Since the 16th century, assays and screens have been essential for scientific investigation. However, most methods could be significantly improved, especially in accuracy, scalability, and often lack adequate comparisons to negative controls. There is a lack of consistency in distinguishing assays, in which accuracy is the main goal, from screens, in which scalability is prioritized over accuracy. We dissected and modernized the original definitions of assays and screens based upon recent developments and the conceptual framework of the original definitions. All (...) methods have three components: design/measurement, performance, and interpretation. We propose a model of method development in which reproducible observations become new methods, initially assessed by sensitivity. Further development can proceed along a path to either screens or assays. The screen path focuses on scalability first, but can later prioritize analysis of negatives. Alternatively, the assay path first compares results to negative controls, assessing specificity and accuracy, later adding scalability. Both pathways converge on a high‐accuracy and throughput (HAT) assay, like next generation sequencing, which we suggest should be the ultimate goal of all testing methods. Our model will help scientists better select among available methods, as well as improve existing methods, expanding their impact on science. (shrink)

The paper introduces the concept of B-Almost distributive fuzzy lattice in terms of its principal ideal fuzzy lattice. Necessary and sufficient conditions for an ADFL to become a B-ADFL are investigated. We also prove the equivalency of B-algebra and B-fuzzy algebra. In addition, we extend PSADL to PSADFL and prove that B-ADFL implies PSADFL.

In this paper, we introduce the notion of intuitionistic fuzzy PMS-subalgebras under homomorphism and Cartesian product and investigate several properties. We study the homomorphic image and inverse image of the intuitionistic fuzzy PMS-subalgebras of a PMS-algebra, which are also intuitionistic fuzzy PMS-subalgebras of a PMS-algebra, and find some other interesting results. Furthermore, we also prove that the Cartesian product of intuitionistic fuzzy PMS-subalgebras is again an intuitionistic fuzzy PMS-subalgebra and characterize it in terms of its level sets. Finally, we consider (...) the strongest intuitionistic fuzzy PMS-relations on an intuitionistic fuzzy set in a PMS-algebra and demonstrate that an intuitionistic fuzzy PMS-relation on an intuitionistic fuzzy set in a PMS-algebra is an intuitionistic fuzzy PMS-subalgebra if and only if the corresponding intuitionistic fuzzy set in a PMS-algebra is an intuitionistic fuzzy PMS-subalgebra of a PMS-algebra. (shrink)

In February 2010, the World Medical Association hosted an international symposium on the ethics of placebo controls in clinical trials (WMA 2010). Despite years of debate, ethicists, clinical trialists, and policy makers remain divided over the ethical acceptability of using placebos in research when a proven, effective treatment is available. The protracted nature of this problem is due, at least in part, to a perceived conflict between the opposing demands placed on clinical research by science and ethics. A good, scientifically (...) valid trial, it is argued, must be “assay sensitive,” and without using a placebo control, there can be no guarantee that it is. In this article, we revisit some of the claims made about .. (shrink)

ADP‐ribosylation is a post‐translational modification catalyzed by writer enzymes – ADP‐ribosyltransferases. The modification is part of many signaling events, can modulate the function and stability of target proteins, and often results in the recruitment of reader proteins that bind to the ADP‐ribosyl groups. Erasers are integral actors in these signaling events and reverse the modification. ADP‐ribosylation can be targeted with therapeutics and many inhibitors against writers exist, with some being in clinical use. Inhibitors against readers and erasers are sparser and (...) development of these has gained momentum only in recent years. Drug discovery has been hampered by the lack of specific tools, however many significant advances in the methods have recently been reported. We discuss assays used in the field with a focus on methods allowing efficient identification of small molecule inhibitors and profiling against enzyme families. While human proteins are focused, the methods can be also applied to bacterial toxins and virus encoded erasers that can be targeted to treat infectious diseases in the future. (shrink)

