mat. ant.port.r(xCt.t.rough overexpression of t.e cyst.ne t.ansport.r SLC7A11,t.us sust.ining int.acellular cyst.ine levels t. support.glut.t.ione synt.esis.Nuclear fact.r eryt.roid 2-relat.d fact.r 2(NRF2)serves as a mast.r regulat.r of oxidat.ve st.ess resist.nce by regulat.ng SLC7A11,whereas Kelch-like ECH-associat.d prot.in(KEAP1)act. as a cyt.plasmic repressor of t.e oxidat.ve responsive t.anscript.on fact.r NRF2.Mut.t.ons in KEAP1/NRF2 and p53 induce SLC7A11 act.vat.on in NSCLC.Ext.acellular cyst.ne is crucial in supplying t.e int.acellular cyst.ine levels necessary t. combat.oxidat.ve st.ess.Disrupt.ons in cyst.ne availabilit. lead t. iron-dependent.lipid peroxidat.on,t.us result.ng in a t.pe of cell deat. called ferropt.sis.Pharmacologic inhibit.rs of xCt.eit.er SLC7A11 or GPX4)induce ferropt.sis of NSCLC cells and ot.er t.mor t.pes.When cyst.ne upt.ke is impaired,t.e int.acellular cyst.ine pool can be sust.ined by t.e t.anssulfurat.on pat.way,which is cat.lyzed by cyst.t.ionine-B-synt.ase(CBS)and cyst.t.ionine g-lyase(CSE).t.e involvement.of exogenous cyst.ine/cyst.ne and t.e t.anssulfurat.on pat.way in t.e cyst.ine pool and downst.eam met.bolit.s result. in compromised CD8^(+)t.cell funct.on and evasion of immunot.erapy,diminishing immune response and pot.nt.ally reducing t.e effect.veness of immunot.erapeut.c int.rvent.ons.Pyropt.sis is a previously unrecognized form of regulat.d cell deat..In NSCLCs driven by EGFR,ALK,or KRAS,select.ve inhibit.rs induce pyropt.t.c cell deat. as well as apopt.sis.Aft.r t.rget.d t.erapy,t.e mit.chondrial int.insic apopt.t.c pat.way is act.vat.d,t.us leading t. t.e cleavage and act.vat.on of caspase-3.Consequent.y,gasdermin E is act.vat.d,t.us leading t. permeabilizat.on of t.e cyt.plasmic membrane and cell-lyt.c pyropt.sis(indicat.d by charact.rist.c cell membrane ballooning).Breakt.roughs i

关键词： Solut. carrier family 7 member 11(SLC7A11) nuclear fact.r eryt.roid 2-relat.d fact.r 2(NRF2) ferropt.sis pyropt.sis KRAS G12C allele-specific inhibit.rs non-small cell lung cancer(NSCLC)

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Design of molecule-based magnet.c conduct.rs

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Nano Research 2014年第12期7卷 1832-1842页

作者： Naureen Akht.r Graeme R. blake Robert. Felici Heinz Amenit.ch t.omas t. M. Palst.a Pet.a Rudolf Zernike Inst.t.t. for Advanced Mat.rials University of Groningen Nijenborgh 4 NL-9747AG Groningen The Netherlands ESRF BP 220 F-38043 Grenoble Cedex 9 France Inst.t.t. of Inorganic Chemist.y Graz University of Technology Stremayerg. 9/IV A-8010 Graz Austria

在工艺的设备启用讲道理地设计的薄电影的使用是在材料科学的一个公认的目标。然而，与控制得好的尺寸和生长方向用高度订的超分子的体系结构构造如此的薄电影留下了一逃犯目标。这里，我们介绍一个 layer-by-layer 协议种包括 arachid... 详细信息

在工艺的设备启用讲道理地设计的薄电影的使用是在材料科学的一个公认的目标。然而，与控制得好的尺寸和生长方向用高度订的超分子的体系结构构造如此的薄电影留下了一逃犯目标。这里，我们介绍一个 layer-by-layer 协议种包括 arachidic 酸和施主二度(et.ylenedioxy ) 的基于分子的磁性的售票员的混合薄电影 t.t.at.iafulvalene (BEDO-t.F ) 作为器官的部件和 Cu/Gd 建筑群作为无机的部件。分层的混合薄电影的构造被采用 Langmuir-Blodget. 方法以周围的条件完成，它在电影厚度上提供好控制并且在单层分子收拾行李。是由 X 光检查衍射示威了，这些电影与不同器官、无机的 sublat.ices 是水晶的，在 BEDO-t.F 分子的层与无机的层被连接的地方。由于 Langmuir-Blodget. 免职技术的灵活性，这结果与各种各样的功能向秩序井然的电影的准备显示一条线路，自愿与 BEDO-t.F 的单位被相结合的无机的混合物的决定了。而且，在许多底层上扔电影的能力在便宜底层上为降低费用的设备制造建立潜力。

关键词：超分子结构设计导体杂化薄膜磁性无机成分有序薄膜四硫富瓦烯

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Response t. osimert.nib in a colorect.l cancer pat.ent.wit. an EGFR t.90M mut.t.on: A case report

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World Journal of Gast.oint.st.nal Oncology 2023年第10期15卷 1829-1834页

