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Signaling from T cell receptors (TCRs) and chimeric antigen receptors (CARs) on T cells

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Cellular & Molecular Immunology 2020年第6期17卷 600-612页

作者： Ling Wu Qianru Wei joanna Brzostek nicholas R.j.Gascoigne Department of Microbiology and Immunology Yong Loo Lin School of MedicineNational University of Singapore5 Science Drive 2Singapore 117545Singapore Immunology Programme Life Sciences InstituteNational University of SingaporeSingaporeSingapore

T cells react to foreign or self-antigens through T cell receptor(TCR)*** decades of research have delineated the mechanism of TCR signal transduction and its impact on T cell *** knowledge provides the foundation for chimeric antigen receptor T cell(CAR-T cell)technology,by which T cells are redirected in a major histocompatibility complex-unrestricted *** and CAR signaling plays a critical role in determining the T cell state,including exhaustion and *** its artificial nature,CARs might affect or rewire signaling differently than TCRs.A better understanding of CAR signal transduction would greatly facilitate improvements to CAR-T cell technology and advance its usefulness in clinical ***,we systematically review the knowns and unknowns of TCR and CAR signaling,from the contact of receptors and antigens,proximal signaling,immunological synapse formation,and late signaling *** through different T cell subtypes and how signaling is translated into practice are also discussed.

关键词： CAR-T TCR Signaling T cell Immunological synapse

Complex interactions between biota, landscapes and native peoples

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Ecological Processes 2013年第1期2卷 297-299页

作者： jose MV Fragoso nicholas j Reo Department of Biology Stanford UniversityStanfordCAUSA Environmental Studies Program Dartmouth CollegeHanoverNHUSA

The papers presented here originated with a symposium held at the Ecological Society of America’s annual meeting in Portland,Oregon,in *** describe how native people and indigenous researchers view and understand the cultural and biological complexity inherent in coupled socio-ecological *** researchers note that interactions between native peoples and their environments consist of a complex network of linkages,feedbacks,and change,and they describe synthetic approaches to problem *** approaches often spring from long cultural traditions and recent adaptations to *** are examples of native peoples successfully managing biota and ecosystems for thousands of ***,current societal conditions often challenge indigenous-based efforts to continue managing ecosystems and ***,in the face of the new challenges native people continue to innovate and manage their environments and biota.

关键词： continue environments landscape

Travellers:Design Collaboration and Digital Media

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Tsinghua Science and Technology 2008年第S1期13卷 234-240页

作者： j. Bahoric P. nicholas G. Ormston Arup Pty Ltd Spatial Information Architecture Laboratory RMIT University Melbourne 3000 Australia City of Melbourne

This paper examines the use of 3D electronic medium as a tool for procuring detailed design information for the Sandridge Bridge Travellers project. The Sandridge Bridge Travellers project required the production of 10 7.5 m of tall × 5 ― 12 m of wide figures under very tight programme and budget constraints. This was achieved through a synthesis of art and engineering, whereby structure and sculpture become one and the same. Traditional procurement routes would have entailed the production and interpretation of drawings and design details at all discipline interfaces before fabrication; an approach that was unfeasible given the constraints. Instead, The Travellers project saw a single electronic file pass backwards and forwards from client to architect, engineer, and fabricator, with information from the initial artistic concept work phases through to analysis, design, member scheduling and fabrication all integrated and facilitated by a single electronic medium. Key to the delivery was the use of 3D modeling and scripting programs that enabled the efficient use and development of design information through all stages of the design process. This enabled total integration of all trades requiring a collaborative approach where each party maintained joint ownership of the 3D design information from inception to conception.

关键词： Sandridge Bridge Travellers sculpture 3-D modeling collaborative approach 3-D electronic medium AutoCAD R2004TM RhinoTM formats spline rationalization

Acid and non-acid reflux in patients refractory to proton pump inhibitor therapy:Is gastroparesis a factor?

