13,038 research outputs found

    New Tool for Rapid and Accurate Detection of Interleukin-2 and Soluble Interleukin-2 Receptor α in Cancer Diagnosis Using a Bioresponsive Microgel and Multivalent Protein Binding

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    © Interleukin-2 (IL-2) and its α receptor in soluble form (sIL-2Rα) are considered biomarkers for cancers and immune-related diseases. Enzyme-linked immunosorbent assay is the most common method used to evaluate biomarkers in clinical practice; it is precise but time-consuming and involves complicated procedures. Here, we have developed a rapid yet accurate modality for cancer diagnosis that enables on-site evaluation of cancer markers, that is, IL-2 and sIL-2Rα, without complicated pretreatment of cancer patient-derived blood samples. Surface plasmon resonance and bioresponsive microgels conjugated with IL-2 receptors, that is, IL-2Rβ and IL-2Rγ, were utilized to measure IL-2 and sIL-2Rα levels via multivalent protein binding (MPB) between the ligands and their receptors. Our results showed that this novel method enables us to perform cancer diagnosis with a 1000-fold dilution of serum in 10 min. The advantage of MPB-based cancer diagnosis originates from its great selectivity for a target molecule and tolerance to a myriad of nonspecific substances in serum, which allows on-site clinical evaluation. Importantly, our finding implies that MPB-based cancer diagnosis provides a new paradigm not only for improving cancer treatment but also for evaluating a target molecule in unpurified and complex solutions such as blood.11Nsciescopu

    Author Correction: Human fingerprint in global weather

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    In the version of this News & Views originally published, the ref. 5 author surnames Meihnausen, Fisher and Szekely were spelled incorrectly; they should have been spelled Meinshausen, Fischer and Székely, respectively. This has now been corrected. © 2020, Springer Nature Limited.11Nsciessciscopu

    Label-Free Analysis of Multivalent Protein Binding Using Bioresponsive Nanogels and Surface Plasmon Resonance (SPR)

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    Precise identification of protein-protein interactions is required to improve our understanding of biochemical pathways for biology and medicine. In physiology, how proteins interact with other proteins or small molecules is crucial for maintaining biological functions. For instance, multivalent protein binding (MPB), in which a ligand concurrently interacts with two or more receptors, plays a key role in regulating complex but accurate biological functions, and its interference is related to many diseases. Therefore, determining MPB and its kinetics has long been sought, which currently requires complicated procedures and instruments to distinguish multivalent binding from monovalent binding. Here, we show a method for quickly evaluating the MPB over monovalent binding and its kinetic parameters in a label-free manner. Engaging pNIPAm-co-AAc nanogels with MPB-capable moieties (e.g., PD-1 antigen and biocytin) permits a surface plasmon resonance (SPR) instrument to evaluate the MPB events by amplifying signals from the specific target molecules. Using our MPB-based method, PD-1 antibody that forms a type of MPB by complexing with two PD-1 proteins, which are currently used for cancer immunotherapy, is detectable down to a level of 10 nM. In addition, small multivalent cations (e.g., Ca2+, Fe2+, and Fe3+) are distinguishably measurable over monovalent cations (e.g., Na+ and K+) with the pNIPAm-co-AAc nanogels.N

    The practice of access pricing : telecommunications in the United Kingdom

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    Telecommunications was the first network utility to be privatized in the United Kingdom. Drawing on 15 years'experience and discussion in the field, the author shows the economic principles of regulation in general and access pricing in particular that have been implemented. British Telecommunications (BT), formed as a public enterprise in 1980-81, was privatized in 1984. Since then the approaches to regulation have changed in three broad periods: the duoply, the transition to competition, and the recently introduced normalization phase. Dealing with each period, the author focuses on how the actual implementation of access charges are determined, at the same time providing background needed on regulatory intervention generally. Rather than follow the model of competition for a common infrastructure, Oftel [the Office of Telecommunications, the regulatory agency]has encouraged competition between alternative networks, which benefits customers but involves duplication of fixed costs. As a result of Oftel's approach, customers have seen their bills reduced 50 percent in real terms since privatization. It is difficult to know how much to attribute this remarkable result to technological progress (BT halved its workforce in the same period), to regulatory intervention (Oftel set string caps until 1997), or to competition (there are hundreds of players in the market). The author contends more weight should probably be given to the first two. Entrants have not achieved big market shares, if one considers the asymmetric regulation that has been in place for more than a decade. Indirectly, at least, competition benefited consumers by applying discipline to BT's behavior. Oftel's approach was interventionist until 1997, when it began trying to normalize the industry, as authority overseeing competition. The odds on complete deregulation are slight, and some controls on industry will remain. In the longer term, Oftel should especially monitor anticompetitive practices and collusive behavior among the bigger players (BT, CWC, and cellulator operators), The United Kingdom's interconnection experience demonstrates the complexity of the problem and its relationship to other topics, such as tariff rebalancing, access deficit, and universal service. Although a bit ad hoc, the recent incentive regulation, with a network cap based on proper accounting procedures and engineering models, may represent the best practice available today in the telecommunications industry, says the author.Public Sector Economics&Finance,Decentralization,Knowledge Economy,Economic Theory&Research,Payment Systems&Infrastructure,Public Sector Economics&Finance,Education for the Knowledge Economy,Knowledge Economy,Economic Theory&Research,ICT Policy and Strategies

