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)

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.

The link between broad based economic prosperity, political stability and accountable governance is generally acknowledged as a reasonable proposition to explain the wealth and poverty of nations. Although there is continuing debate about what accountable governance actually imply and the degree to which government accountability is related to the democratic nature of the state, there is a broad consensus that political stability is an important precondition for durable development. Modern Ethiopian history is nothing but a story of economic decline, political (...) instability and authoritarian governance. The TPLF/EPRDF regime that has taken power after overthrowing the hated Derge regime in Ethiopia has no democratic credentials especially since the 2005 election debacle. In the absence of democratic legitimacy, the government has hoped to ease public anger and frustration over the unfulfilled expectations of democracy and meaningful ethnic equality, by changing the discourse on governance from democratic accountability to the issue of economic growth. The regime's claim, which seems to be implicitly supported by Western donors, is that it is a "developmentalist state" that can deliver stable governance through its economic achievements rather than through democratic legitimacy. This paper looks at the government's claims carefully and shows that the economic growth figures used to support the government's claims are rather dubious. It also tries to show that even if the growth figures are true, the extent of poverty in the country is too high to generate durable political stability given the hostility the government created among key ethnic and social groups in the country. Furthermore, given the geo strategic location of the country in a very troubled region of the world, Ethiopia's instability is going to have a much broader implication for regional stability. Accordingly, the paper argues for refocusing the debate on democratic accountability in Ethiopia as a necessary condition for durable stability and sustainable development in the country and the larger region. (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)

/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)

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)

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 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)

One of the most difficult and interesting problems of rational decision is the choice among possible diverging paths in theory construction and among competing scientific theories—i.e., systems of accurate testable hypotheses. This task involves many beliefs—some warranted and others not as warranted—and marks decisive crossroads. Suffice to recall the current conflict between the general theory of relativity and alternative theories of gravitation that account for the same empirical evidence, the rivalry among different interpretations of quantum mechanics, and the variety of (...) cosmological theories. They all account for the same observed facts although they may predict different kinds of as yet unknown facts; they are consequently, up to now, empirically equivalent theories even though they are conceptually different and may even involve different philosophical views—i.e., they are conceptually inequivalent. (shrink)

This article suggests that institutional workshops of assay were significant experimental sites in early modern London. Master assayers at Goldsmiths’ Hall on Foster Lane, in the heart of the city, and at the Royal Mint, in the Tower, made trials to determine the precious-metal content of bullion, plate and coinage. The results of their metallurgical experiments directly impacted upon the reputations and livelihoods of London's goldsmiths and merchants, and the fineness of coin and bullion. Engaged in the separation and transformation (...) of matter, assayers and the affairs of their workshops were also a curiosity for those interested in the secrets of nature. Making use of a wide-ranging body of sources, including institutional court minutes, artisanal petitions, mercantile guidebooks, recipe books and natural-philosophical treatises, this article uncovers a complex culture of metropolitan expertise. We first examine the workshop spaces in which assayers undertook their professional activities, and their secretive corporate cultures. We turn next to the manuscript culture through which assayers codified and communicated knowledge, ‘secrets’ and techniques to broader urban audiences. Finally, we assess exchanges and tensions between assayers and the wider community of Londoners engaged in scientific knowledge production and dissemination. (shrink)

Immunology researchers are beginning to explore the possibilities of reproducibility, reuse and secondary analyses of immunology data. Open-access datasets are being applied in the validation of the methods used in the original studies, leveraging studies for meta-analysis, or generating new hypotheses. To promote these goals, the ImmPort data repository was created for the broader research community to explore the wide spectrum of clinical and basic research data and associated findings. The ImmPort ecosystem consists of four components–Private Data, Shared Data, Data (...) Analysis, and Resources—for data archiving, dissemination, analyses, and reuse. To date, more than 300 studies have been made freely available through the ImmPort Shared Data portal , which allows research data to be repurposed to accelerate the translation of new insights into discoveries. (shrink)

Microscale techniques have been applied to biological assays for nearly two decades, but haven't been widely integrated as common tools in biological laboratories. The significant differences between several physical phenomena at the microscale versus the macroscale have been exploited to provide a variety of new types of assays (such as gradient production or spatial cell patterning). However, the use of these devices by biologists seems to be limited by issues regarding biological validation, ease of use, and the limited available readouts (...) for assays done using microtechnology. Critical validation work has been done recently that highlights the current challenges for microfluidic methods and suggest ways in which future devices might be improved to better integrate with biological assays. With more validation and improved designs, microscale techniques hold immense promise as a platform to study aspects of cell biology that are not possible using current macroscale techniques. BioEssays 30:811–821, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

