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Engineered neuronal microtissue provides exogenous axons for delayed nerve fusion and rapid neuromuscular recovery in rats

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Bioactive Materials 2022年第12期7卷 339-353页

作者： Justin C.Burrell Suradip Das Franco A.Laimo Kritika S.Katiyar Kevin D.Browne Robert B.Shultz Vishal J.tien Phuong t.Vu Dmitriy Petrov Zarina SAli joseph M.Rosen D.Kacy Cullen Center for Brain Injury&Repair Department of NeurosurgeryPerelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPAUSA Department of Bioengineering School of Engineering&Applied ScienceUniversity of PennsylvaniaPhiladelphiaPAUSA Center for Neurotrauma Neurodegeneration&RestorationCorporal Michael J.Crescenz Veterans Affairs Medical CenterPhiladelphiaPA19104USA Axonova Medical LLCPhiladelphiaPAUSA Dartmouth-Hitchcock Medical Center Division of Plastic SurgeryDartmouth CollegeLebanonNHUSA

Nerve injury requiring surgical repair often results in poor functional recovery due to the inability of host axons to re-grow long distances and reform meaningful connections with the target muscle. While surgeons can re-route local axon fascicles to the target muscle, there are no technologies to provide an exogenous source of axons without sacrificing healthy nerves. Accordingly, we have developed tissue engineered neuromuscular interfaces (tE-NMIs) as the first injectable microtissue containing motor and sensory neurons in an anatomically-inspired architecture. tE-NMIs provide axon tracts that are intended to integrate with denervated distal structures and preserve regenerative capacity during prolonged periods without host innervation. Following implant, we found that tE-NMI axons promoted Schwann cell maintenance, integrated with distal muscle, and preserved an evoked muscle response out to 20-weeks post nerve transection in absence of innervation from host axons. By repopulating the distal sheath with exogenous axons, tE-NMIs also enabled putative delayed fusion with proximal host axons, a phenomenon previously not achievable in delayed repair scenarios due to distal axon degeneration. Here, we found immediate electrophysiological recovery after fusion with proximal host axons and improved axon maturation and muscle reinnervation at 24-weeks post-transection (4-weeks following delayed nerve fusion). these findings show that tE-NMIs provide the potential to improve functional recovery following delayed nerve repair.

关键词： Nerve regeneration Neuromuscular injury Muscle preservation tissue engineering Microtissue Axon fusion

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tCR-pMHC: may the force be of you?

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Cellular & Molecular Immunology 2021年第7期18卷 1622-1623页

作者： joseph S.Murray Xenolaüs Genetics LLC Los AngelesCA90024USA

theα/βcomponent of the t-cell antigen receptor(tCR)is a transmembrane heterodimer containing genetically variable(V)domains and constant domains within each polypeptide chain.1 the Vαand Vβdomains bind with a clonally unique(clonotypic)interface angle,2 and the complementary determining regions(CDR1,CDR2,and CDR3)manifest as‘loops’between anti-parallelβ-strands of the overall sandwich ofβ-sheets with a central disulfide *** with immunoglobulins,the CDR1 and CDR2 loops are encoded in the germline via the particular V-region DNA segment involved in the RAG1/RAG2 recombination mechanism responsible for somatic construction,together with the D-and/or J-segment,of the third loop,CDR3.1,3 As shown by multiple solved X-ray crystallography structures,the CDRs contain the closest amino acid(a.a.)contacts with the peptide(p)plus the major histocompatibility complex(MHC)protein(together abbrev.,pMHC)composite *** rigorous selection in the thymus for only those tCRs that should function properly in the particular individual after birth(MHC restriction),4 t cells function clonally as well,i.e.,different t-cell clones display differential responses to not only different pMHC ligands but also perhaps more importantly,to the same pMHC ligands.5,6 A long-standing question is how(not whether)tCR V-domain binding to pMHC is ultimately responsible for such vast biological outcomes as protection *** to infectious diseases,atopy,the onset of autoimmune diseases,and the success of various types of transplantation.

