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multiparametric characterization of red blood cell physiology after hypotonic dialysis based drug encapsulation process

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Acta Pharmaceutica Sinica B 2022年第4期12卷 2089-2102页

作者： mélanie robert Bastien Laperrousaz Diana Piedrahita Emilie-Fleur Gautier Travis Nemkov Florian Dupuy Elie Nader Virginie Salnot Patrick mayeux Angelo D’Alessandro Catherine Lavazec Philippe Joly Alexander Scheer Philippe Connes Agnès Cibiel Erytech Pharma Lyon 69008France Laboratoire interuniversitaire de Biologie de la motricité(LIBm)EA7424 Team«Vascular Biology and Red Blood Cell»Universite´Claude Bernard Lyon 1Universite´de LyonLyon 69008France Labex GR-Ex Paris 75015France 3P5 proteom’IC facility Universitéde ParisInstitut CochinINSERMCNRSParis 75014France University of Colorado Anschutz Medical CampusAuroraCO 80045USA Omix Technologies Inc.AuroraCO 80045USA Inserm U1016 CNRS 8104Universitéde ParisInstitut CochinParis 75014France Laboratoire de Biochimie et de Biologie moléculaire UF de biochimie des pathologies e´rythrocytairesCentre de Biologie et de Pathologie EstHospices Civils de LyonBron 69500France

Red blood cells(RBCs)can act as carriers for therapeutic agents and can substantially improve the safety,pharmacokinetics,and pharmacodynamics of many *** RBCs integrity and lifespan is important for the efficacy of RBCs as drug *** investigated the impact of drug encapsulation by hypotonic dialysis on RBCs physiology and *** parameters were compared between processed RBCs loaded with l-asparaginase(“eryaspase”),processed RBCs without drug and non-processed *** RBCs were less hydrated and displayed a reduction of intracellular *** observed a change in the metabolomic but not in the proteomic profile of processed *** process caused moderate morphological changes and was accompanied by an increase of RBCs-derived Extracellular Vesicles *** a decrease in deformability,processed RBCs were not mechanically retained in a spleen-mimicking device and had increased surface-to-volume ratio and osmotic *** RBCs half-life was not significantly affected in a mouse model and our previous phase 1 clinical study showed that encapsulation of asparaginase in RBCs prolonged its in vivo half-life compared to free *** study demonstrated that encapsulation by hypotonic dialysis may affect certain characteristics of RBCs but does not significantly affect the in vivo longevity of RBCs or their drug carrier function.

关键词： Red blood cells Drug carrier Hypotonic dialysis L-Asparaginase Omics Rheology morphology Senescence markers

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Predicting the coefficient of friction in a sliding contact by applying machine learning to acoustic emission data

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Friction 2024年第6期12卷 1299-1321页

作者： robert GUTIERREZ Tianshi FANG robert mAINWARING Tom REDDYHOFF Tribology Group Department of Mechanical EngineeringImperial College LondonExhibition RoadLondon SW72AZUK Shell Global Solutions(US)Inc.Shell Technology Center Houston 3333 Highway 6 SouthHoustonTX 77082USA Shell International Petroleum Company Limited Shell CentreYork RoadLondon SE17NAUK

It is increasingly important to monitor sliding interfaces within machines,since this is where both energy is lost,and failures *** emission(AE)techniques offer a way to monitor contacts remotely without requiring transparent or electrically conductive ***,acoustic data from sliding contacts is notoriously complex and difficult to ***,we simultaneously measure coefficient of friction(with a conventional force transducer)and acoustic emission(with a piezoelectric sensor and high acquisition rate digitizer)produced by a steel‒steel rubbing *** data is then used to train machine learning(mL)algorithms(e.g.,Gaussian process regression(GPR)and support vector machine(SVm))to correlated acoustic emission with *** training requires the dense AE data to first be reduced in size and a range of processing techniques are assessed for this(e.g.,down-sampling,averaging,fast Fourier transforms(FFTs),histograms).Next,fresh,unseen AE data is given to the trained model and the resulting friction predictions are compared with the directly measured *** is excellent agreement between the measured and predicted friction when the GPR model is used on AE histogram data,with root mean square(RmS)errors as low as 0.03 and Pearson correlation coefficients reaching ***,predictions remain accurate despite changes in test conditions such as normal load,reciprocating frequency,and stroke *** paves the way for remote,acoustic measurements of friction in inaccessible locations within machinery to increase mechanical efficiency and avoid costly failure/needless maintenance.

