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Bridging the gap with multispecific immune cell engagers in cancer and infectious diseases

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Cellular & Molecular Immunology 2024年第7期21卷 643-661页

作者： Camille Rolin Jacques Zimmer carole Seguin-Devaux Department of Infection and Immunity Luxembourg Institute of Health29 Rue Henri KochL-4354 Esch-Sur-AlzetteLuxembourg.2University of Luxembourg Place de I'Universiteé L-4365 Esch-sur-AlzetteLuxembour

By binding to multiple antigens simultaneously,multispecific antibodies are expected to substantially improve both the activity and long-term efficacy of antibody-based *** cell engagers,a subclass of antibody-based constructs,consist of engineered structures designed to bridge immune effector cells to their target,thereby redirecting the immune response toward the tumor cells or infected *** increasing number of recent clinical trials evaluating immune cell engagers reflects the important role of these molecules in new therapeutic approaches for cancer and *** this review,we discuss how different immune cell types(T and natural killer lymphocytes,as well as myeloid cells)can be bound by immune cell engagers in immunotherapy for cancer and infectious ***,we explore the preclinical and clinical advancements of these constructs,and we discuss the challenges in translating the current knowledge from cancer to the virology ***,we speculate on the promising future directions that immune cell engagers may take in cancer treatment and antiviral therapy.

关键词： Immune cell engagers Multispecific antibodies Cancer Virus Immunotherapy

Delayed treatment of secondary degeneration following acute optic nerve transection using a combination of ion channel inhibitors

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Neural Regeneration Research 2017年第2期12卷 307-316页

作者： Nathanael J.Yates marcus K.Giacci Ryan l. O'Hare Doig Wissam Chiha Bethany E. Ashworth Jade Kenna carole A. Bartlett Melinda Fitzgerald Department of Experimental and Regenerative Neurosciences School of Animal Biology The University of Western Australia Crawley Western Australia Australia Department of Experimental and Regenerative Neurosciences School of Anatomy Physiology and Human Biology The University of Western Australia Crawley Western Australia Australia

Studies have shown that a combined application of several ion channel inhibitors immediately after central nervous system injury can inhibit secondary degeneration. However, for clinical use, it is necessary to determine how long after injury the combined treatment of several ion channel inhibitors can be delayed and efficacy maintained. In this study, we delivered Ca^2＋ entry-inhibiting P2X7 receptor antagonist oxidized-ATP and AMPA receptor antagonist YM872 to the optic nerve injury site via an iPRECIO-@ pump immediately, 6 hours, 24 hours and 7 days after partial optic nerve transection surgery. In addition, all of the ion channel inhibitor treated rats were administered with calcium channel antagonist lomerizine hydrochloride. It is important to note that as a result of implantation of the particular pumps required for programmable delivery of therapeutics directly to the injury site, seromas occurred in a significant proportion of animals, indicating infection around the pumps in these animals. Improvements in visual function were observed only when treatment was delayed by 6 hours; phosphorylated Tau was reduced when treatment was delayed by 24 hours or 7 days. Improvements in structure of node/paranode of Ranvier and reductions in oxidative stress indicators were also only observed when treatment was delayed for 6 hours, 24 hours, or 7 days. Benefits of ion channel inhibitors were only observed with time-delayed treatment, suggesting that delayed therapy of Ca^2＋ ion channel inhibitors produces better neuroprotective effects on secondary degeneration, at least in the presence of seromas.

关键词： nerve regeneration optic nerve injury neurotrauma secondary degeneration seromas calcium channel inhibitor node of Ranvier Tau phosphorylation lipid peroxidation oxidative stress neural regeneration

Muscle force and movement variability before and after total knee arthroplasty: A review

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World Journal of Orthopedics 2014年第2期5卷 69-79页

作者： Jessica W Smith Jesse C Christensen Robin l.marcus Paul C laStayo Department of Bioengineering University of Utah Salt Lake City UT 84108-1290 United States Department of Physical Therapy University of Utah Salt Lake City UT 84108-1290 United States Department of Orthopedics University of Utah Salt Lake City UT 84108-1290 United States Department of Exercise and Sport Science University of Utah Salt Lake City UT 84108-1290 United States