In this paper, we take up two objections Raymond Geuss levels against John Rawls′ ideal theory in Philosophy and Real Politics. We show that, despite their fundamental disagreements, the two theorists share a common starting point: they both reject doing political philosophy by way of applying an independently derived moral theory; and grapple with the danger of unduly privileging the status quo. However, neither Rawls′ characterization of politics nor his ideal theoretical approach as response to the aforementioned danger is adequate (...) or so we argue. Moreover, contrary to received opinion, Geuss′ political philosophy is the more reflective and the more philosophical of the two. In a final section, we highlight another agreement: both think that political philosophers should develop conceptual innovations as a way of clarifying and overcoming practical problems. We demonstrate that Geuss could offer a number of reasons for finding Rawls′ conceptual innovations wanting. (shrink)

/strong>Almost all languages have included phonetics in language studies in some way. Arabic was one of the languages that had studied phonetics with more care. Phonetic studies are in general more likely to focus on qualitative articulation characteristics. Whereas either the need for an effort to produce a sound which implicit in articulation characteristics terms, or the ability of the vowels to be extended brings the relationship of sound and duration to the mind. In this work we are aiming, with (...) the help of terms that reflect the duration of articulation, to clarify the aspect of sound duration within disciplines concerned with speech sounds. From some terms used in tajwīd works especially within the section which hold the subject of preserving the scales of sounds and from other phenomena, we concluded that, at least in its practical goals, tajwīd works directed a balanced concern toward both the preservation of the quality and the quantity of speech sounds. (shrink)

Die Platonische Position des mengentheoretischen Universalismus, nach der das Mengenuniversum sprachunabhängig existiert, durch reine Anschauung erkannt und sprachlich mitteilbar ist, kann aus folgenden Gründen nicht aufrechterhalten werden: Die metalogischen Ergebnisse von Skolem und Löwenheim zeigen, daß die von einem Platonisten verwendete Sprache der engeren Quantorenlogik NichtStandard-Modelle besitzt, so daß er daher insbesondere nicht mitteilen kann, was er mit,Allklasse',,leere Klasse' und,Element' meint, da es nicht intendierte Interpretationen für diese Ausdrücke gibt. Hieraus folgt, daß der Zermelosche Mengentrichter, den der Platonist als durch (...) reine Anschauung zu erkennen vorgibt, auch im Sinne einer von ihm nicht intendierten Sprache der einfachen Typentheorie interpretierbar ist. Des weiteren gibt es weder die absolute Folge der Sprachstufen noch die dabei vorausgesetzten Ontologien. Diese Argumente stärken die Auffassung eines ontologischen Relativismus im Sinne von Gorgias. (shrink)

Zwei Philosophen, denen Kant am meisten zu verdanken hat, wie man mit dem Recht nimmt, sind Hume und Rousseau. W?hrend man?ber den Hume?s Einfluss einfach und eindeutig antworten kann, ist es mit dem Rousseau?s Einfluss viel mehr kompliziert. Der Haupteinfluss auf Kant hat Rousseau in der Ethik und auf der Ansicht der Menschen gemacht, deshalb es einen Anfangspunkt ist, durch welchem die Antwort auf diese Frage gesucht wird. Nach dieser Analyse wird eine einfache und eindeutige Antwort zu geben versucht, die?hnlich (...) wie diese, die man auf dem Hume?s Einfluss geben kann, ist: welchen Einfluss hat Rousseau auf dem ganzen Kritische System gemacht. Dva filozofa kojima Kant najvise duguje su, kako se obicno s pravom tvrdi, Hjum i Ruso. Dok se o Hjumovom uticaju moze jednoznacno i jednostavno odgovoriti, sa Rusoovim uticajem situacija je vidno komplikovanija. Osnovni uticaj na Kanta Ruso je imao u sferi etike i posmatranja coveka, tako da ce to biti polazna tacka preko koje ce se traziti odgovor na ovo pitanje, da bi se posle te analize pokusao dati jedan jednostavan i jednoznacan odgovor, slican onome koji se moze dati za Hjuma, o tome kakav uticaj je Ruso ostavio na celokupan sistem kriticke filozofije. (shrink)