关键词： properly sandwich rigorous

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New Azulene-type Sesquiterpenoids from the Fruiting Bodies of Lactarius deliciosus

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Natural Products and Bioprospecting 2017年第3期7卷 269-273页

作者： Michel Feussi tala Jianchun Qin joseph t.Ndongo Hartmut Laatsch Institute of Organic and Biomolecular Chemistry University of GoettingenTammannstrasse 237077 GottingenGermany School of Plant Science Jilin UniversityXian Road No.5333Changchun 130062JilinPeople’s Republic of China

In the^(1)H NMR-guided fractionation of extracts from the edible mushroom Lactarius deliciosus,two new azulene-type sesquiterpenoids,7-isopropenyl-4-methyl-azulene-1-carboxylic acid(1)and 15-hydroxy-3,6-dihydrolactarazulene(2),together with seven known compounds were *** structures were determined on basis of spectroscopic evidence,as well as by comparing with literature *** the known metabolites,the^(13)C NMR assignment of 15-hydroxy-6,7-dihydrolactarazulene(3)is reported here for the first ***,7-acetyl-4-methylazulene-1-carbaldehyde(5)displayed a moderate antibacterial activity against Staphylococcus aureus.

关键词： Lactarius deliciosus Fungal pigments Azulene sesquiterpenoids Antibacterial activity

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Simulation of Desert-Scrub Growth: A Forcing to Warmer and More Pluvial Climate

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Advances in Atmospheric Sciences 1992年第4期9卷 441-450页

作者： joseph Otterman tel Aviv University Ramat Aviv Israel present address NASA/Goddard Space Flight Center Code 911 Greenbelt MD 20771 U. S. A.esert-fringe vegetation growing over bright sandy soils reduces the surface albedo from above 0.4 to well below 0.3. Called desert-scrub these shrubs form a predominantly vertical clumps protruding from the soil-level thereby significantly increasing the coefficient of turbulent heat transfer from the surface. The impact on global and desert-belt climate of changes in these two surface characteristics was simulated by a multi-layer energy balance tnodel. Evaluated only as a forcing to a further climatic change (that is without accounting for any possible feedbacks) the results are: if vegetation (such as apparently existed under the warmer climate of 6000 BP ) grows over large areas in the arid currently bare-soil regions the annual Northern Hemisphere surface temperature increases by 0.7t (by 0.6'C in July ) the surface temperature over land in the 20-30°N zone increases by 0.9℃ in both the annual and the July means and the land-ocean annual temperature contrast in this zone increases by 0.25℃(0.2° in July). These results represent the combined influence of the reduction in the surface albedo and of the increase in the coefficient of turbulent heat transfer. In the desert-belt zones the increase in the transfer coefficient sharply reduces the land temperature and the land-ocean temperature contrast from the values produced by the albedo change alone. This reduction must be attributed to the increased land-to-ocean circulation (which our model does not evaluate explicitly). Considering that a stronger circulation (resulting from land-ocean temperature contrast) generally forces a higher rainfall the vegetation which emerged in the arid regions during the post-glacial optimum should be considered a significant positive feedback towards a still warmer and also a more pluvial climate. Our study may have implications for the 21st century if the global warming expected from the

Desert-fringe vegetation growing over bright, sandy soils reduces the surface albedo from above 0.4 to well below 0.3. Called desert-scrub, these shrubs form a predominantly vertical clumps protruding from the soil-level, thereby significantly increasing the coefficient of turbulent heat transfer from the surface. the impact on global and desert-belt climate of changes in these two surface characteristics was simulated by a multi-layer energy balance tnodel. Evaluated only as a forcing to a further climatic change (that is, without accounting for any possible feedbacks) the results are: if vegetation (such as apparently existed under the warmer climate of 6,000 BP ) grows over large areas in the arid, currently bare-soil regions, the annual Northern Hemisphere surface temperature increases by 0.7t (by 0.6'C in July ), the surface temperature over land in the 20-30°N zone increases by 0.9℃ in both the annual and the July means, and the land-ocean annual temperature contrast in this zone increases by 0.25℃(0.2° in July). these results represent the combined influence of the reduction in the surface albedo and of the increase in the coefficient of turbulent heat transfer. In the desert-belt zones, the increase in the transfer coefficient sharply reduces the land temperature and the land-ocean temperature contrast from the values produced by the albedo change alone. this reduction must be attributed to the increased land-to-ocean circulation (which our model does not evaluate explicitly). Considering that a stronger circulation (resulting from land-ocean temperature contrast) generally forces a higher rainfall, the vegetation which emerged in the arid regions during the post-glacial optimum should be considered a significant positive feedback towards a still warmer, and also a more pluvial, climate. Our study may have implications for the 21st century, if the global warming expected from the enhanced greenhouse effects is accompanied by increased precipitation over the

