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Phagocytosed Polyhedrin-Cytokine Cocrystal Nanoparticles Provide Sustained Secretion of Bioactive Cytokines from Macrophages

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BioDesign Research 2021年第1期2021卷 47-58页

作者： Astrid Wendler nicholas james Michael H.Jones Christian Pernstich Cell Guidance Systems Ltd. Maia BuildingBabraham Research CampusCambridge CB223ATUK

Many cells possess the ability to engulf and incorporate particles by *** active process is characteristic of microorganisms as well as higher order *** mammals,monocytes,macrophages,and microglia are among the so-called professional *** addition,cells such as fibroblast and chondrocytes are classified as nonprofessional *** phagocytes play important roles in both the innate and adaptive immune responses,wound healing,and tissue ***,these cells are increasingly studied as targets and vectors of therapeutic intervention to treat a range of *** phagocytes are notoriously difficult to transfect limiting their study and ***,efforts have shifted towards the development of nanoparticles to deliver a cargo to phagocytic cells via ***,this approach carries significant technical challenges,particularly for protein *** have focused on the development of nanoscale cocrystalline protein depots,known as PODS®,that contain protein cargos,including ***,we show that PODS are readily phagocytosed by nonprofessional as well as professional phagocytic cells and have attributes,such as highly sustained release of cargo,that suggest potential utility for the study and exploitation of phagocytic cells for drug *** and macrophages that ingest PODS retain normal characteristics including a robust chemotactic ***,the PODS-cytokine cargo is secreted by the loaded cell at a level sufficient to modulate the behavior of surrounding nonphagocytic *** results presented here demonstrate the potential of PODS nanoparticles as a novel molecular tool for the study and manipulation of phagocytic cells and for the development of Trojan horse immunotherapy strategies to treat cancer and other diseases.

关键词： sustained healing professional

The Influence of Culture and Biographical Variables on the Brand Image of Google and Baidu: An Exploratory Study in Guangzhou,China

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中国市场 2014年第9期 8-20页

作者： Rayne Cyla Handley nicholas james Raw Mattheus Louw Lynette Louw 罗德斯大学

The study found significant correlations between the culture dimensions of Confucian work dynamism,humanheartedness and moral discipline and the brand image dimensions of online search *** was also found that several significant relationships exist between the biographical variables of age and education and the brand image dimensions,and that culture and biographical variables have a linear relationship with brand *** findings highlight that culture and biographical information can influence Chinese consumer perceptions of an international or local *** thus need to align their brands with the culture and biographical profile of their target markets.

关键词： Cross - cultural management brand image China

A polarizing situation： Taking an in-plane perspective for next-generation near-field studies

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Frontiers of physics 2016年第2期11卷 1-17页

作者： P. james Schuck Wel Bao nicholas J. Borys Molecular Foundry Lawrence Berkeley National Laboratory Berkeley CA 94720 USA Department of Materials Science and Engineering University of California Berkeley CA 94720-1760 USA

By enabling the probing of light-matter interactions at the functionally relevant length scales of most materials, near-field optical imaging and spectroscopy accesses information that is unobtainable with other methods. The advent of apertureless techniques, which exploit the ultralocalized and enhanced near-fields created by sharp metallic tips or plasmonic nanoparticles, has resulted in rapid adoption of near-field approaches for studying novel materials and phenomena, with spatial resolution approaching sub-molecular levels. However, these approaches are generally limited by the dominant out-of-plane polarization response of apertureless tips, restricting the exploration and discovery of many material properties. This has led to recent design and fabrication breakthroughs in near-field tips engineered specifically for enhancing in-plane interactions with near-field light components. This mini-review provides a perspective on recent progress and emerging directions aimed at utilizing and controlling in-plane optical polarization, highlighting key application spaces where in-plane near-field tip responses have enabled recent advancements in the understanding and development of new nanostructured materials and devices.

关键词： near-field optical microscopy nano-optics TERS plasmonics optical antenna 2D materials

Combined risk modelling approach to identify the optimal carotid revascularisation approach

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Stroke & Vascular Neurology 2021年第3期6卷 476-482,I0080-I0084页

作者： james Francis Burke Lewis B Morgenstern nicholas H Osborne Rodney A Hayward Neurology University of Michigan Michigan MedicineAnn ArborMichiganUSA Vascular Surgery Univerity of Michigan MedicineAnn ArborMichiganUSA Internal Medicine University of Michigan Michigan MedicineAnn ArborMichiganUSA