    Functions of autoreception: Karl Ove Knausgård as author-critic and rewriter

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    Karl Ove Knausgård made his entry into the literary field as a critic in the 1990s, and he has since 1998 made his mark as a novelist and essayist. The six-volume autobiographical work Min kamp (2009-2011) is in essence about what it means for him to be an author. This thesis investigates Knausgård’s strategies as a critic, essayist, and as the author of Min kamp to position himself and his poetics within the literary field and a literary tradition. Specifically, it examines the functions of autoreception, i.e. self-criticism, implicit in Knausgård’s role as an author-critic, an author who writes literary criticism, and as a rewriter, an author who rewrites his own texts and the context and poetic intentions of his previous texts. Thus, this thesis aims to answer the question what are the functions of criticism and of rewriting for Karl Ove Knausgård as an author? Part I outlines a new framework of autoreception devised for examining the functions of criticism and rewriting. The proposed common denominator is that both function to establish, position, and validate an author-image. Ultimately, a new understanding of the narration in Min kamp as autoreceptive is offered. Part II examines a largely unexplored area of Knausgård’s work, namely the strategies of Knausgård as a critic prior to publishing his first novel, and how Knausgård rewrites himself during this period in Min kamp. Part III focuses on Knausgård’s rewriting of the period between writing his second novel and up until he begins writing Min kamp. It investigates the strategic functions of the narrative structure, the functions of the essayistic and critical passages, and the functions of the distance and unity between past and present author-images that Knausgård creates in his rewriting. This thesis thus aims to contribute to the scholarship regarding Karl Ove Knausgård by conducting an author-study that examines the relationship between criticism and poetics. In addition, it aims to contribute to a broader field of research by offering a theoretical and methodological framework of autoreception, which works across the boundaries of critical, essayistic, and literary texts

    [[alternative]]CREATE YOUR OWN FATE :TWO RUNNER’S LIFE STORY

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    [[abstract]]CREATE YOUR OWN FATE : TWO RUNNER’S LIFE STORY Master’s Thesis, June, 2006 Wu, Bae-Chyi Advisor: Liu, I-Min Ph.D. Abstract “Running is the Way for Runner to Achieve Self-Realization and Mental Fortitude”. This article explored two runners’ experiences of marathon running and presented through the telling of life’s stories. To experience personally what inspirations running could bring to life, the author chose running as a total novice. From the initial physical and mental anguish, struggle and through continual adaptation, training and retrospection, the author gradually discovered the fun of running and the wide spectrum of emotions it generated - tranquility, flowing, soul-searching, torment, bondage, contradiction…etc. These voices enriched and changed the life of the author in a subtle way. The author was also able to discern life’s philosophies in the process. In the lapse of time, the author reviewed his own life story back and forth, and shared the story of runner Ahdar. He re-discovered himself, re-acquainted with himself, and realized that he still held many dreams and that running was a goal he could achieve. The temple of marathon is a symbol. Stepping into this temple is as if breaking through the cocoon in a rebirth, during which pain is a part of the experience. The pain suffered during training for marathon helps accumulate the strength to face future challenges. A person who has completed the pilgrimage of marathon will be likely to gain greater strength to realize other dreams in life. Key words: Running, Runner, Life story

    Anchee Min and Elif Armbruster discuss, The Chinese-American Dream at Ford Hall Forum, video recording, 5/23/2013

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    Twenty years after penning her first memoir on growing up in China during the Cultural Revolution, author Anchee Min now releases The Cooked Seed: the true story of her journey to, and within, America. Min draws us in to bear witness to her trek from a land of deprivation to one of surrounding bounty that is just out of her reach. She works five jobs at once and suffers rape, exhaustion, and divorce. As these revolutionary personal events shape her world view, they culminate in the biggest shift of all: the birth of her daughter. Moderator Elif Armbruster (Associate Professor of English, Suffolk University) helps Min present her unique immigration narrative within the universal struggle of building a life despite precious few fundamental tools. Anchee Min will be signing and selling copies of her book, The Cooked Seed, at the end of the event.https://dc.suffolk.edu/fhf-av/1131/thumbnail.jp

