► Ligand binding analysis by fluorescence quenching methodology is often performed incorrectly. ► Typical pitfalls of the methodology and potential impacts are discussed. ► Proper methodology is ...briefly indicated. ► Many articles will require re-evaluation.
In recent years fluorescence quenching has become a popular tool to investigate various aspects of ligand binding. Unfortunately, various pitfalls are often overlooked in a large number of papers, published in many different journals. In this criticism we discuss a number of possible mistakes and show how they may affect the data and their analysis. Moreover, we point to problems in the understanding of the fundamentals of fluorescence quenching, and show direct contradictions within many of these papers. This review hopefully contributes to a re-appraisal of the published literature and to a more appropriate use of fluorescence quenching to study ligand binding.
The forward–backward splitting method (FBS) for minimizing a nonsmooth composite function can be interpreted as a (variable-metric) gradient method over a continuously differentiable function which ...we call forward–backward envelope (FBE). This allows to extend algorithms for smooth unconstrained optimization and apply them to nonsmooth (possibly constrained) problems. Since the FBE can be computed by simply evaluating forward–backward steps, the resulting methods rely on a similar black-box oracle as FBS. We propose an algorithmic scheme that enjoys the same global convergence properties of FBS when the problem is convex, or when the objective function possesses the Kurdyka–Łojasiewicz property at its critical points. Moreover, when using quasi-Newton directions the proposed method achieves superlinear convergence provided that usual second-order sufficiency conditions on the FBE hold at the limit point of the generated sequence. Such conditions translate into milder requirements on the original function involving generalized second-order differentiability. We show that BFGS fits our framework and that the limited-memory variant L-BFGS is well suited for large-scale problems, greatly outperforming FBS or its accelerated version in practice, as well as ADMM and other problem-specific solvers. The analysis of superlinear convergence is based on an extension of the Dennis and Moré theorem for the proposed algorithmic scheme.
Human serum albumin (HSA) is characterized by 17 disulfides and by only one unpaired cysteine (Cys34), which can be free in the reduced albumin or linked as a mixed disulfide with cysteine, or in ...minor amount with other natural thiols, in the oxidized albumin. In healthy subjects, the level of the oxidized form is about 35%, but it rises up to 70% after oxidative insults or in patients with kidney diseases. Oxidized albumin is therefore considered a short‐term biomarker of oxidative stress as its level may increase or decrease under appropriate redox inputs in discrete temporal spans. This paper defines, for the first time, the kinetic properties of reduced and oxidized Cys34 of HSA in their reactions with natural disulfides and thiols. Kinetic constants support the evidence that the Cys34 redox oscillations observed in vivo are mainly due to the interaction with cysteine and cystine without the involvement of any enzymatic support. This study gives also a plausible explanation for the absence of involvement of the 17 disulfides naturally present in HSA in these redox transitions. This inert behavior toward cysteine is marginally due to solvent accessibility or flexibility factors of these bonds but mainly to their strong thermodynamic stability, which is caused essentially by a proximity effect. A similar mechanism is likely at play in the many proteins that maintain disulfide bridges in a reducing medium like the cytosol.
Human serum albumin shows 17 disulfides and one unpaired Cys34 which can be free in the reduced albumin or linked as a mixed disulfide in the oxidized albumin. Kinetic constants support the evidence that the Cys34 redox oscillations observed in vivo are mainly due to the interaction with cysteine and cystine without the involvement of any enzymatic support.
Although the performance of popular optimization algorithms such as the Douglas–Rachford splitting (DRS) and the ADMM is satisfactory in convex and well-scaled problems, ill conditioning and ...nonconvexity pose a severe obstacle to their reliable employment. Expanding on recent convergence results for DRS and ADMM applied to nonconvex problems, we propose two linesearch algorithms to enhance and robustify these methods by means of quasi-Newton directions. The proposed algorithms are suited for nonconvex problems, require the same black-box oracle of DRS and ADMM, and maintain their (subsequential) convergence properties. Numerical evidence shows that the employment of L-BFGS in the proposed framework greatly improves convergence of DRS and ADMM, making them robust to ill conditioning. Under regularity and nondegeneracy assumptions at the limit point, superlinear convergence is shown when quasi-Newton Broyden directions are adopted.