In the early twentieth century, viruses had yet to be defined in a material way. Instead, they were known better by what they were not – not bacteria, not culturable, and not visible with a light microscope. As with the ill-defined “gene” of genetics, viruses were microbes whose nature had not been revealed. Some clarity arrived in 1929 when Francis O. Holmes, a scientist at the Boyce Thompson Institute for Plant Research reported that Tobacco mosaic virus could produce local necrotic (...) lesions on tobacco plants and that these lesions were in proportion to dilutions of the inoculum. Holmes’ method, the local lesion assay, provided the first evidence that viruses were discrete infectious particles, thus setting the stage for physicochemical studies of plant viruses. In a field where there are few eponymous methods or diseases, Holmes’ assay continues to be a useful tool for the study of plant viruses. TMV was a success because the local lesion assay “made the virus visible” and standardized the work of virology towards determining the nature of the virus. (shrink)

A new split β‐lactamase assay promises experimental testing of the interplay of protein stability and function. Proteins are sufficiently stable to act effectively within cells. However, mutations generally destabilize structure, with effects on free energy that are comparable to the free energy of folding. Assays of protein functionality and stability in vivo enable a quick study of factors that influence these properties in response to targeted mutations. These assays can help molecular engineering but can also be used to target important (...) questions, including why most proteins are marginally stable, how mutations alter structural makeup, and how thermodynamics, function, and environment shape molecular change. Processes of self‐organization and natural selection are determinants of stability and function. Non‐equilibrium thermodynamics provides crucial concepts, e.g., cells as emergent energy‐dissipating entities that do work and build their own parts, and a framework to study the sculpting role of evolution at different scales. (shrink)

A new split β‐lactamase assay promises experimental testing of the interplay of protein stability and function. Proteins are sufficiently stable to act effectively within cells. However, mutations generally destabilize structure, with effects on free energy that are comparable to the free energy of folding. Assays of protein functionality and stability in vivo enable a quick study of factors that influence these properties in response to targeted mutations. These assays can help molecular engineering but can also be used to target important (...) questions, including why most proteins are marginally stable, how mutations alter structural makeup, and how thermodynamics, function, and environment shape molecular change. Processes of self‐organization and natural selection are determinants of stability and function. Non‐equilibrium thermodynamics provides crucial concepts, e.g., cells as emergent energy‐dissipating entities that do work and build their own parts, and a framework to study the sculpting role of evolution at different scales. (shrink)

The use of placebo in clinical trials has been repeatedly challenged as being unacceptable from an ethical point of view. The present paper responds to this criticism by taking up the issue in the light of the pertinent provisions of the Helsinki Declaration. Examples from different therapeutic areas are given that highlight the importance of placebo in situations in which its use is acceptable according to the Declaration. Particular emphasis is given to the question of active control trials, which, under (...) conditions of low assay sensitivity, may become an ethically less acceptable approach than the use of a placebo control. (shrink)

Multigene delivery and expression systems are emerging as key technologies for many applications in contemporary biology. We have developed new methods for multigene delivery and expression in eukaryotic hosts for a variety of applications, including production of protein complexes for structural biology and drug development, provision of multicomponent protein biologics, and cell‐based assays. We implemented tandem recombineering to facilitate rapid generation of multicomponent gene expression constructs for efficient transformation of mammalian cells, resulting in homogenous cell populations. Analysis of multiple parameters (...) in living cells may require co‐expression of fluorescently tagged sensors simultaneously in a single cell, at defined and ideally controlled ratios. Our method enables such applications by overcoming currently limiting challenges.Here, we review recent multigene delivery and expression strategies and their exploitation in mammalian cells. We discuss applications in drug discovery assays, interaction studies, and biologics production, which may benefit in the future from our novel approach. (shrink)

Intensive research and development of electrophoresis methodology and instrumentation during past decades has resulted in unique methods widely implemented in bioanalysis. While two‐dimensional electrophoresis and denaturing polyacrylamide gel electrophoresis in sodium dodecylsulfate are still the most frequently used electrophoretic methods applied to analyses of proteins, new miniaturized capillary and microfluidic versions of electromigrational methods have been developed. High‐throughput electrophoretic instruments with hundreds of capillaries for parallel separations and laser‐induced fluorescence detection of labeled DNA strands have been of key importance for (...) the scientific and commercial success of the Human Genome Project. Another powerful method, capillary isoelectric focusing with pressurized and pH‐driven mobilization, provides efficient separations and on‐line sensitive detection of proteins, bacteria and viruses. Electrophoretic microfluidic devices can integrate single‐cell injection, cell lysis, separation of its components and fluorescence or mass spectrometry detection. These miniaturized devices also proved the capability of single‐molecule detection. (shrink)