Variability in muscle force output and movement variability are important aspects of identifying individuals with mobility deficits, central nervous system impairments, and future risk of falling. This has been investigated in elderly healthy and impaired adults, as well as in adults with osteoarthritis(OA), but the question of whether the same correlations also apply to those who have undergone a surgical intervention such as total knee arthroplasty(TKA) is still being investigated. While there is a growing body of literature identifying potential rehabilitation targets for individuals who have undergone TKA, it is important to first understand the underlying post-operative impairments to more efficiently target functional deficits that may lead to improvedlong-term outcomes. The purpose of this article is to review the potential role of muscle force output and movement variability in TKA recipients. The narrative review relies on existing literature in elderly healthy and impaired individuals, as well as in those with OA before and following TKA. The variables that may predict longterm functional abilities and deficits are discussed in the context of existing literature in healthy older adults and older adults with OA and following TKA, as well as the role future research in this field may play in providing evidence-based data for improved rehabilitation targets.

关键词： Osteoarthritis Elderly Total knee arthroplasty Movement variability

Evaluating rock mass disturbance within open-pit excavations using seismic methods:A case study from the Hinkley Point C nuclear power station

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Journal of Rock Mechanics and Geotechnical Engineering 2021年第3期13卷 500-512页

作者： Antony Butcher Anna l.Stork James P.Verdon J-Michael Kendall Katrin Plenkers Finlay Booth marcus Boneham Adrian Koe School of Earth Sciences University of BristolWills Memorial BuildingQueen’s RoadBristolBS81RJUK Department of Earth Sciences University of OxfordSouth Parks RoadOxfordOX13ANUK Gesellschaft für Materialprüfung und Geophysik(GMuG) Bad Nauheim61231Germany Mott MacDonald 10 Temple BackBristolBS16FLUK Atkins The Hub500 Park AvenueAztec WestBristolBS324RZUK Atkins The Axis10 Holliday StreetBirminghamB11TFUK

Understanding rock strength is essential when undertaking major excavation projects,as accurate assessments ensure both safe and cost-effective engineered *** the cost-safety trade-off becomes more imperative during the construction of critical infrastructure such as nuclear power stations,where key components are built within relatively deep *** these engineered slopes is reliant on rock strength models,which are generally parameterised using estimates of rock properties(*** compressive strength,rock disturbance)measured prior to the commencement of ***,the physical process of excavation weakens the remaining rock ***,the model also requires an adjustment for the anticipated rock *** practice,this parameter is difficult to quantify and as a result it is often poorly *** can have a significant impact on the final design and cost of *** present results from passive and active seismic surveys,which image the extent and degree of disturbance within recently excavated slopes at the construction site of Hinkley Point C nuclear power *** from active seismic surveys indicate that the disturbance is primarily confined to 0.5 m from the excavated *** conjunction,passive monitoring is used to detected seismic events corresponding to fracturing on the cm-scale and event locations are in agreement with 0.5 m of disturbance into the rock *** suggests rock disturbance at this site is relatively low and occurred during and immediately after the excavation.A ratio of seismic velocities recorded before and after excavations are used to determine the disturbance parameter required for the Hoek eBrown rock failure criterion,and we assess that rock disturbance is low with the magnitude of the disturbance diminishing more quickly than expected into the excavated *** methods provide a low-cost and quick method to assess excavation related rock mass disturbance,

关键词： Rock mass strength Rock disturbance Seismic tomography Piezoelectric surveys Picoseismicity Acoustic emissions

Matched-pair analysis of postoperative morbidity and mortality for pancreaticogastrostomy and pancreaticojejunostomy using mattress sutures in soft pancreatic tissue remnants

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Hepatobiliary & Pancreatic Diseases International 2012年第1期11卷 89-95页

作者： Fritz Klein marcus Bahra Matthias Glanemann Wladimir Faber Peter Warnick Andreas Andreou Safak Gül Dietmar Jacob Department of General Visceraland Transplantation SurgeryCharité-Campus VirchowUniversit tsmedizin Berlin Department of Visceral Vascularand Minimally Invasive SurgeryVivantes Klinikum Spandau