关键词： acoustic emission condition monitoring friction machine learning Gaussian process regression support vector machine

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A general mirror equivalence theorem for coset vertex operator algebras

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Science China mathematics 2024年第10期67卷 2237-2282页

作者： robert mcRae Yau mathematical Sciences Center Tsinghua University

We prove a general mirror duality theorem for a subalgebra U of a simple conformal vertex algebra A and its commutant V=ComA（U）.Specifically,we assume that ■ as a U■V-module,where the U-modules Uiare simple and distinct and are objects of a semisimple braided ribbon category of Umodules,and the V-modules Viare semisimple and contained in a（not necessarily rigid） braided tensor category of *** also assume U=ComA（V）.Under these conditions,we construct a braid-reversed tensor equivalence τ:uA→vA,where uAis the semisimple category of U-modules with simple objects Ui,i∈I,and vAis the category of V-modules whose objects are finite direct sums of *** particular,the V-modules Viare simple and distinct,and vAis a rigid tensor *** an application,we find a rigid semisimple tensor subcategory of modules for the Virasoro algebra at central charge 13+6p+6p-1,p∈Z≥2, which is braided tensor equivalent to an abelian 3-cocycle twist of the category of finite-dimensional ***,the Virasoro vertex operator algebra at central charge 13+6p+6p-1is the PSL2（C）-fixed-point subalgebra of a simple conformal vertex algebra w（-p）,analogous to the realization of the Virasoro vertex operator algebra at central charge 13-6p-6p-1as the PSL2（C）-fixed-point subalgebra of the triplet algebra W（p）.

关键词： vertex operator algebras coset conformal field theory braid-reversed tensor equivalence Virasoro algebra

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Necrotic enteritis and antibiotic-free production of broiler chickens:Challenges in testing and using alternative products

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Animal Nutrition 2024年第01期16卷 288-298页

作者： robert J.moore School of Science RMIT University

The global trend towards raising broiler chickens without the use of in-feed antibiotics(IFAs) means that there is an ongoing need to develop alternative treatments capable of delivering the benefits that IFAs previously provided. IFAs supported the productivity performance of chickens and played a key role in maintaining their health. Necrotic enteritis(NE) is an important disease of broilers that affects health,productivity, and welfare, and was previously well controlled by IFAs. However, with the reduction in IFA use, NE is resurgent in some countries. Vaccines and various feed additives, including pre-, pro-, and postbiotics, phytobiotics, fatty acids, and phage therapies have been introduced as alternative methods of NE control. While some of these feed additives have specific activity against the NE pathogen, Clostridium perfringens, most have the more general goal of reinforcing gut health. Extensive reviews of the effects of many of these feed additives on gut health have been published recently. Hence, rather than cover previously well reviewed areas of research this review focuses on the challenges and pitfalls in undertaking experimental assessment of alternative NE treatments and translating laboratory research to real world commercial production settings. The review is based on the author's particular experience,reading, thoughts, and analysis of the available information and inevitably presents a particular understanding that is likely to be at odds with others thinking on these issues. It is put forward to stimulate thinking and discussion on the issues covered.

关键词： Necrotic enteritis

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A detailed rock density model of the Hong Kong territories

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Geodesy and Geodynamics 2024年第1期15卷 75-81页

作者： Albertini Nsiah Ababio robert Tenzer Department of Land Surveying and Geo-Informatics Hong Kong Polytechnic UniversityHong KongChina

We used the geological map and published rock density measurements to compile the digital rock density model for the Hong Kong *** then estimated the average density for the whole *** to our result,the rock density values in Hong Kong vary from 2101 to 2681 kg·m^(-3).These density values are typically smaller than the average density of 2670 kg·m^(-3),often adopted to represent the average density of the upper continental crust in physical geodesy and gravimetric geophysics *** finding reflects that the geological configuration in Hong Kong is mainly formed by light volcanic formations and lava flows with overlying sedimentary deposits at many locations,while the percentage of heavier metamorphic rocks is very low(less than 1%).This product will improve the accuracy of a detailed geoid model and orthometric heights.

关键词： Density model Rock types Gravimetric modeling Hong Kong

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Epidemiology of insertional and midportion Achilles tendinopathy in runners:A prospective cohort study

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Journal of Sport and Health Science 2024年第2期13卷 256-263页

作者： Wenbo Chen Kyra L.A.Cloosterman Sita m.A.Bierma-Zeinstra marienke van middelkoop robert-Jan de Vos Department of Orthopaedic Surgery and Sports medicine Erasmus MC University Medical CenterRotterdam 3015GDthe Netherlands Department of General Practice Erasmus MC University Medical CenterRotterdam 3015GDthe Netherlands Department of Sports medicine Huashan HospitalFudan UniversityShanghai 200040China