We propose a Newton-type alternating minimization algorithm (NAMA) for solving structured nonsmooth convex optimization problems where the sum of two functions is to be minimized, one being strongly ...convex and the other composed with a linear mapping. The proposed algorithm is a line-search method over a continuous, real-valued, exact penalty function for the corresponding dual problem, which is computed by evaluating the augmented Lagrangian at the primal points obtained by alternating minimizations. As a consequence, NAMA relies on exactly the same computations as the classical alternating minimization algorithm (AMA), also known as the dual-proximal gradient method. Under standard assumptions, the proposed algorithm converges with global sublinear and local linear rates, while under mild additional assumptions, the asymptotic convergence is superlinear, provided that the search directions are chosen according to quasi-Newton formulas. Due to its simplicity, the proposed method is well suited for embedded applications and large-scale problems. Experiments show that using limited-memory directions in NAMA greatly improves the convergence speed over AMA and its accelerated variant.
The state participates in shaping and transmitting citizenship. From a European outlook, this special Issue of Politics & Policy focuses on the role of public policy, according to a comparative and ...multisectorial perspective. The special Issue originated in a Panel held on September 4, 2019 at the European Consortium of Political Research's General Conference, at the University of Wroclaw, Poland. The articles in this special Issue draw from a plurality of methods, from sociohistory to policy ethnography, and analyze how the state, in the concrete conception and implementation of its action, is a producer of social categorizations determining the legitimate contours of citizenship. Altogether, the case studies in this issue allow us to scrutinize the government of and by citizenship, meanwhile identifying discrepancies and invariants in Europe.
Related Articles in this Special Issue:
Barrault‐Stella, Lorenzo, and Thomas Douniès. 2021. “From Good ‘User’ to Good Citizen? The Political Effects on Families of Education Policies in France.” Politics & Policy 49 (4).
Ewert, Benjamin. 2021. “Citizenship as a Form of Anticipatory Obedience? Implications of Preventive Health Policy in Germany.” Politics & Policy 49 (4).
Skowronska, Kaja. 2021. “The Recent Politicization of Immigration in Poland in Light of Preexisting State Practices: Continuity or Change in the Understanding of Citizenship and Nationhood?” Politics & Policy 49 (4).
Introducción al número especial: La ciudadanía como herramienta de gobierno en Europa
El estado participa en la formación y transmisión de la ciudadanía. Desde una perspectiva europea, este número especial de Politics & Policy se centra en el papel de las políticas públicas, desde una perspectiva comparativa y multisectorial. El número especial se originó en un Panel celebrado el 4 de septiembre de 2019 en la Conferencia General del Consorcio Europeo de Investigación Política (ECPR), en la Universidad de Wroclaw, Polonia. Los cinco artículos de este número especial parten de una pluralidad de métodos, desde la sociohistoria hasta la etnografía política, y analizan cómo el Estado, en la concepción e implementación concretas de su acción, es un productor de categorizaciones sociales que determinan los contornos legítimos de la ciudadanía. En conjunto, los estudios de caso en este número nos permiten escudriñar el gobierno de y por ciudadanía, mientras identificamos discrepancias e invariantes en Europa.
特刊导论：充当政府工具的欧洲公民身份
国家在影响和传播公民身份一事上发挥作用。本期《政治与政策》特刊透过比较视角和多部门视角，聚焦于欧洲公共政策的作用。本期内容源于2019年9月4日欧洲政治研究联合会（ECPR）在波兰弗罗茨瓦夫大学举办的一次专家讨论会。本期特刊收录的5篇文章采用了包括社会历史和政策民族志在内的多种方法，并分析了国家在具体行动构建和执行一事中如何产生社会分类，后者决定了公民身份的合法定义。整体而言，本期的案例研究允许我们分析公民身份的治理和由公民身份产生的体制，同时识别了欧洲不同地区的差异和共同点。
Selective targeting is a crucial property of nanocarriers used for drug delivery in cancer therapy. We generated biotinylated octahedral DNA nanocages functionalized with folic acid through ...bio-orthogonal conjugation chemistry. Molecular modelling indicated that a distance of about 2.5 nm between folic acid and DNA nanocage avoids steric hindrance with the folate receptor. HeLa cells, a folate receptor positive tumour cell line, internalize folate-DNA nanocages with efficiency greater than 40 times compared to cells not expressing the folate receptors. Functionalized DNA nanocages are highly stable, not cytotoxic and can be efficiently loaded with the chemotherapeutic agent doxorubicin. After entry into cells, doxorubicin-loaded nanoparticles are confined in vesicular structures, indicating that DNA nanocages traffic through the endocytic pathway. Doxorubicin release from loaded DNA cages, facilitated by low pH of endocytic vesicles, induces toxic pathways that, besides selectively killing folate receptor-positive cancer cells, leads to cage degradation avoiding nanoparticles accumulation inside cells.