关键词： Simulation of Desert-Scrub Growth A Forcing to Warmer and More Pluvial Climate

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Validity of a noninvasive estimation of deep body temperature when wearing personal protective equipment during exercise and recovery

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Military Medical Research 2019年第4期6卷 328-339页

作者： Andrew P.Hunt Mark J.Buller Matthew J.Maley joseph t.Costello Ian B.Stewart School of Exercise and Nutrition Sciences&Institute of Health and Biomedical Innovation Queensland University of TechnologyBrisbaneQLDAustralia United States Army Research Institute of Environmental Medicine NatickMAUSA Extreme Environments Laboratory Department of Sport and Exercise ScienceUniversity of PortsmouthPortsmouthUK

Background:Deep body temperature is a critical indicator of heat ***,direct measures are often invasive,costly,and difficult to implement in the *** study assessed the agreement between deep body temperature estimated from heart rate and that measured directly during repeated work bouts while wearing explosive ordnance disposal(EOD)protective clothing and during ***:Eight males completed three work and recovery periods across two separate *** consisted of treadmill walking on a 1%incline at 2.5,4.0,or 5.5 km/h,in a random order,wearing EOD protective *** temperature and relative humidity were maintained at 24℃and 50%[Wet bulb globe temperature(WBGt)(20.9±1.2)℃]or 32℃and 60%[WBGt(29.0±0.2)℃]on the separate days,*** rate and gastrointestinal temperature(tGI)were monitored continuously,and deep body temperature was also estimated from heart rate(ECtemp).Results:the overall systematic bias between tGI and ECtemp was 0.01℃with 95%limits of agreement(Lo A)of±0.64℃and a root mean square error of 0.32℃.the average error statistics among participants showed no significant differences in error between the exercise and recovery periods or the environmental *** tGI levels of(37.0–37.5)℃,(37.5–38.0)℃,(38.0–38.5)℃,and>38.5℃,the systematic bias and±95%Lo A were(0.08±0.58)℃,(–0.02±0.69)℃,(–0.07±0.63)℃,and(–0.32±0.56)℃,***:the findings demonstrate acceptable validity of the ECtemp up to 38.5℃.Conducting work within an ECtemp limit of 38.4℃,in conditions similar to the present study,would protect the majority of personnel from an excessive elevation in deep body temperature(>39.0℃).

关键词： Protective clothing Body core temperature Heat strain Heat stress Kalman filter Explosive ordnance disposal

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A simulation study of using active traffic management strategies on congested freeways

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Journal of Modern transportation 2012年第3期20卷 178-184页

作者： Ramakrishna VADDE joseph O. SAI Mohammed A. FARUQI Pat t. LEELANI texas A&M University-Kingsville Department of Civil Engineering MSC 194Kingsville Texas 78363 USA

the main objective of this study is to evaluate the effectiveness of using active traffic management （AtM） strategies on freeways in terms of the driver＇s behavior and operational impacts. A few test beds were selected to evaluate the impacts of AtM such as speed harmonization, shoulder utilization, and ramp metering. test beds used in this study were at places where an AtM is either proposed or previously implemented, i.e., where data exists for condi- tions prior to and after the implementation of AtM. Data collected from the test beds were used in a simulation model to evaluate the impacts of each AtM strategy on speed, travel time, and crash rates. Simulation results indicated that the implementation of speed harmonization on US 90 showed a 14% reduction in crashes and a 2%-3% increase in freeway speed; the implementation of hard shoulders on US 90 showed a 39% increase in travel time, 22% increase in freeway capacity and 60% decrease in delays; and the implementation of ramp metering on US 59 between Bissonnet St. and Fondern road showed a decrease of 23 % in freeway travel time, a 14% increase in freeway speed and 11% decrease in accident rates.