Background:Achilles tendinopathy(AT)is a common problem among *** is only limited evidence for risk factors for AT,and most studies have not defined the AT *** study has compared the incidence and risk factors between insertional AT and midportion AT,though they are considered *** study aimed to assess incidence and risk factors of AT based on data from a large prospective *** secondary aim was to explore differences in risk factors between insertional and midportion ***:Participants were recruited from among registered runners at registration for running *** were completed at baseline,1 month before the event,1 week before the event,and 1 month after the *** concerning demographics,training load,registered events,and running-related injuries were collected at *** follow-up questionnaires collected information about new injuries.A pain map was used to diagnose midportion and insertional *** primary outcome was the incidence of *** logistic regression analysis was applied to identify risk factors for the ***:We included 3379 participants with a mean follow-up of 20.4 *** incidence of AT was 4.2%.The proportion of insertional AT was 27.7%and of midportion AT was 63.8%;the remaining proportion was a combined type of insertional and midportion *** had a significantly higher incidence(5%,95%confidence interval(95%CI):4.1%-6.0%)than women(2.8%,95%CI:2.0%-3.8%).AT in the past12 months was the most predominant risk factor for new-onset AT(odds ratio(OR)=6.47,95%CI:4.27-9.81).This was similar for both subcategories of AT(insertional:OR=5.45,95%CI:2.51-11.81;midportion:OR=6.96,95%CI:4.24-11.40).Participants registering for an event with a distance of 10/10.55 km were less likely to develop a new-onset AT(OR=0.59,95%CI:0.36-0.97)or midportion AT(OR=0.47,95%CI:0.23-0.93).Higher age had a significant negative association with insertional AT(OR=0.97,95%CI:0.9

关键词： Achilles tendon injury Incidence Risk factor Running-related injury

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Excess dietary Lys reduces feed intake, stimulates jejunal CCK secretion and alters essential and non‑essential blood AA profile in pigs

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Journal of Animal Science and Biotechnology 2024年第3期15卷 1336-1346页

作者： maximiliano muller Elout Van Liefferinge Alan Tilbrook robert van Barneveld Eugeni Roura Centre for Nutrition and Food Sciences Queensland Alliance for Agriculture and Food InnovationThe University of QueenslandBrisbaneQueensland 4072Australia Laboratory of Animal Nutrition and Animal Product Quality(LANUPRO) Department of Animal Sciences and Aquatic EcologyGhent University339000 GhentFlandersBelgium Centre for Animal Science Queensland Alliance for Agriculture and Food Innovation and the School of Veterinary ScienceThe University of QueenslandBrisbaneQueensland 4072Australia SunPork Group BrisbaneQueensland 4009Australia

Background Commercial diets are frequently formulated to meet or exceed nutrient levels including those of lim-iting essential amino acids(AA)covering potential individual variations within the ***,the provision of dietary excess of AA,such as Lys,may lead to reduced appetite and growth in *** mechanisms modulat-ing these responses have not been extensively *** study evaluated the effect of Lys dietary excesses on performance and satiety biomarkers in post weaning *** Twenty-four pigs aged 21 d and weighing 6.81±0.12kg(mean±SEm)were individually housed and offered 1 of 4 dietary treatments for 3weeks:a diet containing a standardized ileal digestible Lys reaching 100%(T0),120%(T1),150%(T2)or 200%(T3)of the NRC(2012)*** the end of the experiment,blood samples from the cephalic vein of the T0 and T3 groups were obtained for AA *** addition,primary intestinal cultures from T0 pigs were used,following their humane killing,to evaluate the effect of Lys on gut hormone secretion and AA sensors gene expression under ex vivo *** Feed intake was linearly reduced(Pmetabotropic glutamate receptor 1 and the solute carrier family 7 member 2(Pmal jejunum tissues incubated with Lys at 20mmol/L when compared to the control(Lys 0mmol/L).Plasma Lys and Glu(Pmpared to T0 *** contrast,plasma levels of His,Val,Thr,Leu(Pm that excess dietary Lys inhibits hunger in ***,the results provide evidence of pre-and post-absorptive mechanisms modulating these *** dietary excesses should be nar-rowed,when possible,to avoid negative effects of

关键词： Amino acid Blood Cholecystokinin Feed intake Lysine Pig Satiety

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NeuroPNm:model reduction of pore network models using neural networks

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Particuology 2024年第3期86卷 239-251页

作者： robert Jendersie Ali mjalled Xiang Lu Lucas Reineking Abdolreza Kharaghani martin monnigmann Christian Lessig Otto-von-Guericke-Universitat magdeburg Universitatsplatz 2Magdeburg39106Germany Ruhr-Universitat-Bochum Universitatstraβe 150Bochum44801Germany

Reacting particle systems play an important role in many industrial applications,for example biomass drying or the manufacturing of *** numerical modeling and simulation of such systems is therefore of great importance for an efficient,reliable,and environmentally sustainable operation of the *** complex thermodynamical,chemical,and flow processes that take place in the particles are a particular challenge in a ***,typically a large number of particles is involved,rendering an explicit treatment of individual ones impossible in a reactor-level *** approach for overcoming this challenge is to compute effective,physical parameters from single-particle,high-resolution *** can be combined with model reduction methods if the dynamical behaviour of particles must be *** network models with their unrivaled resolution have thereby been used successfully as high-resolution models,for instance to obtain the macroscopic diffusion coeffcient of *** parameter identification and model reduction have recently gained new impetus by the dramatic progress made in machine learning in the last *** report results on the use of neural networks for parameter identification and model reduction based on three-dimensional pore network models(PNm).We believe that our results provide a powerful complement to existing methodologies for reactor-level simulations with many thermally-thick particles.

