Worldwide trends in mobile electrification,largely driven by the popularity of electric vehicles(EVs)will skyrocket demands for lithium-ion battery(LIB)production.As such,up to four million metric tons of LIB waste fr...Worldwide trends in mobile electrification,largely driven by the popularity of electric vehicles(EVs)will skyrocket demands for lithium-ion battery(LIB)production.As such,up to four million metric tons of LIB waste from EV battery packs could be generated from 2015 to 2040.LIB recycling directly addresses concerns over longterm economic strains due to the uneven geographic distribution of resources(especially for Co and Li)and environmental issues associated with both landfilling and raw material extraction.However,LIB recycling infrastructure has not been widely adopted,and current facilities are mostly focused on Co recovery for economic gains.This incentive will decline due to shifting market trends from LiCoO2 toward cobalt-deficient and mixed-metal cathodes(eg,LiNi1/3Mn1/3Co1/3O2).Thus,this review covers recycling strategies to recover metals in mixed-metal LIB cathodes and comingled scrap comprising different chemistries.As such,hydrometallurgical processes can meet this criterion,while also requiring a low environmental footprint and energy consumption compared to pyrometallurgy.Following pretreatment to separate the cathode from other battery components,the active material is dissolved entirely by reductive acid leaching.A complex leachate is generated,comprising cathode metals(Li+,Ni2+,Mn2+,and Co2+)and impurities(Fe3+,Al3+,and Cu2+)from the current collectors and battery casing,which can be separated and purified using a series of selective precipitation and/or solvent extraction steps.Alternatively,the cathode can be resynthesized directly from the leachate.展开更多
The diagnostic approach to a possible pancreatic mass lesion relies first upon various non-invasive imaging modalities, including computed tomography, ultrasound, and magnetic resonance imaging techniques. Once a susp...The diagnostic approach to a possible pancreatic mass lesion relies first upon various non-invasive imaging modalities, including computed tomography, ultrasound, and magnetic resonance imaging techniques. Once a suspect lesion has been identified, tissue acquisition for characterization of the lesion is often paramount in developing an individualized therapeutic approach. Given the high prevalence and mortality associated with pancreatic cancer, an ideal approach to diagnosing pancreatic mass lesions would be safe, highly sensitive, and reproducible across various practice settings. Tools, in addition to radiologic imaging, currently employed in the initial evaluation of a patient with a pancreatic mass lesion include serum tumor markers, endoscopic retrograde cholangiopancreatography, and endoscopic ultrasound-guided fine needle aspiration(EUS-FNA). EUS-FNA has grown to become the gold standard in tissue diagnosis of pancreatic lesions.展开更多
Ependymomas are a somewhat diverse category of glial tumors that often develop from the lining of the brain’s ventricles, or the spinal cord’s central canal. They make up 5% of all neuroepithelial tumors, 10% of pae...Ependymomas are a somewhat diverse category of glial tumors that often develop from the lining of the brain’s ventricles, or the spinal cord’s central canal. They make up 5% of all neuroepithelial tumors, 10% of paediatric brain tumors, and up to 33% of brain tumors in children under the age of three. Hydrocephalus is one of the complications, and it can be identified as progressive macrocephaly or increasing head circumference crossing percentiles, nausea, vomiting, poor appetite, irritability, and regression of developmental milestones.展开更多
Magnesium(Mg)–based alloys are becoming attractive materials for medical applications as temporary bone implants for support of fracture healing,e.g.as a suture anchor.Due to their mechanical properties and biocompat...Magnesium(Mg)–based alloys are becoming attractive materials for medical applications as temporary bone implants for support of fracture healing,e.g.as a suture anchor.Due to their mechanical properties and biocompatibility,they may replace titanium or stainless-steel implants,commonly used in orthopedic field.Nevertheless,patient safety has to be assured by finding a long-term balance between metal degradation,osseointegration,bone ultrastructure adaptation and element distribution in organs.In order to determine the implant behavior and its influence on bone and tissues,we investigated two Mg alloys with gadolinium contents of 5 and 10 wt percent in comparison to permanent materials titanium and polyether ether ketone.The implants were present in rat tibia for 10,20 and 32 weeks before sacrifice of the animal.Synchrotron radiation-based micro computed tomography enables the distinction of features like residual metal,degradation layer and bone structure.Additionally,X-ray diffraction and X-ray fluorescence yield information on parameters describing the bone ultrastructure and elemental composition at the bone-to-implant interface.Finally,with element specific mass spectrometry,the elements and their accumulation in the main organs and tissues are traced.The results show that Mg-xGd implants degrade in vivo under the formation of a stable degradation layer with bone remodeling similar to that of Ti after 10 weeks.No accumulation of Mg and Gd was observed in selected organs,except for the interfacial bone after 8 months of healing.Thus,we confirm that Mg-5Gd and Mg-10Gd are suitable material choices for bone implants.展开更多