Güzellik ve sanat iç içe geçmiş iki kavramdır. Bir bakıma güzellik, sanatın özüdür denilebilir. Her sanat dalında olduğu gibi hat sanatında da güzeli arama arzusu ve eşsiz eserler ortaya koyma çabası, hattatları sabırla çalışmaya ve kendi sınırlarını zorlamaya sevk etmiştir. Bir kitap sanatı olan hüsn-i hattın kelime manasının “güzel yazı” olmasına mukabil, daha iyisini yazmak uğruna harcanan çaba yorucu ve zahmetlidir, ancak sabırla çalışan elbette ki karşılığını alır. Başka bir deyişle “Muhakkak ki Allah güzeldir, güzeli sever!” hadis-i şerifi ışığında bu (...) sanata gönül verenler, yazıyı daha muntazam yazma hususunda büyük ölçüde gayret gösterirler. Kişinin muntazam yazmayı başarması ise, sistematik çalışmasına bağlıdır. Yazıyı kaidelerine uygun ve ölçülü yazabilmek bıkmadan usanmadan, karamsarlığa kapılmadan çalışmakla mümkündür. Bu sebeple gerek öğrenme aşamasında ve gerekse sonrasında, harfler defalarca çalışma kâğıdına yazılarak el melekesi artırılır. Kelimeler ve harfler kâğıda kimi zaman noktalanıp ölçülendirilerek, kimi zaman da noktalanmadan yazılır. Talim amaçlı yapılan bu çalışmalar, başka bir deyişle karalamalar, hat sanatının temeli niteliğindedir. Arap alfabesiyle yazılan ve “karalama” adı verilen el alıştırmaları yazıyla uğraşan kişinin o an irticalen elinden çıkan harf veya kelimelerden oluşur ve çoğu zaman bir anlam ifade etmez. Bu çalışmanın amacı, karalamaların estetik unsurlarını ele almak ve zaman içerisinde uğradığı değişime mercek tutmaktır. Hattatların bu özgür yorumları gün geçtikçe daha fazla önemsenmekte ve hayranlık uyandırmaktadır. Harf bünyesini oluşturan kaidelerin dışında satır ve sınırlara bağlı kalmadan yazılan bu yazılar kendi içinde bir kompozisyon oluşturmakta ve çoğu zaman yazan kişiyi dahi hayrete düşürecek özgün çalışmalar ortaya çıkabilmektedir. (shrink)

This article examines the relation between commercial activity and knowledge-making, looking at hatmakers in order to open up a more general question about the overlap between the knowledge practices of 19th-century science and those of everyday commercial culture of the time. Phrenology also claims attention here, since it can be said to have occupied an intermediate position between science and commerce. From time to time during the first half of the century, phrenologists attended to hatmakers in the hope of gleaning (...) knowledge from their commercial experience, but after about 1860, scientific craniometers took a very different view. Physical anthropologists like Paul Broca believed that the skull was the key source of data on which to build a scientific anthropology of race or ethnicity. Observers drew the attention of Broca and his colleagues to the existence of a commercial device called the conformateur des chapeliers, used by hatters to determine head shape. But Broca was far less inclined to welcome hatmakers into the domain of craniology than the phrenologists had been. Whereas phrenologists had found validation in common sense, any widely available understanding of racial types was considered by Broca to be a distraction from the work of science and a potential distortion of its data. Far from the welcoming curiosity shown by London-based phrenologists, the anthropological enterprise led by Broca defined itself as scientific in part by the strictness with which it considered and dismissed such approximate and informal ways of knowing. (shrink)

Prophets, Pre-Islamic; conduct of life; early works to 1800.