Background Carotid endarterectomy(CEA)results in fewer perioperative strokes,but more myocardial infarctions(MI)than carotid artery stenting(CAS).We explored a combined modelling approach that stratifies patients by baseline stroke and *** Baseline registry-based risk models for perioperative stroke and MI were identified via literature *** then selected treatment risk models in the Carotid Revascularisation Stenting versus Endarterectomy(CREST)trial by serially adding covariates(baseline risk,treatment(CEA vs CAS),treatment-risk interaction and age-treatment interaction terms).Treatment risk models were externally validated using data from the Society for Vascular Surgery(SVS)Vascular Quality Initiative(VQI)CEA and carotid stenting registries and treatment models were recalibrated to the SVS-VQI *** net benefit was estimated by summing the predicted stroke and MI risk differences with CEA versus *** Perioperative treatment models had moderate predictiveness(c-statistic 0.69 for stroke and 0.68 for MI)and reasonable calibration across the risk spectrum for both stroke and MI within *** external validation in SVS-VQI,predictiveness was substantially reduced(c-statistic 0.61 for stroke and 0.54 for MI)and models substantially overpredicted *** patients(86.7%)were predicted to have net benefit from CEA in CREST(97.0%of symptomatic patients vs 75%of asymptomatic patients).Discussion A combined modelling approach that separates risk elements has potential to inform optimal ***,our current approach is not ready for clinical *** data support guidelines that suggest that CEA should be the preferred revascularisation modality in most patients with symptomatic carotid stenosis.

关键词： carotid Surgery optimal

Optimization of operational strategies for rich gas enhanced oil recovery based on a pilot test in the Bakken tight oil reservoir

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Petroleum Science 2023年第5期20卷 2921-2938页

作者： Xincheng Wan Lu Jin nicholas A.Azzolina Jin Zhao Xue Yu Steven A.Smith james A.Sorensen Energy&Environmental Research Center University of North Dakota15 North 23rd StreetStop 9018Grand ForksND58202-9018USA

Horizontal well drilling and multistage hydraulic fracturing have been demonstrated as effective approaches for stimulating oil production in the Bakken tight oil ***,after multiple years of production,primary oil recovery in the Bakken is generally less than 10%of the estimated original oil in *** huff‘n’puff(HnP)has been tested in the Bakken Formation as an enhanced oil recovery(EOR)method;however,most field pilot test results showed no significant incremental oil *** of the factors affecting HnP EOR performance is premature gas breakthrough,which is one of the most critical issues observed in the field because of the presence of interwell ***,injected gas rapidly reaches adjacent production wells without contacting reservoir rock and increasing oil *** conformance control is therefore needed to avoid early gas breakthrough and improve EOR *** this study,a rich gas EOR pilot in the Bakken was carefully analyzed to collect the essential reservoir and operational data.A simulation model with 16 wells was then developed to reproduce the production history and predict the EOR performance with and without conformance *** operational strategies,including single-and multiple-well HnP,with different gas injection constraints were *** simulation results of single-well HnP without conformance control showed that a rich gas injection rate of at least 10 MMscfd was needed to yield meaningful incremental oil *** strategy of conformance control via water injection could significantly improve oil production in the HnP well,but injecting an excessive amount of water also leads to water breakthrough and loss of oil production in the offset *** analyzing the production performance of the wells individually,the arrangement of wells was optimized for multiple-well HnP *** multiwell results showed that rich gas EOR could improve oil production up to 7.4%by employing confor

关键词： Rich gas injection Bakken tight oil reservoir EOR strategies Conformance control Embedded discrete fracture model

Hemobilia: Etiology, diagnosis, and treatment

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Liver Research 2018年第4期2卷 200-208页

作者： Rani Berry james Han Ani A.Kardashian nicholas F.LaRusso james H.Tabibian Department of Internal Medicine UCLA Ronald Reagan Medical CenterLos AngelesCAUSA Department of Internal Medicine University of California IrvineIrvineCAUSA UCLA Gastroenterology Fellowship Training Program Vatche and Tamar ManoukianDivision of Digestive DiseasesLos AngelesCAUSA Division of Gastroenterology and Hepatology Mayo ClinicRochesterMNUSA Division of Gastroenterology Department of MedicineOlive View-UCLA Medical CenterSylmarCAUSA

Hemobilia refers to bleeding from and/or into the biliary tract and is an uncommon but important cause of gastrointestinal *** of hemobilia date back to the 1600s,but due to its relative rarity and challenges in diagnosis,only in recent decades has hemobilia been more critically *** majority of cases of hemobilia are iatrogenic and caused by invasive procedures involving the liver,pancreas,bile ducts and/or the hepatopancreatobiliary vasculature,with trauma and malignancy rep-resenting the two other leading causes.A classic triad of right upper quadrant pain,jaundice,and overt upper gastrointestinal bleeding has been described(***'s triad),but this is present in only 25%e30%of patients with ***,prompt diagnosis depends critically on having a high index of suspicion,which may be based on a patient's clinical presentation and having recently undergone(peri-)biliary instrumentation or other predisposing *** treatment of hemobilia depends on its severity and suspected source and ranges from supportive care to advanced endoscopic,interventional radiologic,or surgical *** we provide a clinical overview and update regarding the eti-ology,diagnosis,and treatment of hemobilia geared for specialists and subspecialists alike.