Adoptive cell therapy(ACT)is an immunotherapy strategy for cancer that has seen widespread clinical success.During ACT,patient-derived lymphocytes are stimulated with the antigen of interest ex vivo,proliferated,then ...Adoptive cell therapy(ACT)is an immunotherapy strategy for cancer that has seen widespread clinical success.During ACT,patient-derived lymphocytes are stimulated with the antigen of interest ex vivo,proliferated,then returned to the patient to initiate an antigen-specific antitumor response.While effective,this process is resource-intensive and logistically impossible for many patients.Particulate artificial antigen presenting cells(aAPCs)offer a potential“off-the-shelf”alternative to ex vivo ACT.While particulate aAPCs perform well in vitro,they have had limited success in vivo due to poor bioavailability after injection.Barriers to bioavailability include rapid clearance,unfavorable biodistribution,and inadequate interactions with CD8+T cells at sites of interest.Biomaterial properties such as elasticity have been shown to vastly impact the bioavailability and particle-cell interactions,but this has yet to be investigated in the context of aAPCs for in vivo T-cell stimulation.Previous literature likewise indicates that biomaterial properties,especially elasticity,can modulate T-cell activation in vitro.With the goal of creating a more biomimetic,next-generation particulate aAPC,we developed a poly(ethylene)glycol hydrogel particle platform with tunable elasticity to investigate the impact of elasticity on antigen-specific T cell activation for in vivo adoptive transfer.Using this knowledge,we were able to gain more precise control over in vivo T cell activation and investigate possible mechanisms including the effects of aAPC elasticity on T cell binding,macrophage uptake,and the protein corona.展开更多
BACKGROUND Major depressive disorder(MDD)is a highly disabling psychiatric syndrome associated with deficits of specific subpopulations of cortical GABAergic interneurons;however,the underlying molecular mechanism rem...BACKGROUND Major depressive disorder(MDD)is a highly disabling psychiatric syndrome associated with deficits of specific subpopulations of cortical GABAergic interneurons;however,the underlying molecular mechanism remains unknown.Type 3 adenylyl cyclase(ADCY3,AC3),which is important for neuronal excitability,has been implicated in MDD in a genome-wide association study in humans.Moreover,a study reported that ablation of AC3 in mice caused similar symptoms as MDD patients.AIM To determine if disruption of the AC3 gene in different subtypes of GABAergic interneurons of mice causes depression-like behaviors.METHODS Using immunohistochemistry,we investigated the expression of AC3 in two major subtypes GABAergic interneurons:Somatostatin-positive(SST+)and parvalbumin-positive(PV+)neurons.Genetic manipulations were used to selectively disrupt AC3 expression in SST+or PV+interneurons.A series of behavior tests including rotarod test,open field test(OFT),elevated plus maze test(EPM),forced swimming test(FST),and tail suspension test(TST)were used to evaluate the motor ability,anxiety-and depression-like behaviors,respectively.RESULTS Our results indicate that approximately 90.41%of SST+and 91.22%of PV+interneurons express AC3.After ablation of AC3 in SST+interneurons,the mice spent comparable time in the center area in OFT,but significantly less time in the open arms and low frequency of entries to the open arms in EPM.Furthermore,these mice showed prolonged immobility in FST and more freezing in TST.However,there were no significant changes in these behaviors after specific disruption of AC3 in PV+interneurons.CONCLUSION This study indicates that ablation of AC3 in SST+interneurons of mice increases anxiety-and depression-like behaviors in mice,supporting the general hypothesis that decreased AC3 activity may play a role in human depression.展开更多
BACKGROUND Endoscopic ultrasound(EUS)-guided main pancreatic duct(PD)access may be used when conventional endoscopic retrograde cholangiopancreatography(ERCP)techniques fail.The use of a percutaneous transluminal angi...BACKGROUND Endoscopic ultrasound(EUS)-guided main pancreatic duct(PD)access may be used when conventional endoscopic retrograde cholangiopancreatography(ERCP)techniques fail.The use of a percutaneous transluminal angioplasty balloon(PTAB),originally developed for vascular interventions,can be used to facilitate transmural(e.g.,transgastric)PD access and to dilate high-grade pancreatic strictures.AIM To describe the technique,efficacy,and safety of PTABs for EUS-guided PD interventions.METHODS Patients who underwent EUS with use of a PTAB from March 2011 to August 2021 were retrospectively identified from a tertiary care medical center supply database.PTABs included 3-4 French angioplasty catheters with 3-4 mm balloons designed to use over a 0.018-inch guidewire.The primary outcome was technical success.Secondary outcomes included incidence of adverse events(AEs)and need for early reintervention.RESULTS A total of 23 patients were identified(48%female,mean age 55.8 years).Chronic pancreatitis was the underlying etiology in 13(56.5%)patients,surgically altered anatomy(SAA)with stricture in 7(30.4%),and SAA with post-operative leak in 3(13.0%).Technical success was achieved in 20(87%)cases.Overall AE rate was 26%(n=6).All AEs were mild and included 1 pancreatic duct leak,2 cases of post-procedure pancreatitis,and 3 admissions for post-procedural pain.No patients required early re-intervention.CONCLUSION EUS-guided use of PTABs for PD access and/or stricture management is feasible with an acceptable safety profile and can be considered in patients when conventional ERCP cannulation fails.展开更多
