distinct property
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2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Shohei Beppu ◽  
Makoto Kinoshita ◽  
Jan Wilamowski ◽  
Tadahiro Suenaga ◽  
Yoshiaki Yasumizu ◽  
...  

AbstractNeuromyelitis optica spectrum disorder (NMOSD) is a relapsing autoimmune disease characterized by the presence of pathogenic autoantibodies, anti-aquaporin 4 (AQP4) antibodies. Recently, HLA-DQA1*05:03 was shown to be significantly associated with NMOSD in a Japanese patient cohort. However, the specific mechanism by which HLA-DQA1*05:03 is associated with the development of NMOSD has yet to be elucidated. In the current study, we revealed that HLA-DQA1*05:03 exhibited significantly higher cell surface expression levels compared to other various DQA1 alleles, and that its expression strongly depended on the amino acid sequence of the α1 domain, with a preference for leucine at position 75. Moreover, in silico analysis indicated that the HLA-DQ encoded by HLA-DQA1*05:03 preferentially presents immunodominant AQP4 peptides, and that the peptide major histocompatibility complexes (pMHCs) are more energetically stable in the presence of HLA-DQA1*05:03 than other HLA-DQA1 alleles. In silico 3D structural models were also applied to investigate the validity of the energetic stability of pMHCs. Taken together, our findings indicate that HLA-DQA1*05:03 possesses a distinct property to play a pathogenic role in the development of NMOSD.


2021 ◽  
pp. 1-45
Author(s):  
Anat Rosenberg

This article examines the role of law in shaping visual commercial culture by telling the story of the hoarding—the outdoor advertising surface for posters—in the formative decades of mass advertising in Britain, from roughly 1840 to 1914. The hoarding emerged in this period as a distinct property and a focal point of contestation over ways of seeing. Its meaning as a visual environment hinged on questions, which are still resonant today, about the interaction between economic and aesthetic categories: advertising and art, capital and beauty, commerce and culture. Historical actors—among them the organized billposting trade, the National Society for Checking the Abuses of Public Advertising, a civil society organization that took up the cause of protecting public spaces from advertising, governmental and local lawmakers, and citizens—enlisted private and public legal means to respond to these questions. This analysis draws on an expansive interdisciplinary archive to trace them. As it shows, legal means were engaged in cultural demarcation or what Thomas Gieryn has aptly termed boundary work. In establishing cultural boundaries, law defined the terms on which advertising became an integral element of daily visual experience, at once omnipresent and derided. The legal history of advertising thus offers deep insights for visual legal studies.


2021 ◽  
Author(s):  
Benjamin J Livesey ◽  
Joseph A Marsh

The assembly of proteins into complexes and interactions with other biomolecules are often vital for their biological function. While it is known that mutations at protein interfaces have a high potential to be damaging and cause human genetic disease, there has been relatively little consideration for how this varies between different types of interfaces. Here we investigate the properties of human pathogenic and putatively benign missense variants at homomeric (isologous and heterologous), heteromeric, DNA, RNA and other ligand interfaces, and at different regions with respect to those interfaces. We find that different types of interfaces vary greatly in their propensity to be associated with pathogenic mutations, with homomeric heterologous and DNA interfaces being particularly enriched in disease. We also find that residues that do not directly participate in an interface, but are close in 3D space, also show a significant disease enrichment. Finally, we show that mutations at different types of interfaces tend to have distinct property changes when undergoing amino acid substitutions associated with disease, and that this is linked to substantial variability in their identification by computational variant effect predictors.


2021 ◽  
pp. 194-244
Author(s):  
Ben McFarlane ◽  
Nicholas Hopkins ◽  
Sarah Nield

All books in this flagship series contain carefully selected substantial extracts from key cases, legislation, and academic debate, providing able students with a stand-alone resource. This chapter presents a discussion of licences. Licences can be grouped into a number of categories, including bare licences, contractual licences, estoppel licences, statutory licences, and licences coupled with an interest. The key feature of a bare licence is that A is under no duty to B not to revoke the licence. The distinction between a bare licence and a contractual licence turns on the question of whether A is under a contractual duty to B. An estoppel licence, as well as a statutory licence, is similar to a contractual licence: the key difference is the source of A’s duty to B. A ‘licence coupled with an interest’ is a permission to make a particular use of A’s land, which arises as part of a distinct property right held by B in A’s land. The chapter considers the impact of all these forms of licences, looking at the positions of A, of X (a stranger who interferes with the land), and of C (a party who acquires a right in the land from A). It considers whether particular forms of licence ought to count as equitable interests in land. It also examines when a licensee may be protected by a new, direct right against a third party, even though the licence itself is only a personal right.