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World journal of Gastroenterology 2013年第37期19卷 6193-6198页

作者： Anna Tavakkoli Bisma A Sayed nicholas j Talley Baharak Moshiree Department of Medicine Columbia University Medical Center Department of Sociology University of Miami Faculty of Health University of Newcastle Department of Gastroenterology University of Miami

AIM:To determine whether an increased number and duration of non-acid reflux events as measured using the multichannel intraluminal impedance pH(MII-pH)is linked to gastroparesis(GP).METHODS:A case control study was conducted in which 42 patients undergoing clinical evaluation for continued symptoms of gastroesophageal reflux disease(both typical and atypical symptoms)despite acid suppression ***-pH technology was used over 24 h to detect reflux episodes and record patients’*** evaluated in patients with documented GP and controls without GP by scintigraphy included total,upright,and supine number of acid and non-acid reflux episodes(pH4,respectively),the duration of acid and non-acid reflux in a 24-h period,and the number of reflux episodes lasting longer than 5 ***:No statistical difference was seen between the patients with GP and controls with respect to the total number or duration of acid reflux events,total number and duration of non-acid reflux events or the duration of longest reflux *** number of nonacid reflux episodes with a pH>7 was higher in subjects with GP than in *** addition,acid reflux episodes were more prolonged(lasting longer than 5min)in the GP patients than in controls;however,these values did not reach statistical ***-five patients had recorded symptoms during the 24 h study and of the 35 subjects,only 9%(n=3)had a positive symptom association probability(SAP)for acid/non-acid reflux and 91%had a negative ***:The evaluation of patients with a documented history of GP did not show an association between GP and more frequent episodes of non-acid reflux based on MII-pH testing.

关键词： Gastroparesis Non-acid gastroesophageal reflux Acid gastroesophageal reflux Multi-channel intraluminal impedance Functional bowel disorder

Softening of phonon spectra in metallic glasses

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npj Computational Materials 2016年第1期2卷 31-35页

作者： Reza Mahjoub nicholas E Hamilton Kevin j Laws Michael Ferry School of Materials Science and Engineering The University of New South WalesSydneyNSWAustralia

The vibrational spectra of a series of MgZnCa amorphous alloys were computed using density functional theory and implementing the small displacement *** atomic structures of the alloys were obtained by ab initio molecular dynamics *** vibrational thermodynamic properties were calculated as a function of temperature and,in particular,the specific heat at low temperature was approximated by temperature cubed based on the Debye *** computed the contribution of Mg vibrations to the specific heat and investigated the softening of Mg phonon spectra,where the maximum allowed vibrational frequency is lowered and highly collective diffusion processes are *** statistical correlation between the reported critical casting thickness of the alloys and softening of Mg phonons was *** calculations were performed for two distinctively different amorphous ZrTiCuAl alloys with large and small reported critical casting thickness,*** findings were consistent with those of the MgZnCa alloys.

关键词： alloys softening casting

Seasonal resource selection of an arboreal habitatspecialist in a human-dominated landscape: A case studyusing red panda

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Current Zoology 2023年第1期69卷 1-11页

作者： Damber Bista Greg S.Baxter nicholas j.Hudson Peter j.Murray School of Agriculture and Food Sciences(Wildlife Science Unit) The University of QueenslandGattonQLD 4343Australia School of Agriculture and Environmental Science University of Southern QueenslandDarling HeightsQLD 4350Australia

Human-dominated landscapes provide heterogeneous wildlife habitat. Conservation of habitat specialists, like red pandas Ailurus fulgens, inhabiting such landscapes is challenging. Therefore, information on resource use across spatial and temporal scales could enable informed-decisionmaking with better conservation outcomes. We aimed to examine the effect of geo-physical, vegetation, and disturbance variables on fine-scalehabitat selection of red pandas in one such landscape. We equipped 10 red pandas with GPS collars in eastern Nepal in 2019 and monitoredthem for 1 year. Our analysis was based on a generalized-linear-mixed model. We found the combined effect of geo-physical, vegetation, anddisturbance variables resulted in differences in resource selection of red pandas and that the degree of response to these variables variedacross seasons. Human disturbances, especially road and cattle herding activities, affected habitat utilization throughout the year whereas othervariables were important only during restricted periods. For instance, geo-physical variables were influential in the premating and cub-rearingseasons while vegetation variables were important in all seasons other than premating. Red pandas selected steeper slopes with high solarinsolation in the premating season while they occupied elevated areas and preferred specific aspects in the cub-rearing season. Furthermore,the utilized areas had tall bamboo in the birthing and cub-rearing seasons while they also preferred diverse tree species and high shrub coverin the latter. Our study demonstrates the significance of season-specific management, suggests the importance of specific types of vegetationduring biologically crucial periods, and emphasizes the necessity to minimize disturbances throughout the year.

关键词： Ailurus fulgens anthropogenic disturbances habitat specialists habitat utilization resource use spatio-temporal variation vegetation

Visualising the heart of chaos

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Light(Science & Applications) 2021年第12期10卷 2256-2257页

作者： nicholas j.Lambert Harald G.L.Schwefel Department of Physics University of OtagoDunedinNew Zealand The Dodd-Walls Centre for Photonic and Quantum Technologies DunedinNew Zealand

The intra-cavity electro-magnetic field distribution in a microdisk resonator can be visualised by inducing a phase shift via a scanning probe beam.