关键词： Porenetwork models Neural networks Parameter estimation Reduced order model

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The concept of gene therapy for glaucoma:the dream that has not come true yet

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Neural Regeneration Research 2024年第1期19卷 92-99页

作者： robert Sulak Xiaonan Liu Adrian Smedowski Department of Physiology Faculty of Medical Sciences in KatowiceMedical University of Silesia in KatowiceKatowicePoland Institute of Biotechnology HiLIFEUniversity of HelsinkiHelsinkiFinland GlaucoTech Co. KatowicePoland

Gene therapies,despite of being a relatively new therapeutic approach,have a potential to become an important alternative to current treatment strategies in *** glaucoma is not considered a single gene disease,the identified goals of gene therapy would be rather to provide neuroprotection of retinal ganglion cells,especially,in intraocular-pressure-independent *** most commonly reported type of vector for gene delivery in glaucoma studies is adeno-associated virus serotype 2 that has a high tro pism to retinal ganglion cells,res ulting in long-term expression and low immunogenic *** gene thera py studies recruit inducible and genetic animal models of optic neuropathy,like DBA/2J mice model of high-tension glaucoma and the optic nerve *** gene therapy-based neuroprotection of retinal ganglion cells is targeting specific genes translating to growth factors(i.e.,brain derived neurotrophic factor,and its receptor TrkB),regulation of apoptosis and neurodegeneration(i.e.,Bcl-xl,Xiap,FAS system,nicotinamide mononucleotide adenylyl transferase 2,Digit3 and Sarm1),immunomodulation(i.e.,Crry,C3 complement),modulation of neuroinflammation(i.e.,e rythropoietin),reduction of excitotoxicity(i.e.,Com KIlα)and transcription regulation(i.e.,max,Nrf2).On the other hand,some of gene therapy studies focus on lowering intra ocular pressure,by impacting genes involved in both,decreasing aqueous humor production(i.e.,aquaporin 1),and increasing outflow facility(i.e.,COX2,prostaglandin F2a receptor,RhoA/RhoA kinase signaling pathway,mmP1,myocilin).The goal of this review is to summarize the current stateof-art and the direction of development of gene therapy strategies for glaucomatous neuropathy.

关键词： adeno-associated virus gene editing gene therapy glaucoma IOP lowering IOP-independent mechanisms neuroprotection optic nerve optic neuropathy retinal ganglion cells

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Assessment of portable FTIR and Raman spectroscopy for the detection of 2,3-dimethyl-2,3-dinitrobutane(DmDNB)in plastic explosives

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Defence Technology（防务技术） 2024年第4期34卷 11-18页

作者： Jacky Cailes robert Dunsmore Kathryn L.Linge ChemCentre PO Box 1250PerthAustralia

The marplex Convention was established to prevent the manufacture of unmarked plastic explosives and stipulates that a volatile detection agent must be added at the time of ***,to-date,laboratory testing remains the internationally accepted practice for identifying and quantifying the taggants stipulated in the *** this project,portable FTIR and Raman instruments were tested for their ability to detect 2,3-dimethyl-2,3-dinitrobutane(DmDNB),the chemical marker incorporated in plastic explosives that are manufactured within *** both FTIR and Raman instruments detected solid DmDNB(98%purity),field analysis of plastic explosives at an Australian Defence establishment showed that both FTIR and Raman spectra were matched the relevant explosive(RDX or PETN),rather than the DmDNB *** all three plastic explosives tested,the concentration of DmDNB was measured by SPmE-GC-mS to be between 1.8 and 2%,greater than the minimum 1%concentration stipulated by the marplex *** testing with a plastic explosive analogue confirmed that the minor absorption peaks that would characterize low concentrations of DmDNB were masked by absorption bands from other compounds within the ***,while both FTIR and Raman spectroscopy are suitable for detection of plastic explosives,neither rely on the presence of DmDNB for *** is likely that similar results would be found for other taggants stipulated by the marplex Convention,given they are also present in concentrations less than 1%.

关键词： Explosive ICAO taggants 2,3-Dimethyl-2,3-dinitrobutane(DmDNB) Fourier transform infrared(FTIR) Raman

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