National spatial data infrastructures are key to achieving the Digital Earth vision.In many cases,national datasets are integrated from local datasets created and maintained by municipalities.Examples are address,buil...National spatial data infrastructures are key to achieving the Digital Earth vision.In many cases,national datasets are integrated from local datasets created and maintained by municipalities.Examples are address,building and topographic information.Integration of local datasets may result in a dataset satisfying the needs of users of national datasets,but is it productive for those who create and maintain the data?This article presents a stakeholder analysis of the Basisregistratie Adressen en Gebouwen(BAG),a collection of base information about addresses and buildings in the Netherlands.The information is captured and maintained by municipalities and integrated into a national base register by Kadaster,the Cadastre,Land Registry and Mapping Agency of the Netherlands.The stakeholder analysis identifies organisations involved in the BAG governance framework,describes their interests,rights,ownerships and responsibilities in the BAG,and maps the relationships between them.Analysis results indicate that Kadaster and the municipalities have the highest relative importance in the governance framework of the BAG.The study reveals challenges of setting up a governance framework that maintains the delicate balance between the interests of all stakeholders.The results provide guidance for SDI role players setting up governance frameworks for national or global datasets.展开更多
Magnesium is attractive for the application as a temporary bone implant due to its inherent biodegradability,non-toxicity and suitable mechanical properties.The degradation process of magnesium in physiological enviro...Magnesium is attractive for the application as a temporary bone implant due to its inherent biodegradability,non-toxicity and suitable mechanical properties.The degradation process of magnesium in physiological environments is complex and is thought to be a diffusion-limited transport problem.We use a multi-scale imaging approach using micro computed tomography and transmission X-ray microscopy(TXM)at resolutions below 40 nm.Thus,we are able to evaluate the nanoporosity of the degradation layer and infer its impact on the degradation process of pure magnesium in two physiological solutions.Magnesium samples were degraded in simulated body fluid(SBF)or Dulbecco’s modified Eagle’s medium(DMEM)with 10%fetal bovine serum(FBS)for one to four weeks.TXM reveals the three-dimensional interconnected pore network within the degradation layer for both solutions.The pore network morphology and degradation layer composition are similar for all samples.By contrast,the degradation layer thickness in samples degraded in SBF was significantly higher and more inhomogeneous than in DMEM+10%FBS.Distinct features could be observed within the degradation layer of samples degraded in SBF,suggesting the formation of microgalvanic cells,which are not present in samples degraded in DMEM+10%FBS.The results suggest that the nanoporosity of the degradation layer and the resulting ion diffusion processes therein have a limited influence on the overall degradation process.This indicates that the influence of organic components on the dampening of the degradation rate by the suppression of microgalvanic degradation is much greater in the present study.展开更多
Highly controlled particle-assisted growth of semiconductor nanowires has been performed for many years,and a number of novel nanowire-based devices have been demonstrated.Full control of the epitaxial growth is requi...Highly controlled particle-assisted growth of semiconductor nanowires has been performed for many years,and a number of novel nanowire-based devices have been demonstrated.Full control of the epitaxial growth is required to optimize the performance of devices,and gold seed particles are known to provide the most controlled growth.Successful nanowire growth from gold particles generated and deposited by various different methods has been reported,but no investigation has yet been performed to compare the effects of gold particle generation and deposition methods on nanowire growth.In this article we present a direct comparative study of the effect of the gold particle creation and deposition methods on nanowire growth characteristics and nanowire crystal structure,and investigate the limitations of the different generation and deposition methods used.展开更多
Cross-gap light emission is reported in n-type unipolar GaN/AlN double-barrier heterostructure diodes at room temperature.Three different designs were grown on semi-insulating bulk GaN substrates using molecular beam ...Cross-gap light emission is reported in n-type unipolar GaN/AlN double-barrier heterostructure diodes at room temperature.Three different designs were grown on semi-insulating bulk GaN substrates using molecular beam epitaxy(MBE).All samples displayed a single electroluminescent spectral peak at 360 nm with full-width at half-maximum(FWHM)values no greater than 16 nm and an external quantum efficiency(EQE)of≈0.0074%at 18.8 mA.In contrast to traditional GaN light emitters,p-type doping and p-contacts are completely avoided,and instead,holes are created in the GaN on the emitter side of the tunneling structure by direct interband(that is,Zener)tunneling from the valence band to the conduction band on the collector side.The Zener tunneling is enhanced by the high electric fields(~5×106 V cm^(−1))created by the notably large polarization-induced sheet charge at the interfaces between the AlN and GaN.展开更多