关键词： active traffic management VISSIM speed harmonization hard shoulder ramp metering

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A systematic review of pre-hospital shoulder reduction techniques for anterior shoulder dislocation and the effect on patient return to function

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Chinese Journal of traumatology 2020年第5期23卷 295-301页

作者： joseph t.Fennelly Lysander Gourbault Gregory Neal-Smith Akhilesh Pradhan Venkat Gade Jonathan A.Baxter trauma and Orthopaedics Stoke Mandeville HospitalAylesburyHP218ALUK trauma and Orthopaedics Royal United HospitalBathBA13NGUK

Purpose:the majority of acute anterior shoulder dislocations are sustained during sports and wilderness *** management of acute dislocations in the pre-hospital setting is currently without guidelines based on the *** study aims to assess the risk of acute complications in pre-hospital shoulder reduction and identify which pre-hospital reduction technique has the highest success rate in the published ***:the involved databases were Allied and Complementary Medicine,CENtRAL,CINAHL,Cochrane Database of Systematic Reviews,Embase,Europe PMC,Ovid MEDLINE®,Pedro,Proquest,trip,and World Health Organization International Clinical trials Registry *** original research of high methodological quality was included,which was defined by the recently developed assessment tooleassessing the methodological quality of published papers(AMQPP)and investigated the management of acute anterior shoulder dislocations in the pre-hospital ***:two hundred and ninety-eight articles were identified and screened.A full text review was performed on 40 *** articles published between 2015 and 2018 met the inclusion criteria.A total of 181 patients were included with the study duration ranging from 6 to 60 *** studies reported zero immediate complication following pre-hospital reduction and there were no documented subsequent adverse events regardless of the technique *** resolution of neurological symptoms was observed following the early and successful pre-hospital *** attempt success rate,when performed by skilled practitioners,ranged from 72.3%to 94.9%.Conclusion:Pre-hospital shoulder reduction appears to be a safe and feasible option when carried out with the appropriate expertise.A novel reduction technique adapted from the mountain medicine diploma course at the University of Paris North was found to have the highest first attempt reduction success rate of 94.9%.Other techniques described in the lite

关键词： Should dislocation Pre-hospital reduction Success rate Imaging

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Acoustofluidic separation enables early diagnosis of traumatic brain injury based on circulating exosomes

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Microsystems & Nanoengineering 2021年第2期7卷 59-69页

作者： Zeyu Wang Haichen Wang Ryan Becker joseph Rufo Shujie Yang Brian E.Mace Mengxi Wu Jun Zou Daniel t.Laskowitz tony Jun Huang Department of Mechanical Engineering and Materials Science Duke UniversityDurhamNC27708USA Department of Neurology Duke UniversityDurhamNC27708USA Department of Biomedical Engineering Duke UniversityDurhamNC27708USA Department of Geriatrics Duke UniversityDurhamNC27708USA Department of Electrical&Computer Engineering Texas A&M UniversityCollege StationTX77840USA

traumatic brain injury(tBI)is a global cause of morbidity and *** management and risk stratification of patients with tBI is made difficult by the relative insensitivity of screening radiographic studies as well as by the absence of a widely available,noninvasive diagnostic *** particular,a blood-based biomarker assay could provide a quick and minimally invasive process to stratify risk and guide early management strategies in patients with mild tBI(mtBI).Analysis of circulating exosomes allows the potential for rapid and specific identification of tissue *** applying acoustofluidic exosome separation—which uses a combination of microfluidics and acoustics to separate bioparticles based on differences in size and acoustic properties—we successfully isolated exosomes from plasma samples obtained from mice after *** isolation eliminated interference from other blood components,making it possible to detect exosomal biomarkers for tBI via flow *** cytometry analysis indicated that exosomal biomarkers for tBI increase in the first 24 h following head trauma,indicating the potential of using circulating exosomes for the rapid diagnosis of *** levels of tBI biomarkers were only detected in the samples separated via acoustofluidics;no changes were observed in the analysis of the raw plasma *** finding demonstrated the necessity of sample purification prior to exosomal biomarker *** acoustofluidic exosome separation can easily be integrated with downstream analysis methods,it shows great potential for improving early diagnosis and treatment decisions associated with tBI.