BACKGROUND:After pancreaticoduodenectomy,the incidence of postoperative pancreatic fistula remains high,especially in patients with 'soft' pancreatic tissue *** 'gold standard' surgical technique for pancreaticoenteric anastomosis has been *** study aimed to compare the postoperative morbidity and mortality of pancreaticogastrostomy and pancreaticojejunostomy for 'soft' pancreatic tissue remnants using modified mattress ***:Seventy-five patients who had undergone pancreaticogastrostomy and 75 who had undergone pancreaticojejunostomy after pancreaticoduodenectomy between 2002 and 2008 were retrospectively compared using matched-pair analysis.A modified mattress suture technique was used for the pancreaticoenteric *** with an underlying 'hard' pancreatic tissue remnant,as in chronic pancreatitis,were *** groups were homogeneous for age,gender,and underlying *** morbidity,mortality,and preoperative and operative data were ***:There were no significant differences between the groups for the incidence of postoperative pancreatic fistula (10.7% in both).Postoperative morbidity and mortality,median operation time,median length of hospital stay,intraoperative blood loss,and the amount of intraoperatively transfused erythrocyte concentrates also did not significantly differ between the *** age >65 years (P=0.017),operation time >350minutes (P=0.001),and intraoperative transfusion of erythrocyte concentrates (P=0.038) were identified as risk factors for postoperative ***:Our results showed no significant differences between the groups in the pancreaticogastrostomy and pancreaticojejunostomy anastomosis techniques using mattress sutures for 'soft' pancreatic tissue *** our experience,the mattress sutures are safe and simple to use,and pancreaticogastrostomy in particular is feasible and easy to learn,with good endoscopic accessibility to the anastomos

关键词： mattress sutures pancreaticoduodenectomy pancreaticogastrostomy pancreaticojejunostomy soft pancreatic tissue remnant

Stigma Receptivity Is Controlled by Functionally Redundant MAPK Pathway Components in Arabidopsis

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Molecular Plant 2020年第11期13卷 1582-1593页

作者： Muhammad Jamshed Subramanian Sankaranarayanan Kumar Abhinandan marcus A.Samuel University of Calgary BI 392Department of Biological Sciences2500 University Dr.NWCalgaryAB T2N 1N4Canada Senior Scientist Frontier Agri-Science Inc98 Ontario StreetPort HopeON L1A2V2Canada Department of Botany and Plant Pathology Purdue UniversityWest LafayetteIN 47907USA

In angiosperms,the process of pollination relies on species-specific interaction and signaling between the male(pollen)and female(pistil)counterparts where the interplay between several pollen and stigma proteins decides the fate of the *** Brassicaceae,the dry stigmatic papillary cells control pollen germination by releasing resources only to compatible pollen thereby allowing pollen to hydrate and *** the identification of a number of stigmatic proteins that facilitate pollination responses,the signaling mechanisms that regulate functions of these proteins have remained ***,we show that,in Arabidopsis,an extremely functionally redundant mitogen-activated protein kinase(MAPK)cascade is required for maintaining stigma receptivity to accept compatible *** genetic analyses demonstrate that in stigmas,five MAPK kinases(MKKs),MKK1/2/3/7/9 are required to transmit upstream signals to two MPKs,MPK3/4,to mediate compatible *** functions of these five MKKs in the quintuple mutant(mkk1/2/3RNAi/mkk7/9)phenocopied pollination defects observed in the m pk4RNAi/m pk3 double *** further show that this MAPK nexus converges on Exo70A1,a previously identified stigma receptivity factor essential for *** that pollination is the crucial initial step during plant reproduction,understanding the mechanisms that govern successful pollination could lead to development of strategies to improve crop yield.