Based on the existing Land Surface Physical Process Models(Deardorff, Dickinson, LIU, Noilhan, Seller, ZHAO), a Comprehensive Land Surface Physical Process Model (CLSPPM) is developed by considering the different phys...Based on the existing Land Surface Physical Process Models(Deardorff, Dickinson, LIU, Noilhan, Seller, ZHAO), a Comprehensive Land Surface Physical Process Model (CLSPPM) is developed by considering the different physical processes of the earth's surface-vegetation-atmosphere system more completely. Compared with SiB and BATS, which are famous for their detailed parameterizations of physical variables, this simplified model is more convenient and saves much more computation time. Though simple, the feas...展开更多
AIM: To determine the feasibility and safety of transgastric direct endoscopic necrosectomy(DEN) in patients with walled-off necrosis(WON) and gastric varices. METHODS: A single center retrospective study of consecuti...AIM: To determine the feasibility and safety of transgastric direct endoscopic necrosectomy(DEN) in patients with walled-off necrosis(WON) and gastric varices. METHODS: A single center retrospective study of consecutive DEN for WON was performed from 2012 to 2015. All DEN cases with gastric fundal varices noted on endoscopy, computed tomography(CT) or magnetic resonance imaging(MRI) during the admission for DEN were collected for analysis. In all cases, external urethral sphincter(EUS) with doppler was used to exclude the presence of intervening gastric varices or other vascular structures prior to 19 gauge fine-needle aspiration(FNA) needle access into the cavity. The tract was serially dilated to 20 mm and was entered with an endoscope for DEN. Pigtail stents were placed to facilitate drainage of the cavity. Procedure details were recorded. Comprehensive chart review was performed to evaluate for complications and WON recurrence. RESULTS: Fifteen patients who underwent DEN for WON had gastric varices at the time of their procedure. All patients had an INR < 1.5 and platelets > 50. Of these patients, 11 had splenic vein thrombosis and 2 had portal vein thrombosis. Two patients had isolated gastric varices, type 1 and the remaining 13 had > 5 mm gastric submucosal varices on imaging by CT, MRI or EUS. No procedures were terminated without completing the DEN for any reason. One patient had self-limited intraprocedural bleeding related to balloon dilation of the tract. Two patients experienced delayed bleeding at 2 and 5 d post-op respectively. One required no therapy or intervention and the other received 1unit transfusion and had an EGD which revealed no active bleeding. Resolution rate of WON was 100%(after up to 2 additional DEN in one patient) and no patients required interventional radiology or surgical interventions. CONCLUSION: In patients with WON and gastric varices, DEN using EUS and doppler guidance may be performed safely. Successful resolution of WON does not appear to be compromised by the presence o展开更多
The pandemic of novel coronavirus disease 2019(COVID-19)is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Diabetes mellitus is a risk factor for developing severe illness and a leading cause of ...The pandemic of novel coronavirus disease 2019(COVID-19)is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Diabetes mellitus is a risk factor for developing severe illness and a leading cause of death in patients with COVID-19.Diabetes can precipitate hyperglycaemic emergencies and cause prolonged hospital admissions.Insulin resistance is thought to cause endothelial dysfunction,alveolar capillary micro-angiopathy and interstitial lung fibrosis through pro-inflammatory pathways.Autopsy studies have also demonstrated the presence of microvascular thrombi in affected sections of lung,which may be associated with diabetes.Chest imaging using x-ray(CXR)and computed tomography(CT)of chest is used to diagnose,assess disease progression and severity in COVID-19.This article reviews current literature regarding chest imaging findings in patients with diabetes affected by COVID-19.A literature search was performed on PubMed.Patients with diabetes infected with SARSCoV-2 are likely to have more severe infective changes on CXR and CT chest imaging.Severity of airspace consolidation on CXR is associated with higher mortality,particularly in the presence of co-morbidities such as ischaemic heart disease.Poorly controlled diabetes is associated with more severe acute lung injury on CT.However,no association has been identified between poorlycontrolled diabetes and the incidence of pulmonary thromboembolism in patients with COVID-19.展开更多
基金The authors gratefully acknowledge the financial support from the Natural Sciences and Engineering Research Council of Canada(NSERC)and the University of Waterloo.This work was financially supported by the 111 Project(no.D17007).Karthikeyan Kaliyappan acknowledges the financial support from Henan Normal University,China for this work.Tyler Or was supported through the NSERC Canada Graduate Scholarships—Master’s Program.