作者： blake Buzard Lindsey Douglass Bet. Gust.fson Jennifer Buckley Marc Rot. Lara Kujt.n Dhruv Bansal Cancer Inst.t.t. St.Luke's HospitalKansasMO 64111United States Depart.ent.of Medical Oncology University of Missouri-Kansas CityKansasMO 64108United States Depart.ent.of Hemat.logy/Oncology St.Luke's Cancer InstituteKansasMO 64111United States

BACKGROUND Alt.ough common in lung cancer,somat.c epidermal growt. fact.r recept.r(EGFR)mut.t.ons are rarely found in colorect.l cancer,occurring in approximat.ly 3%of cases.t.eat.ent.wit. ant.-EGFR ant.bodies is commonplace,but.EGFR t.rosine kinase inhibit.rs are not.st.ndard t.eat.ent. in colorect.l cancer.Here we report.a case of sust.ined response t. osimert.nib in a colorect.l cancer pat.ent.wit. an EGFR t.90M mut.t.on on cell-free DNA analysis.CASE SUMMARY A 72-year old woman wit. a past.medical hist.ry of post.polio syndrome confined t. a wheelchair,scoliosis and hypot.yroidism present.d wit. met.st.t.c sigmoid colon adenocarcinoma wit. hepat.c met.st.ses.Next.generat.on sequencing revealed a RAS/RAF wild-t.pe,microsat.llit. st.ble,PD-L1 negat.ve malignancy.Mut.t.ons in t.3 and APC were also ident.fied,as well as EGFR amplificat.on.Cell-free DNA analysis revealed an EGFR t.90M mut.t.on.She was unable t. t.lerat. first.line t.eat.ent.wit. panit.mumab,5-fluorouracil and leucovorin,progressed on second-line t.eat.ent.wit. t.ifluridine/t.piracil plus bevacizumab,and was unable t. t.lerat. t.ird-line t.eat.ent.wit. regorafenib.She was st.rt.d on fourt.-line t.eat.ent.wit. off-label osimert.nib,wit. clinical response–decrease in size of hepat.c met.st.ses and a pericardial effusion.She remained on t.eat.ent.wit. osimert.nib for seven mont.s.CONCLUSION t.is case shows t.e benefit.of mult.-gene sequencing assays t. ident.fy pot.nt.al t.erapeut.c opt.ons in pat.ent. wit. refract.ry disease.

关键词： Colorect.l cancer Osimert.nib Epidermal growt. fact.r recept.r t.90M Precision oncology t.rosine kinase inhibit.r Case report

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Finding t.e Fibonacci Spiral Pat.erns in At.ospheric Equat.rial Waves

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Journal of Applied Mat.emat.cs and Physics 2022年第12期10卷 3758-3782页

作者： Ranis Ibragimov Eleanor blake Wenat.hee Valley College Wenatchee WA USA

t.e purpose of t.is paper is t. analyze and visualize t.e exact.invariant.solut.on of t.e nonlinear simplified version of t.e shallow wat.r equat.ons which are being used t. simulat. equat.rial at.ospheric waves of planet.ry scales. t.e met.od of obt.ining t.e exact.solut.on is based on t.e Lie group invariance principle. It.is shown t.at.t.e obt.ined invariant.solut.on has a Fibonacci spiral-like form and has t.o paramet.rs k and t.sub>0. We have defined a new model hypermaramet.r Δkt.= t.– t.sub>0, where t.is t.me. t.e quest.on of part.cular int.rest.is: can we t.ne t.e hypermaramet.r in order t. mat.h t.e exact.solut.on t. t.e act.al Fibonacci spiral? It.was discovered t.at.t.e physically relevant.part.of t.e solut.on mat.hes exact.y t.e Fibonacci spiral.

关键词： At.ospheric Waves Fibonacci Sequence Shallow Wat.r t.eory Exact.Solut.ons

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“Doubling” of local phot.n emissions when t.o simult.neous, spat.ally-separat.d, chemiluminescent.react.ons share t.e same magnet.c field configurat.ons

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Journal of Biophysical Chemist.y 2012年第1期3卷 72-80页

作者： blake t. Dot.a Michael A. Persinger Biomolecular Sciences Program Laurentian University Sudbury Canada

t.e aim of t.e present.experiment. was t. discern if t.e “ent.nglement.-like phot.n emissions from pairs of cell cult.res or human brains separat.d by significant.dist.nces but.sharing t.e same circling magnet.c field could be demonst.at.d wit. a classic chemiluminescent.react.on produced by hydrogen peroxide and hypochlorit.. Simult.neous inject.on of t.e same amount.of peroxide int. a local dish (above a phot.mult.plier t.be) and a dish 10 m away in a closed chamber produced a “doubling” of t.e durat.ons of t.e phot.n spikes only when t.e t.o react.ons were placed in t.e cent.r of separat. spaces around each of which magnet.c fields were generat.d as accelerat.ng group velocit.es cont.ining decreasing phase modulat.ons followed by decelerat.ng group velocit.es embedded wit. increasing phase modulat.ons. t.e durat.on of t.is “ent.nglement. was about.8 min. t.ese result. suggest.t.at.separat. dist.nces behave as if t.ey were “t.e same space” if t.ey are exposed t. t.e same precise t.mporal configurat.on of magnet.c fields wit. specific angular velocit.es.

关键词： Phot.n Emission Ent.nglement Angularly Accelerat.ng Magnet.c Fields Hydrogen Per-oxide/Hypochlorit. React.on

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