关键词： reproduction pollination stigma receptivity compatibility MAPK redundancy Exo70A1 exocytosis phosphorylation

Seed provenance determines germination responses of Rumex crispus (l.) under water stress and nutrient availability

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Journal of Plant Ecology 2019年第6期12卷 949-961页

作者： María Pérez-Fernández carole PElliott Alex Valentine JoséAntonio Oyola Ecology Area University Pablo de OlavideCarretera de Utrera Km 141013 SevillaSpain Kings Park Science Botanic Garden and Parks AuthorityDepartment of BiodiversityConservation and AttractionsKattidj CloseKings ParkWA 6005Australia School of Biological Science The University of Western AustraliaCrawleyWA 6009Australia Department of Botany and Zoology Stellenbosch UniversityPrivate Bag X1Matieland 7602South Africa Physics Department University of ExtremaduraAvenida de Elvas s/n06006 BadajozSpain

Aims Seeds of Rumex crispus from six provenances were studied in relation to their germination under drought and presence of nitrogen in the germination and emergence *** also investigated whether adaptation to soil increases the ability of the species to colonize and establish in contrasting environments along a longitudinal gradient in western Spain by means of a reciprocal transplantation *** We conducted a germination trial in the lab to test for the germination responses to water scarcity along a polyethylene glycol gradient and to varying concentrations of nitrogen *** reciprocal transplantations experiment was conducted,where seeds from six provenances were grown in the soils from the very same *** emergence,survivorship and fitness-related variables were measured in all *** Findings We found that *** has a cold-stratification requirement that enhances its *** differences between the six provenances were detected for time-to-germination,total seedling emergence,plant mortality and reproductive effort in all the *** differences between provenances with respect to germination were confirmed by the significant statistical analyses of the variance,thus providing evidence that seeds from parent plants grown in different environmental conditions have an intrinsically different abilities to germinate and *** nitrogen content where seed germination and seedlings establish also play an important role in their performance in terms of survivorship and reproduction,being the higher levels of inorganic nitrogen and of microbial biomass those that increased biomass production,enhanced inflorescence formation and reduced plant *** conclude that one of the main reasons for the spread and maintenance of *** would be the increased levels of nitrogen in agricultural soils.

关键词： seed provenance germination latitudinal gradient drought N-compounds soil properties

3D Nonlinear Numerical Simulation of Intact and Debonded Reinforced Concrete Beams

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Journal of Southwest Jiaotong University(English Edition) 2004年第2期12卷 173-177页

作者：陈权 marcus l. School of Computer and Communication Engineering Southwest Jiaotong University Department of Civil and Environment University of Southampton

To study the behaviour of reinforced concrete (RC) structures with sections of concrete removed and the reinforcement exposed, 3D nonlinear numerical analysis was performed upon both intact and debonded RC beams by using finite element techniques. The deformational characteristics and the ultimate loads were obtained through numerical models, as well as crack and stress distributions. The failure modes can also be deduced from computational results. Compared with intact beams, the normal assumptions of plane section behaviour is not hold true and the patterns of stress and strain are different in debonded RC beams. The numerical results show good consistency with experimental data. This kind of numerical simulation is a supplement to existing codes.

关键词： Finite element Reinforced concrete Nonlinear Ultimate load

Brain-derived neurotrophic factor rs6265(Val66Met)single nucleotide polymorphism as a master modifier of human pathophysiology

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Neural Regeneration Research 2023年第1期18卷 102-106页

作者： Van Thuan Nguyen Braxton Hill Naiya Sims Aaron Heck marcus Negron Claire lusk Cristi lGalindo Department of Biology Western Kentucky UniversityBowling GreenKYUSA

Brain-derived neurotrophic factor is the most prevalent member of the nerve growth factor *** its discovery in 1978,this enigmatic molecule has spawned more than 27,000 publications,most of which are focused on neurological ***-derived neurotrophic factor is indispensable during embryogenesis and postnatally for the normal development and function of both the central and peripheral nervous *** is becoming increasingly clear,however,that brain-derived neurotrophic factor likewise plays crucial roles in a variety of other biological functions independently of sympathetic or parasympathetic ***-derived neurotrophic factor is also increasingly recognized as a sophisticated environmental sensor and master coordinator of whole organismal *** that point,we recently found that a common nonsynonymous(Val66→Met)single nucleotide polymorphism in the brain-derived neurotrophic factor gene(rs6265)not only substantially alters basal cardiac transcriptomics in mice but subtly influences heart gene expression and function differentially in males and *** addition to a short description of recent results from associative neuropsychiatric studies,this review provides an eclectic assortment of research reports that support a modulatory role for rs6265 including and beyond the central nervous system.

关键词： brain-derived neurotrophic factor neuropsychiatric disorders rs6265 Val66Met