文摘Worldwide trends in mobile electrification,largely driven by the popularity of electric vehicles(EVs)will skyrocket demands for lithium-ion battery(LIB)production.As such,up to four million metric tons of LIB waste from EV battery packs could be generated from 2015 to 2040.LIB recycling directly addresses concerns over longterm economic strains due to the uneven geographic distribution of resources(especially for Co and Li)and environmental issues associated with both landfilling and raw material extraction.However,LIB recycling infrastructure has not been widely adopted,and current facilities are mostly focused on Co recovery for economic gains.This incentive will decline due to shifting market trends from LiCoO2 toward cobalt-deficient and mixed-metal cathodes(eg,LiNi1/3Mn1/3Co1/3O2).Thus,this review covers recycling strategies to recover metals in mixed-metal LIB cathodes and comingled scrap comprising different chemistries.As such,hydrometallurgical processes can meet this criterion,while also requiring a low environmental footprint and energy consumption compared to pyrometallurgy.Following pretreatment to separate the cathode from other battery components,the active material is dissolved entirely by reductive acid leaching.A complex leachate is generated,comprising cathode metals(Li+,Ni2+,Mn2+,and Co2+)and impurities(Fe3+,Al3+,and Cu2+)from the current collectors and battery casing,which can be separated and purified using a series of selective precipitation and/or solvent extraction steps.Alternatively,the cathode can be resynthesized directly from the leachate.
文摘The diagnostic approach to a possible pancreatic mass lesion relies first upon various non-invasive imaging modalities, including computed tomography, ultrasound, and magnetic resonance imaging techniques. Once a suspect lesion has been identified, tissue acquisition for characterization of the lesion is often paramount in developing an individualized therapeutic approach. Given the high prevalence and mortality associated with pancreatic cancer, an ideal approach to diagnosing pancreatic mass lesions would be safe, highly sensitive, and reproducible across various practice settings. Tools, in addition to radiologic imaging, currently employed in the initial evaluation of a patient with a pancreatic mass lesion include serum tumor markers, endoscopic retrograde cholangiopancreatography, and endoscopic ultrasound-guided fine needle aspiration(EUS-FNA). EUS-FNA has grown to become the gold standard in tissue diagnosis of pancreatic lesions.
文摘Ependymomas are a somewhat diverse category of glial tumors that often develop from the lining of the brain’s ventricles, or the spinal cord’s central canal. They make up 5% of all neuroepithelial tumors, 10% of paediatric brain tumors, and up to 33% of brain tumors in children under the age of three. Hydrocephalus is one of the complications, and it can be identified as progressive macrocephaly or increasing head circumference crossing percentiles, nausea, vomiting, poor appetite, irritability, and regression of developmental milestones.
基金This publication is part of a project that has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Sk lodowska-Curie grant,agreement No 811226Röntgen-Angström Cluster in project SynchroLoad(05K16CGA)+5 种基金Swedish Research Council 2015-06109German Bundesministerium für Bildung und Forschung in project MgBone(05K16CGB)We acknowledge DESY(Hamburg,Germany),a member of the Helmholtz Association HGF,for the provision of experimental facilities.Parts of this research were carried out at PETRA IIIThe authors would like to thank Diamond Light Source for beamtime(proposal MG25078)Miguel Gomez Gonzalez and Julia Parker for assistance during the experiment at the I14 beamline and during the data analysisThis research was carried out in collaboration with the Quantitative Bio Element Analysis and Mapping(QBEAM)Center at Michigan State University and The National Research Resource for Quantitative Elemental Mapping for the Life Sciences(QE-Map)under Grant P41 GM135018(as well as Grant S10OD026786)from the National Institute of General Medical Sciences of the National Institutes of Health.