Emergence of the novel pathogenic coronavirus SARS‐CoV‐2 and its rapid pandemic spread presents challenges that demand immediate attention. Here, we describe the development of a semi‐quantitative high‐content microscopy‐based assay for detection of three major classes (IgG, IgA, and IgM) of SARS‐CoV‐2 specific antibodies in human samples. The possibility to detect antibodies against the entire viral proteome together with a robust semi‐automated image analysis workflow resulted in specific, sensitive and unbiased assay that complements the portfolio of SARS‐CoV‐2 serological assays. (...) Sensitive, specific and quantitative serological assays are urgently needed for a better understanding of humoral immune response against the virus as a basis for developing public health strategies to control viral spread. The procedure described here has been used for clinical studies and provides a general framework for the application of quantitative high‐throughput microscopy to rapidly develop serological assays for emerging virus infections. (shrink)

This article raises the question of whether there is one consistent theory of volitional acts in Husserl’s writings. The question arises because Husserl approaches volitional consciousness in his static and his genetic phenomenology rather differently. Static phenomenology understands acts of willing as complex, higher-order phenomena that are founded in both intellectual and emotional acts; while genetic phenomenology describes them as passively motivated phenomena that are implicitly predelineated in feelings, instincts, and drives, which always already include a characteristic element of striving. (...) Thus, according to genetic phenomenology, volitional acts are not founded on intellectual and emotional acts but rather influence those acts in their specific directedness. This article critically investigates four possible attempts to unite the two phenomenological approaches consistently and concludes that all these attempts are burdened with unsolved problems. It thus remains questionable whether Husserl has one consistent theory of volitional acts. (shrink)

To celebrate the acquisition of the Tom Phillips archive, the Bodleian Library has asked the artist to assemble and design a series of books drawing on his themed collection of over 50,000 photographic postcards. These encompass the first half of the twentieth century, a period in which, thanks to the ever cheaper medium of photography, ‘ordinary’ people could afford to own their portraits.Women in Hats explores the remarkable range in the world of millinery from outrageous Edwardian creations to the inventive (...) austerities of the Second World War.This book contains 200 images chosen with the eye of a leading artist from a visually rich vein of social history. Their covers will also feature a thematically linked painting, especially created for each title, from Tom Phillips’ signature work, A Humument. (shrink)

The principle of clinical equipoise requires that, aside from certain exceptional cases, second generation treatments ought to be tested against standard therapy. In violation of this principle, placebo-controlled trials (PCTs) continue to be used extensively in the development and licensure of second-generation treatments. This practice is typically justified by appeal to methodological arguments that purport to demonstrate that active-controlled trials (ACTs) are methodologically flawed. Foremost among these arguments is the so called assay sensitivity argument. In this paper, I take (...) a closer look at this argument. Following Duhem, I argue that all trials, placebo-controlled or not, rely on external information for their meaningful interpretation. Pending non-circular empirical evidence that we can trust the findings of PCTs to a greater degree than the findings of ACTs, I conclude that the assay sensitivity argument fails to demonstrate that placebo-controlled trials are preferable, methodologically or otherwise, to active-controlled trials. Contrary to the intentions of its authors, the fundamental lesson taught by the assay sensitivity argument is Duhemian: the validity of all clinical trials depends on external information. (shrink)

Die Platonische Position des mengentheoretischen Universalismus, nach der das Mengenuniversum sprachunabhängig existiert, durch reine Anschauung erkannt und sprachlich mitteilbar ist, kann aus folgenden Gründen nicht aufrechterhalten werden: Die metalogischen Ergebnisse von Skolem und Löwenheim zeigen, daß die von einem Platonisten verwendete Sprache der engeren Quantorenlogik NichtStandard-Modelle besitzt, so daß er daher insbesondere nicht mitteilen kann, was er mit,Allklasse',,leere Klasse' und,Element' meint, da es nicht intendierte Interpretationen für diese Ausdrücke gibt. Hieraus folgt, daß der Zermelosche Mengentrichter, den der Platonist als durch (...) reine Anschauung zu erkennen vorgibt, auch im Sinne einer von ihm nicht intendierten Sprache der einfachen Typentheorie interpretierbar ist. Des weiteren gibt es weder die absolute Folge der Sprachstufen noch die dabei vorausgesetzten Ontologien. Diese Argumente stärken die Auffassung eines ontologischen Relativismus im Sinne von Gorgias. (shrink)