关键词： Hemobilia Upper gastrointestinal hemmorhage Etiology Diagnosis Imaging Hepatopancreatobiliary interventions

Nonlinear Model of Mean Free Surface of Waves

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China Ocean Engineering 1999年第2期14卷 155-162页

作者： nicholas DODD Ph. D. Coastal Group HR Wallingford Howbery Park Wallingford

A nonlinear model of mean free surface of waves or wave set-up is presented. The model is based on that of Roelvink (1993), but the numerical techniques used in the solution are based on the Weighted-Average Flux (WAF) method (Watson el al., 1992), with Time-Operator-Splitting (TOS) used for the treatment of the source terms. This method allows a small number of computational points to be used, and is particularly efficient in modeling wave set-up. The short wave (or primary wave) energy equation is solved by use of a more traditional Lax-Wendroff technique. A nonlinear wave theory (james, 1974) is introduced. The model described in this paper is found to be satisfactory in most respects when compared with the measurements conducted by Stive (1983) except in modeling the mean free surface very close to the mean shoreline.

关键词： mean free surface radiation stress hyperbolic wave theory nonlinear model wave propagation

The Weng'an biota and the Ediacaran radiation of multicellular eukaryotes

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National Science Review 2014年第4期1卷 498-520页

作者： Shuhai Xiao A.D.Muscente Lei Chen Chuanming Zhou james D.Schiffbauer Andrew D.Wood nicholas F.Polys Xunlai Yuan Department of Geosciences Virginia Polytechnic Institute and State University State Key Laboratory of Palaeobiology and Stratigraphy Nanjing Institute of Geology and Paleontology Chinese Academy of Sciences College of Earth Science University of Chinese Academy of Sciences Key Laboratory of Economic Stratigraphy and Palaeogeography Nanjing Institute ofGeology and Paleontology Chinese Academy of Sciences Department of Geological Sciences University of Missouri Advanced Research Computing Virginia Polytechnic Institute and State University

The rise of multicellularity represents a major evolutionary transition and it occurred independently in multiple eukaryote *** simple multicellular organisms may have evolved in the Mesoproterozoic Era or even earlier,complex multicellular eukaryotes began to diversify only in the Ediacaran Period,just before the Cambrian ***,the Ediacaran fossil record can provide key paleontological evidence about the early radiation of multicellular eukaryotes that ultimately culminated in the Cambrian *** Ediacaran Weng’an biota in South China hosts exceptionally preserved eukaryote fossils,including various acanthomorphic acritarchs,pseudoparenchymatous thalli,tubular microfossils,and spheroidal fossils such as Megasphaera,Helicoforamina,Spiralicellula,and *** of these fossils have been interpreted as multicellular eukaryotes,although alternative interpretations have also been *** this review,we critically examine these various interpretations,focusing particularly on Megasphaera,which has been variously interpreted as a sulfur-oxidizing bacterium,a unicellular protist,a mesomycetozoean-like holozoan,a volvocine green alga,a stem-group animal,or a crown-group *** conclude that Megasphaera is a multicellular eukaryote with evidence for cell-to-cell adhesion,a lexible membrane unconstrained by a rigid cell wall,spatial cellular diferentiation,germ–soma separation,and programmed cell *** features are inconsistent with the bacterium,unicellular protist,and mesomycetozoean-like holozoan ***,the surviving hypotheses,particularly the stem-group animal and algal interpretations,should be further tested with additional *** Weng’an biota also hosts cellularly diferentiated pseudoparenchymatous thalli with specialized reproductive structures indicative of an ainity with lorideophyte red *** other Weng’an fossils reviewed here may also be multicellular eukaryotes,although direct cellular evidenc

关键词： Ediacaran Period Doushantuo Formation Weng’an biota multicellularity eukaryotes animals algae

Predicting systemic spread in early colorectal cancer: Can we do better?

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World Journal of Gastroenterology 2019年第23期25卷 2887-2897页

作者： Scarlet Fiona Brockmoeller nicholas Paul West Pathology and Data Analytics Leeds Institute of Medical Research at St.James’sUniversity of LeedsSchool of MedicineLeeds LS97TFUnited Kingdom

Through the implementation of national bowel cancer screening programmes we have seen a three-fold increase in early pT1 colorectal cancers, but how these lesions should be managed is currently unclear. Local excision can be an attractive option, especially for fragile patients with multiple comorbidities, but it is only safe from an oncological point of view in the absence of lymph node metastasis. Patient risk stratification through careful analysis of histopathological features in local excision or polypectomy specimens should be performed according to national guidelines to avoid under-or over-treatment. Currently national guidelines vary in their recommendations as to which factors should be routinely reported and there is no established multivariate risk stratification model to determine which patients should be offered major resectional *** histopathological parameters such as tumour grading or lymphovascular invasion have been shown to be predictive of lymph node metastasis in a number of studies but the inter-and intra-observer variation in reporting is high. Newer parameters including tumour budding and poorly differentiated clusters have been shown to have great potential, but again some improvement in the inter-observer variation is required. With the implementation of digital pathology into clinical practice, quantitative parameters like depth/area of submucosal invasion and proportion of stroma can be routinely assessed. In this review we present the various histopathological risk factors for predicting systemic spread in pT1 colorectal cancer and introduce potential novel quantitative variables and multivariable risk models that could be used to better define the optimal treatment of this increasingly common disease.

关键词： Early colorectal cancer Bowel cancer screening Local resection Major resection Morphological risk factors Conventional histopathology parameters Novel histopathology parameters Risk stratification models Digital pathology