文摘Magnesium(Mg)–based alloys are becoming attractive materials for medical applications as temporary bone implants for support of fracture healing,e.g.as a suture anchor.Due to their mechanical properties and biocompatibility,they may replace titanium or stainless-steel implants,commonly used in orthopedic field.Nevertheless,patient safety has to be assured by finding a long-term balance between metal degradation,osseointegration,bone ultrastructure adaptation and element distribution in organs.In order to determine the implant behavior and its influence on bone and tissues,we investigated two Mg alloys with gadolinium contents of 5 and 10 wt percent in comparison to permanent materials titanium and polyether ether ketone.The implants were present in rat tibia for 10,20 and 32 weeks before sacrifice of the animal.Synchrotron radiation-based micro computed tomography enables the distinction of features like residual metal,degradation layer and bone structure.Additionally,X-ray diffraction and X-ray fluorescence yield information on parameters describing the bone ultrastructure and elemental composition at the bone-to-implant interface.Finally,with element specific mass spectrometry,the elements and their accumulation in the main organs and tissues are traced.The results show that Mg-xGd implants degrade in vivo under the formation of a stable degradation layer with bone remodeling similar to that of Ti after 10 weeks.No accumulation of Mg and Gd was observed in selected organs,except for the interfacial bone after 8 months of healing.Thus,we confirm that Mg-5Gd and Mg-10Gd are suitable material choices for bone implants.
基金the NIH for support of this research(P41EB028239)the National Science Foundation Graduate Research Fellowship(Nos.DGE-1746891(SEW)and DGE-1746891(SRS)).
文摘Adoptive cell therapy(ACT)is an immunotherapy strategy for cancer that has seen widespread clinical success.During ACT,patient-derived lymphocytes are stimulated with the antigen of interest ex vivo,proliferated,then returned to the patient to initiate an antigen-specific antitumor response.While effective,this process is resource-intensive and logistically impossible for many patients.Particulate artificial antigen presenting cells(aAPCs)offer a potential“off-the-shelf”alternative to ex vivo ACT.While particulate aAPCs perform well in vitro,they have had limited success in vivo due to poor bioavailability after injection.Barriers to bioavailability include rapid clearance,unfavorable biodistribution,and inadequate interactions with CD8+T cells at sites of interest.Biomaterial properties such as elasticity have been shown to vastly impact the bioavailability and particle-cell interactions,but this has yet to be investigated in the context of aAPCs for in vivo T-cell stimulation.Previous literature likewise indicates that biomaterial properties,especially elasticity,can modulate T-cell activation in vitro.With the goal of creating a more biomimetic,next-generation particulate aAPC,we developed a poly(ethylene)glycol hydrogel particle platform with tunable elasticity to investigate the impact of elasticity on antigen-specific T cell activation for in vivo adoptive transfer.Using this knowledge,we were able to gain more precise control over in vivo T cell activation and investigate possible mechanisms including the effects of aAPC elasticity on T cell binding,macrophage uptake,and the protein corona.
基金Supported by National Natural Science Foundation of China,No.81771208 and No.81971043。
文摘BACKGROUND Major depressive disorder(MDD)is a highly disabling psychiatric syndrome associated with deficits of specific subpopulations of cortical GABAergic interneurons;however,the underlying molecular mechanism remains unknown.Type 3 adenylyl cyclase(ADCY3,AC3),which is important for neuronal excitability,has been implicated in MDD in a genome-wide association study in humans.Moreover,a study reported that ablation of AC3 in mice caused similar symptoms as MDD patients.AIM To determine if disruption of the AC3 gene in different subtypes of GABAergic interneurons of mice causes depression-like behaviors.METHODS Using immunohistochemistry,we investigated the expression of AC3 in two major subtypes GABAergic interneurons:Somatostatin-positive(SST+)and parvalbumin-positive(PV+)neurons.Genetic manipulations were used to selectively disrupt AC3 expression in SST+or PV+interneurons.A series of behavior tests including rotarod test,open field test(OFT),elevated plus maze test(EPM),forced swimming test(FST),and tail suspension test(TST)were used to evaluate the motor ability,anxiety-and depression-like behaviors,respectively.RESULTS Our results indicate that approximately 90.41%of SST+and 91.22%of PV+interneurons express AC3.After ablation of AC3 in SST+interneurons,the mice spent comparable time in the center area in OFT,but significantly less time in the open arms and low frequency of entries to the open arms in EPM.Furthermore,these mice showed prolonged immobility in FST and more freezing in TST.However,there were no significant changes in these behaviors after specific disruption of AC3 in PV+interneurons.CONCLUSION This study indicates that ablation of AC3 in SST+interneurons of mice increases anxiety-and depression-like behaviors in mice,supporting the general hypothesis that decreased AC3 activity may play a role in human depression.