    Extrusion foaming of bioplastics for lightweight structure in food packaging

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    This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.This thesis reports the systematic approaches to overcome the key drawbacks of the pure PHBV, namely low crystallisation rate, tensile strength, ductility, melt viscosity, thermal stability and high materials cost. The physical, mechanical, thermal, and rheological properties of the pure PHBV were studied systematically first to lay a solid foundation for formulation development. The influence of blending with other biopolymers, inclusion of filler, and chain extender additives in terms of mechanical properties, rheology, thermal decomposition and crystallization kinetics were then followed. Creating lightweight structures by foaming is considered to be one of the effective ways to reduce material consumption, hence the reduction of density and morphology of PHBV-based foams using extrusion foaming technique were studied comprehensively in terms of extrusion conditions (temperature profiles, screw speed and material feeding rate) and the blowing agent content. The material cost reduction was achieved by adding low-cost filler (e.g. CaCO3) and reduction of density by foaming. The thermal instability was enhanced by incorporation of chain extender (e.g. Joncryl) and blending with a high thermal stability biopolymer (e.g. PBAT). The polymer blend also improved the ductility. Adding nucleation agent enhanced the crystallization rate to reduce stickiness of extruded sheet. The final formulation (PHBV/PBAT/CaCO3 composite) was successfully extruded into high quality sheet and thermoformed to produce prototype trays in an industrial scale trial. The effect of the extrusion conditions (temperature profiles, screw speed and material feeding rate) and the blowing agent content are correlated to the density reduction of the foams. 61 and 47 % density reduction were achieved for the commercial PHBV and the PHBV/PBAT/CaCO3 composite respectively and there exists further scope for more expansion if multiple variable optimisation of the conditions are carried out.This study is funded by the UK Government Department of Trade & Industry (Technology Strategy Board), as part of the project “Biobased Lightweight Sandwich Structures for Packaging Applications”

    Tuning Surface Plasmon Resonance Responses through Size and Crosslinking Control of Multivalent Protein Binding-Capable Nanoscale Hydrogels

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    © 2022 American Chemical Society.Surface plasmon resonance (SPR) phenomena have been widely studied to detect biomolecules because of their high sensitivity and ability to determine biomolecular interactions with kinetic information. However, highly selective detection in specific concentration ranges relevant to target biomolecules is still a challenging task. Recently, we developed bioresponsive nanoscale hydrogels to selectively intensify SPR signals through multivalent protein binding (MPB) events with target biomolecules, including IL-2, where we were able to demonstrate exceptional selectivity for target biomolecules with minimal responses to nonspecific and monovalent binding events. In this work, we systematically explored the relationship between the physical properties of MPB-capable nanoscale hydrogels and their SPR response induced in the presence of the programmed cell death protein 1 antibody (PD-1Ab) as a model target biomolecule. First, we developed a synthetic protocol by controlling various reaction parameters to construct a library of nanoscale poly(N-isopropylacrylamide-co-acrylic acid) hydrogels (NHs) with different sizes (from 400 nm to 1 μm) and degrees of crosslinking (from 2 to 8%). Then, by incorporating MPB-capable PD-1 receptors onto the surface of NHs to form PD-1-responsive nanoscale hydrogels (PNHs), the hydrogel size and crosslinking dependency of their SPR responses were investigated. Our results reveal the appropriate hydrogel size regime and degree of crosslinking for effective PD-1Ab detection at specific concentrations range between a few nM and 1 μM. Overall, our study demonstrates that by tuning the physical properties of the nanoscale hydrogel matrix, the sensitivity and detection range of MPB-based SPR sensors can be modulated to potentially benefit clinical applications such as monitoring diverse therapeutic biomolecules.11Nsciescopu

    Quantitative analysis of surface wave patterns of Min proteins

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    The Min protein system is arguably the best-studied model system for biological pattern formation. It exhibits pole-to-pole oscillations in E. coli bacteria as well as a variety of surface wave patterns in in vitro reconstitutions. Such Min surface wave patterns pose particular challenges to quantification as they are typically only semi-periodic and non-stationary. Here, we present a methodology for quantitatively analysing such Min patterns, aiming for reproducibility, user-independence, and easy usage. After introducing pattern-feature definitions and image-processing concepts, we present an analysis pipeline where we use autocorrelation analysis to extract global parameters such as the average spatial wavelength and oscillation period. Subsequently, we describe a method that uses flow-field analysis to extract local properties such as the wave propagation velocity. We provide descriptions on how to practically implement these quantification tools and provide Python code that can directly be used to perform analysis of Min patterns.BN/Cees Dekker La
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