Decision theory explicates norms of rationality for deriving preferences from preferences and beliefs. Empirical studies have found that actual preferences regularly violate these norms, launching a debate on whether this shows that subjects are prone to certain forms of irrationality or that decision theory needs to be revised. It has been claimed that such a revision is necessitated by the fact that normative uses of decision theory must be justified by a reflective equilibrium. The paper discusses three points. First, the (...) debate over the impact of empirical studies on decision theories is only meaningful with respect to a decision theory that includes not only a formal system but also a theory of application. Second, differences in the concepts of reflective equilibrium appealed to are a source of confusion in the debate on rationality. Third, the assumption that normative uses of decision theory are justified by reflective equilibrium is not sufficient ground for arguing that the empirical studies call for a revision of decision theory. Such an argument must rely on substantive claims about rationality, preferences and beliefs. (shrink)

A variety of relations widely invoked by philosophers—composition, constitution, realization, micro-basing, emergence, and many others—are species of what I call ‘building relations’. I argue that they are conceptually intertwined, articulate what it takes for a relation to count as a building relation, and argue that—contra appearances—it is an open possibility that these relations are all determinates of a common determinable, or even that there is really only one building relation.

Feminismus – das ist nicht nur für Männer, sondern auch für einige Frauen immer noch ein bedrohliches Wort, selbst oder gerade in Zeiten von #MeToo. Liegt das daran, dass viele gar nicht wissen, was Feminismus ist und worauf er hinarbeitet? Gibt es den einen Feminismus? Was hat Feminismus eigentlich mit Sexismus zu tun? Und was mit unseren Beziehungen? Die Philosophin Hilkje Hänel klärt über diese Fragen auf und plädiert für einen Feminismus, von dem alle etwas haben. Offener Frauenhass ist in (...) unserer Gesellschaft mittlerweile weitgehend geächtet. Aber auch nach über fünfzehn Jahren mit einer Frau an der Regierungsspitze sind wir noch längst nicht in der Gleichberechtigung angekommen. Im Gegenteil: Weiterhin strukturiert Sexismus geschlechtsspezifische Alltagserfahrungen, bis hinein in unsere Intimbeziehungen, wo die Grenzen zwischen Lust und sexueller Gewalt schnell verschwimmen. Die Philosophin und Schriftstellerin Hilkje Hänel deckt die Mechanismen sexueller Objektifizierung und männlichen Anspruchsdenkens auf. Sie zeigt, wie Frauen oft in die sexistischen Alltagsstrukturen verstrickt sind, an denen auch viele Männer leiden. Ihr zugängliches Buch ist das Plädoyer für einen Feminismus, von dem alle etwas haben. (shrink)

Husserl has undoubtedly considered himself being influenced by Brentano, but his conflicts with the orthodox core of the School of Brentano raise the question whether his adherence to Brentano suffices to adequately grasp the context of his early philosophy. I investigate the biographical details of Husserl’s studies in Vienna to uncover hitherto unknown ties between Husserl and Austrian philosophers outside the School of Brentano. Already during his secondary school studies in the Austro-Hungarian Monarchy Husserl was exposed to the philosophy textbooks (...) of Gustav Adolf Lindner; and archival records of the University of Vienna show that he had extensively attended philosophy courses held by other philosophers, especially by Robert Zimmermann. Both Lindner and Zimmermann proposed Herbartian philosophies, and what makes Zimmermann especially interesting is that he had once been a close personal disciple of Bernard Bolzano. I use an unpublished lecture transcript, written by a fellow student of Husserl, to investigate the controversial issue of Zimmermann’s possible transmission of Bolzano’s ideas. While a direct transmission seems improbable, my investigation uncovers a plethora of Herbartian influences, which are interesting on their own terms and have not only furnished Husserl with important parts of his descriptive psychological toolbox but have also helped him navigate the Brentano-School’s debate on intentionality. (shrink)