文摘BACKGROUND Endoscopic ultrasound(EUS)-guided main pancreatic duct(PD)access may be used when conventional endoscopic retrograde cholangiopancreatography(ERCP)techniques fail.The use of a percutaneous transluminal angioplasty balloon(PTAB),originally developed for vascular interventions,can be used to facilitate transmural(e.g.,transgastric)PD access and to dilate high-grade pancreatic strictures.AIM To describe the technique,efficacy,and safety of PTABs for EUS-guided PD interventions.METHODS Patients who underwent EUS with use of a PTAB from March 2011 to August 2021 were retrospectively identified from a tertiary care medical center supply database.PTABs included 3-4 French angioplasty catheters with 3-4 mm balloons designed to use over a 0.018-inch guidewire.The primary outcome was technical success.Secondary outcomes included incidence of adverse events(AEs)and need for early reintervention.RESULTS A total of 23 patients were identified(48%female,mean age 55.8 years).Chronic pancreatitis was the underlying etiology in 13(56.5%)patients,surgically altered anatomy(SAA)with stricture in 7(30.4%),and SAA with post-operative leak in 3(13.0%).Technical success was achieved in 20(87%)cases.Overall AE rate was 26%(n=6).All AEs were mild and included 1 pancreatic duct leak,2 cases of post-procedure pancreatitis,and 3 admissions for post-procedural pain.No patients required early re-intervention.CONCLUSION EUS-guided use of PTABs for PD access and/or stricture management is feasible with an acceptable safety profile and can be considered in patients when conventional ERCP cannulation fails.
基金Jantien Stoter is funded by the H2020 European Research Council(ERC)under the European Union’s Horizon 2020 Research and Innovation Framework Programme[grant agreement No 677312 UMnD].
文摘National spatial data infrastructures are key to achieving the Digital Earth vision.In many cases,national datasets are integrated from local datasets created and maintained by municipalities.Examples are address,building and topographic information.Integration of local datasets may result in a dataset satisfying the needs of users of national datasets,but is it productive for those who create and maintain the data?This article presents a stakeholder analysis of the Basisregistratie Adressen en Gebouwen(BAG),a collection of base information about addresses and buildings in the Netherlands.The information is captured and maintained by municipalities and integrated into a national base register by Kadaster,the Cadastre,Land Registry and Mapping Agency of the Netherlands.The stakeholder analysis identifies organisations involved in the BAG governance framework,describes their interests,rights,ownerships and responsibilities in the BAG,and maps the relationships between them.Analysis results indicate that Kadaster and the municipalities have the highest relative importance in the governance framework of the BAG.The study reveals challenges of setting up a governance framework that maintains the delicate balance between the interests of all stakeholders.The results provide guidance for SDI role players setting up governance frameworks for national or global datasets.
文摘Magnesium is attractive for the application as a temporary bone implant due to its inherent biodegradability,non-toxicity and suitable mechanical properties.The degradation process of magnesium in physiological environments is complex and is thought to be a diffusion-limited transport problem.We use a multi-scale imaging approach using micro computed tomography and transmission X-ray microscopy(TXM)at resolutions below 40 nm.Thus,we are able to evaluate the nanoporosity of the degradation layer and infer its impact on the degradation process of pure magnesium in two physiological solutions.Magnesium samples were degraded in simulated body fluid(SBF)or Dulbecco’s modified Eagle’s medium(DMEM)with 10%fetal bovine serum(FBS)for one to four weeks.TXM reveals the three-dimensional interconnected pore network within the degradation layer for both solutions.The pore network morphology and degradation layer composition are similar for all samples.By contrast,the degradation layer thickness in samples degraded in SBF was significantly higher and more inhomogeneous than in DMEM+10%FBS.Distinct features could be observed within the degradation layer of samples degraded in SBF,suggesting the formation of microgalvanic cells,which are not present in samples degraded in DMEM+10%FBS.The results suggest that the nanoporosity of the degradation layer and the resulting ion diffusion processes therein have a limited influence on the overall degradation process.This indicates that the influence of organic components on the dampening of the degradation rate by the suppression of microgalvanic degradation is much greater in the present study.
基金This work was performed within the Nanometer Structure Consortium at Lund University and supported by the Swedish Research Council(VR),the Swedish Foundation for Strategic Research(SSF),the EU program AMON-RA(No.214814)the Knut and Alice Wallenberg Foundation.
文摘Highly controlled particle-assisted growth of semiconductor nanowires has been performed for many years,and a number of novel nanowire-based devices have been demonstrated.Full control of the epitaxial growth is required to optimize the performance of devices,and gold seed particles are known to provide the most controlled growth.Successful nanowire growth from gold particles generated and deposited by various different methods has been reported,but no investigation has yet been performed to compare the effects of gold particle generation and deposition methods on nanowire growth.In this article we present a direct comparative study of the effect of the gold particle creation and deposition methods on nanowire growth characteristics and nanowire crystal structure,and investigate the limitations of the different generation and deposition methods used.