关键词： resonator chaos Visual

100pT/cm single-point MEMS magnetic gradiometer from a commercial accelerometer

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Microsystems & Nanoengineering 2020年第1期6卷 602-614页

作者： josh javor Alexander Stange Corey Pollock nicholas Fuhr David j.Bishop Department of Mechanical Engineering Boston UniversityBostonMA 02215USA Division of Materials Science and Engineering Boston UniversityBostonMA 02215USA Department of Electrical and Computer Engineering Boston UniversityBostonMA 02215USA Department of Physics Boston UniversityBostonMA 02215USA Department of Biomedical Engineering Boston UniversityBostonMA 02215USA

Magnetic sensing is present in our everyday interactions with consumer electronics and demonstrates the potential for the measurement of extremely weak biomagnetic fields,such as those of the heart and *** this work,we leverage the many benefits of microelectromechanical system(MEMS)devices to fabricate a small,low-power,and inexpensive sensor whose resolution is in the range of biomagnetic *** present,biomagnetic fields are measured only by expensive mechanisms such as optical pumping and superconducting quantum interference devices(SQUIDs),suggesting a large opportunity for MEMS technology in this *** prototype fabrication is achieved by assembling micro-objects,including a permanent micromagnet,onto a postrelease commercial MEMS accelerometer using a pick-and-place *** this system,we demonstrate a room-temperature MEMS magnetic *** air,the sensor’s response is linear,with a resolution of 1.1 nT cm^(−1),spans over 3 decades of dynamic range to 4.6µT cm^(−1),and is capable of off-resonance measurements at low *** a 1mTorr vacuum with 20 dB magnetic shielding,the sensor achieves a 100 pT cm^(−1) resolution at *** resolution represents a 30-fold improvement compared with that of MEMS magnetometer technology and a 1000-fold improvement compared with that of MEMS gradiometer *** sensor is capable of a small spatial resolution with a magnetic sensing element of 0.25 mm along its sensitive axis,a>4-fold improvement compared with that of MEMS gradiometer *** calculated noise floor of this platform is 110 fTcm^(−1) Hz−1/2,and thus,these devices hold promise for both magnetocardiography(MCG)and magnetoencephalography(MEG)applications.

关键词： accelerometer magnetometer everyday

Interference from HONO in the measurement of ambient air NO2 via photolytic conversion and quantification of NO

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journal of Environmental Sciences 2021年第9期33卷 184-193页

作者： nicholas j.Gingerysty Charles A.Odame-Ankrah Nick jordan Hans D.Osthoff Department of Chemistry University of CalgaryCalgary AB T2N 1N4Canada Global Analyzer Systems Ltd. Calgary AB T2E 7L6Canada

The reference method to quantify mixing ratios of the criteria air pollutant nitrogen dioxide(NO_(2)) is NO-O_(3) chemiluminescence(CL), in which mixing ratios of nitric oxide(NO) are measured by sampling ambient air directly, and mixing ratios of NO_(x)(= sum of NO and NO_(2))are measured by converting NO_(2) to NO using, for example, heated molybdenum catalyst or,more selectively, photolytic conversion(P-CL).In this work, the nitrous acid(HONO) interference in the measurement of NO_(2) by P-CL was *** with two photolytic NO2 converters are *** first used radiation centered at 395 nm, a wavelength region commonly utilized in *** second used light at 415 nm, where the overlap with the HONO absorption spectrum and hence its photolysis rate are *** ratios of NO_(2),NO_(x) and HONO entering and exiting the converters were quantified by Thermal Dissociation Cavity Ring-down Spectroscopy(TD-CRDS).Both converters exhibited high NO_(2) conversion efficiency(CF_(NO2);> 90%) and partial conversion of *** of CF against flow rate were consistent with photolysis frequencies of 4.2 s^(-1) and 2.9 s^(-1) for NO_(2) and 0.25 s^(-1) and 0.10 s^(-1) for HONO at 395 nm and 415 nm, *** larger than predicted from the overlap of the emission and HONO absorption *** results imply that measurements of NO2 by P-CL marginally but systematically overestimate true NO_(2) concentrations,and that this interference should be considered in environments with high HONO:NO_(2) ratios such as the marine boundary layer or in biomass burning plumes.

关键词： Photolytic conversion of NO_(2) HONO interference