关键词： diagnosis separation injury

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Immunotherapy in colorectal cancer: Available clinical evidence,challenges and novel approaches

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World Journal of Gastroenterology 2019年第29期25卷 3920-3928页

作者： joseph tintelnot Alexander Stein Department of Internal Medicine II (Oncology Center) University Medical Center Hamburg-Eppendorf Hamburg 20246 Germany

In contrast to other tumor types, immunotherapy has not yet become a relevant part of the treatment landscape of unselected colorectal cancer. Beside the small subgroup of deficient mismatch repair or microsatellite instable tumors (about 5%) as a surrogate for high mutational burden and subsequently high neoantigen load and immunogenicity, inhibitors of programmed death 1 (PD-1), programmed death ligand 1 (PD-L1) and/or cytotoxic t lymphocyte-associated antigen-4 were not or only modestly effective in metastatic colorectal cancer. thus, a variety of combination approaches with chemotherapy, targeted therapy, toll-like receptor agonists, local ablation or oncolytic viruses is currently being evaluated in different disease settings. Despite several encouraging single arm data already presented or published, available randomized data are unimpressive. Adding PD-1/PD-L1 inhibitors to fluoropyrimidines and bevacizumab maintenance showed no beneficial impact on delaying progression. In refractory disease, the combination of PD-1/PD-L1 and MEK inhibitor was not different from regorafenib, whereas a PD-1/PD-L1 and cytotoxic t lymphocyteassociated antigen-4 inhibitor combination demonstrated better overall survival compared to supportive care alone. Clinical trials in all disease settings applying different combination approaches are ongoing and may define the role of immunotherapy in colorectal cancer.

关键词： Immunotherapy Combination Colorectal cancer Metastatic Adjuvant

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Systematic Biological Upgrade of a Urea Fertilizer Effluent treatment Plant Using GPS

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Open Journal of Applied Sciences 2023年第8期13卷 1457-1477页

作者： Isyaku Ahmad joseph t. Akintola Regina J. Patinvoh Wilson F. Ekpotu Martins C. Obialor Philemon Chukwuebuka Udom Process (Urea) Department Dangote Fertiliser Limited Lagos Nigeria Department of Research & Development Vitapur Nigeria Limited Lagos Nigeria Department of Chemical Engineering Faculty of Engineering Lagos State University Lagos Nigeria Department of Chemical & Petroleum Engineering University of Uyo Akwa Ibom Nigeria Department of Chemical Engineering Federal University of Owerri Owerri Nigeria

the use of modeling and simulation has developed into a critical tool for the sustainable management of wastewater, especially when it comes to replicating the complex biochemical procedures required for fertilizer effluent treatment, which calls for a significant amount of wastewater-related data. the biological improvement of a urea fertilizer effluent via GPS* simulation was carried out in this work using a methodical process. Using established analytical techniques, temperature, total suspended solids (tSS), biochemical oxygen demand (BOD), total phosphorus (t/), chemical oxygen demand (COD), total nitrogen (tN), total nitrate (NO3), electric conductivity (EC), turbidity, residual chlorine, urea, NH3, and heavy metals (Cu, Cd, Cr, Pb, Ni, and Fe) were assessed. the research revealed that the measured values from the fertilizer factory outfall effluent had high concentrations of all the physicochemical water quality indicators, with the exception of tSS, PO4-, SO4-, and NO3-. these concentrations are higher compared to the authorized limits or suggested values by the Federal Environmental Protection Agency (FEPA). to improve the therapy biologically, however, a modeling and simulation program (GPS-X, version 8.0) was used with the physicochemical information gathered from the studied sample. the results of the treated water simulation showed that the concentrations of BOD5 and COD had been significantly reduced by 35% and 44%, respectively. Additionally, it was discovered that total phosphorus (tP), nitrate (N), and total nitrogen (tN) were all within the permitted FEPA limit. the results revealed good treatment performance of the wastewater with increasing concentration of acetic acid and sodium hydroxide. Hence, the results of this research work identify the need for proper treatment of fertilizer industry effluents prior to their release into the environment.

关键词： Fertilizer Wastewater Effluent Discharge Basin Outfall Basin Physiochemical Analysis GPS* Modelling & Simulation

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