Medicejský dvorní filosof Galileo Galilei je považován za symbolického zakladatele vědecké metody oproštěné od vnějších vlivů, v níž rétorika, natož argumentační fauly, zdánlivě nemají své místo. Článek představuje pozadí vzniku a přijatých rétorických strategií málo zkoumaného spisu Il Saggiatore (Prubíř), jenž je zřejmě jedním z nejvýraznějších svědectví proti přetrvávajícímu černobílému obrazu Galilea jako nezávislého, výhradně racionálního vědce, jenž své myšlenky vyjadřuje jazykem matematiky a geometrie zproštěným emocí. Jak ale případ Prubíře zřetelně ukazuje, Galileo byl také dvořanem a literátem, jehož práce (...) byla silně ovlivňována přísnými pravidly patronátu. V reakci na knihu Libra astronomia ac philosophica jezuity Orazia Grassiho, jenž Galilea verbálně atakoval pod maskou fiktivního studenta jménem Lotario Sarsi, byl medicejský matematik přinucen bránit sebe a své patrony všemi dostupnými prostředky. Il Saggiatore však sloužil i k propagaci nových zásad vědeckého bádání zastávaných členy Accademia dei Linei. (shrink)

New Mechanist philosophical models of "phenomenon reconstitution" understand the process to be driven by explanatory considerations. Here I discuss an episode of phenomenon reconstitution that occurred entirely within an experimental program dedicated to characterizing the phenomenon of kinesin motility. Rather than being driven by explanatory considerations, as standard mechanist views maintain, I argue that the phenomenon of kinesin motility was reconstituted to enhance researchers’ primary experimental tool—the single molecule motility assay.

Sex- and age-specific rates of killing unrelated persons of one’s own sex were computed for Canada (1974–1983), England/Wales (1977–1986), Chicago (1965–1981), and Detroit (1972) from census information and data archives of all homicides known to police. Patterns in relation to sex and age were virtually identical among the four samples, although the rates varied enormously (from 3.7 per million citizens per annum in England/Wales to 216.3 in Detroit). Men’s marital status was related to the probability of committing a same-sex, nonrelative (...) homicide, but age effects remained conspicuous when married and unmarried men were distinguished.These findings and the treatment of age and sex effects by criminologists are discussed in the light of contemporary evolutionary psychological models of sex differences and life-span development. Same-sex homicides in which killer and victim are unrelated can be interpreted as an assay of competitive conflict. In every human society for which relevant information exists, men kill one another vastly more often than do women. Lethal interpersonal competition is especially prevalent among young men, which accords with many other aspects of life-span development in suggesting that sexual selection has maximized male competitive prowess and inclination in young adulthood. (shrink)

"Galileo on the Distinction between Primary and Secondary Qualities (I). A Superessentialist Argument" Galileo’s distinction between primary and secondary qualities has hitherto been examined almost exclusively from a contextual, historical perspective. This paper, the first of two planned, aims to fill this gap by providing a systematic, theoretical analysis of his principal argument for the distinction, as advanced in "The Assayer". I begin with a reconstruction of the key steps in the argument, and then proceed to identify and discuss the (...) epistemological and ontological presuppositions underpinning it. I argue that the most crucial and original assumption behind Galileo’s reasoning is the superessentialist principle, implying the mutual conditionality of the essentiality and reality of a material body’s properties. An in-depth analysis of the assumptions underlying Galileo’s reasoning paves the way for further examination of the most controversial aspect of his theory, that is, the ontological status of the secondary qualities. This issue will be addressed in the second forthcoming paper. (shrink)

Central to Watts and Newson’s argument in their seminal paper ‘ Is there a duty to routinely reinterpret genomic variant classifications? ’ is that diagnostic laboratories are not morally obligated to actively reinterpret variants of uncertain significance (VUS) due to the superior outcomes offered by next-generation sequencing (NGS) compared with traditional methods.1 NGS technologies can identify, analyse and interpret millions of genetic variations at once. For example, ‘the use of conventional molecular assays in clinical contexts could require doing a lot (...) of assays for various mutations. Using these different assays, more tissue may be required. These targets can accurately be questioned using NGS technology in a single test.’2 If NGS-based genomic sequencing is reliable and its output outweighs the potential harm of uncertainties, then, it is plausible to say that those test providers cannot incur a moral duty to actively reinterpret VUS because there won’t be any need to do so.1 Despite its seeming reliability, diagnostic laboratories face enormous challenges in implementing NGS-based …. (shrink)

Upon separation of the protein from the nucleic acid component of tobacco mosaic virus by phenol, using a fast and gentle procedure, the nucleic acid is infective in assays on tobacco leaves. A series of qualitative and quantitative control experiments demonstrates that the biological activity cannot depend on residual proteins in the preparation, but is a property of isolated nucleic acid which is thus the genetic material of the virus.