基金funding from the Office of Naval Research under the‘DATE’MURI program(N00014-11-1-0721,program manager:Paul Maki).
文摘Cross-gap light emission is reported in n-type unipolar GaN/AlN double-barrier heterostructure diodes at room temperature.Three different designs were grown on semi-insulating bulk GaN substrates using molecular beam epitaxy(MBE).All samples displayed a single electroluminescent spectral peak at 360 nm with full-width at half-maximum(FWHM)values no greater than 16 nm and an external quantum efficiency(EQE)of≈0.0074%at 18.8 mA.In contrast to traditional GaN light emitters,p-type doping and p-contacts are completely avoided,and instead,holes are created in the GaN on the emitter side of the tunneling structure by direct interband(that is,Zener)tunneling from the valence band to the conduction band on the collector side.The Zener tunneling is enhanced by the high electric fields(~5×106 V cm^(−1))created by the notably large polarization-induced sheet charge at the interfaces between the AlN and GaN.
基金National Natural Science Foundation of China (No. 40275004)State Key Laboratory of Atmosphere Physics and Chemistry
文摘Based on the existing Land Surface Physical Process Models(Deardorff, Dickinson, LIU, Noilhan, Seller, ZHAO), a Comprehensive Land Surface Physical Process Model (CLSPPM) is developed by considering the different physical processes of the earth's surface-vegetation-atmosphere system more completely. Compared with SiB and BATS, which are famous for their detailed parameterizations of physical variables, this simplified model is more convenient and saves much more computation time. Though simple, the feas...
文摘AIM: To determine the feasibility and safety of transgastric direct endoscopic necrosectomy(DEN) in patients with walled-off necrosis(WON) and gastric varices. METHODS: A single center retrospective study of consecutive DEN for WON was performed from 2012 to 2015. All DEN cases with gastric fundal varices noted on endoscopy, computed tomography(CT) or magnetic resonance imaging(MRI) during the admission for DEN were collected for analysis. In all cases, external urethral sphincter(EUS) with doppler was used to exclude the presence of intervening gastric varices or other vascular structures prior to 19 gauge fine-needle aspiration(FNA) needle access into the cavity. The tract was serially dilated to 20 mm and was entered with an endoscope for DEN. Pigtail stents were placed to facilitate drainage of the cavity. Procedure details were recorded. Comprehensive chart review was performed to evaluate for complications and WON recurrence. RESULTS: Fifteen patients who underwent DEN for WON had gastric varices at the time of their procedure. All patients had an INR < 1.5 and platelets > 50. Of these patients, 11 had splenic vein thrombosis and 2 had portal vein thrombosis. Two patients had isolated gastric varices, type 1 and the remaining 13 had > 5 mm gastric submucosal varices on imaging by CT, MRI or EUS. No procedures were terminated without completing the DEN for any reason. One patient had self-limited intraprocedural bleeding related to balloon dilation of the tract. Two patients experienced delayed bleeding at 2 and 5 d post-op respectively. One required no therapy or intervention and the other received 1unit transfusion and had an EGD which revealed no active bleeding. Resolution rate of WON was 100%(after up to 2 additional DEN in one patient) and no patients required interventional radiology or surgical interventions. CONCLUSION: In patients with WON and gastric varices, DEN using EUS and doppler guidance may be performed safely. Successful resolution of WON does not appear to be compromised by the presence o
文摘The pandemic of novel coronavirus disease 2019(COVID-19)is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Diabetes mellitus is a risk factor for developing severe illness and a leading cause of death in patients with COVID-19.Diabetes can precipitate hyperglycaemic emergencies and cause prolonged hospital admissions.Insulin resistance is thought to cause endothelial dysfunction,alveolar capillary micro-angiopathy and interstitial lung fibrosis through pro-inflammatory pathways.Autopsy studies have also demonstrated the presence of microvascular thrombi in affected sections of lung,which may be associated with diabetes.Chest imaging using x-ray(CXR)and computed tomography(CT)of chest is used to diagnose,assess disease progression and severity in COVID-19.This article reviews current literature regarding chest imaging findings in patients with diabetes affected by COVID-19.A literature search was performed on PubMed.Patients with diabetes infected with SARSCoV-2 are likely to have more severe infective changes on CXR and CT chest imaging.Severity of airspace consolidation on CXR is associated with higher mortality,particularly in the presence of co-morbidities such as ischaemic heart disease.Poorly controlled diabetes is associated with more severe acute lung injury on CT.However,no association has been identified between poorlycontrolled diabetes and the incidence of pulmonary thromboembolism in patients with COVID-19.