Folate-functionalized octahedral DNA nanocages, loaded with doxorubicin (Dox) (Dox-loaded cage), deliver the drug selectively to cancer cells expressing the α isoform of the folate receptor (αFR). Dox, released from loaded DNA cages inside cells, induces a cytotoxic effect higher than free Dox administered at the same concentration and leads to intracellular DNA nanocage degradation, avoiding the problem of nanocarrier accumulation in vivo. Display omitted
This article analyzes the contribution of education policies to the shaping of citizenship in France. We connect two inquiries. The first, about Moral and Civic Teaching, is a case of policy ...intentionally devoted to convey civic norms. The second, about the ordinary government of parents, concerns diffuse civic socialization at school. We ask how, and to what extent, the political order of school—composed of policy programs and institutional routines—builds civic behaviors throughout an intertwinement between school‐related norms and citizenship standards. The analysis mainly relies on qualitative data—hundreds of interviews and ethnography—taking into account various contexts in France regarding the schools and the geographic situations. Education policies not only appear central in the definition of civic norms and the “good” ways of acting politically in France, but may also be critical in other democratic systems where school plays a comparable role in the socialization to and by the state.
Related Articles in this Special Issue
Barrault‐Stella, Lorenzo, and Thomas Douniès. 2021. “Introduction to the Special Issue: Citizenship as a Tool of Government in Europe.” Politics & Policy 49 (4).
Haapajärvi, Linda. 2021. “On the Importance of Playing House: Belonging Work and the Making of Relational Citizens in Finnish Immigrant Integration Policies.” Politics & Policy 49 (4).
Skowronska, Kaja. 2021. “The Recent Politicization of Immigration in Poland in Light of Preexisting State Practices: Continuity or Change in the Understanding of Citizenship and Nationhood?” Politics & Policy 49 (4).
¿De buen “usuario” a buen ciudadano? Los efectos políticos en las familias de las políticas educativas en Francia
Este artículo analiza la contribución de las políticas educativas a la formación de la ciudadanía en Francia. Conectamos dos consultas. El primero, sobre Enseñanza moral y cívica, es un caso de política intencionalmente dedicada a transmitir normas cívicas. El segundo, sobre el gobierno ordinario de los padres, se refiere a la socialización cívica difusa en la escuela. Preguntamos cómo, y en qué medida, el orden político de la escuela—compuesto por programas de políticas y rutinas institucionales—construye comportamientos cívicos a través de un entrelazamiento entre las normas relacionadas con la escuela y los estándares de ciudadanía. El análisis se basa principalmente en datos cualitativos, cientos de entrevistas y etnografía, teniendo en cuenta varios contextos en Francia con respecto a las escuelas y las situaciones geográficas. Las políticas educativas parecen ser centrales en la definición de normas cívicas y las “buenas” formas de actuar políticamente en Francia, pero también pueden ser críticas en otros sistemas democráticos donde la escuela juega un papel comparable en la socialización hacia y por el estado.
从好“用户”到好公民？法国教育政策对家庭产生的政治影响
本文分析了法国教育政策对公民身份形成产生的影响。我们将两项调查相联系。第一项调查有关于道德和公民教学（Moral and Civic Teaching）作为传递公民规范的政策案例。第二项调查有关于学校为扩散公民社会化而对父母所作的一般安排。我们研究了学校的政治指令—由政策计划和制度惯例组成—如何以及在多大程度上通过“学校相关规范和公民身份标准之间的互动”建立公民行为 。分析主要依赖由上千次访谈和民族志组成的定性数据，将关于法国学校和地理情况的不同情境考虑在内。教育政策在法国公民规范定义和“良好”政治行动方式中似乎是关键的，但可能在其他相似民主系统中也是如此。
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