2021 ◽  
Vol 17 (1) ◽  
pp. (A1)5-32
Author(s):  
Finlay Malcolm ◽  
Michael Scott
Keyword(s):  

Most contemporary accounts of the nature of faith explicitly defend what we call ‘the positivity theory of faith’ – the theory that faith must be accompanied by a favourable evaluative belief, or a desire towards the object of faith. This paper examines the different varieties of the positivity theory and the arguments used to support it. Whilst initially plausible, we find that the theory faces numerous problematic counterexamples, and show that weaker versions of the positivity theory are ultimately implausible. We discuss a distinct property of faith that we call ‘true grit’, such that faith requires one to be resilient toward the evidential, practical, and psychological challenges that it faces. We show how true grit is necessary for faith, and provides a simpler and less problematic explanation of the evidence used to support the positivity theory.


2020 ◽  
Author(s):  
Chenru Duan ◽  
Fang Liu ◽  
Aditya Nandy ◽  
Heather Kulik

Multireference (MR) diagnostics are common tools for identifying strongly correlated electronic structure that makes single reference (SR) methods (e.g., density functional theory or DFT) insufficient for accurate property prediction. However, MR diagnostics typically require computationally demanding correlated wavefunction theory (WFT) calculations, and diagnostics often disagree or fail to predict MR effects on properties. To overcome these challenges, we introduce a semi-supervised machine learning (ML) approach with virtual adversarial training (VAT) of an MR classifier using 15 WFT and DFT MR diagnostics as inputs. In semi-supervised learning, only the most extreme SR or MR points are labeled, and the remaining point labels are learned. The resulting VAT model outperforms the alternatives, as quantified by the distinct property distributions of SR- and MR-classified molecules. To reduce the cost of generating inputs to the VAT model, we leverage the VAT model’s robustness to noisy inputs by replacing WFT MR diagnostics with regression predictions in a MR decision engine workflow that preserves excellent performance. We demonstrate the transferability of our approach to larger molecules and those with distinct chemical composition from the training set. This MR decision engine demonstrates promise as a low-cost, high-accuracy approach to the automatic detection of strong correlation for predictive high-throughput screening.


2020 ◽  
Author(s):  
Chenru Duan ◽  
Fang Liu ◽  
Aditya Nandy ◽  
Heather Kulik

Multireference (MR) diagnostics are common tools for identifying strongly correlated electronic structure that makes single reference (SR) methods (e.g., density functional theory or DFT) insufficient for accurate property prediction. However, MR diagnostics typically require computationally demanding correlated wavefunction theory (WFT) calculations, and diagnostics often disagree or fail to predict MR effects on properties. To overcome these challenges, we introduce a semi-supervised machine learning (ML) approach with virtual adversarial training (VAT) of an MR classifier using 15 WFT and DFT MR diagnostics as inputs. In semi-supervised learning, only the most extreme SR or MR points are labeled, and the remaining point labels are learned. The resulting VAT model outperforms the alternatives, as quantified by the distinct property distributions of SR- and MR-classified molecules. To reduce the cost of generating inputs to the VAT model, we leverage the VAT model’s robustness to noisy inputs by replacing WFT MR diagnostics with regression predictions in a MR decision engine workflow that preserves excellent performance. We demonstrate the transferability of our approach to larger molecules and those with distinct chemical composition from the training set. This MR decision engine demonstrates promise as a low-cost, high-accuracy approach to the automatic detection of strong correlation for predictive high-throughput screening.


2020 ◽  
Vol 21 (13) ◽  
pp. 4602 ◽  
Author(s):  
Raj Kumar ◽  
Young Kyu Lee ◽  
Yong Seok Jho

Hyaluronic acid (HA) has a wide range of biomedical applications including the formation of hydrogels, microspheres, sponges, and films. The modeling of HA to understand its behavior and interaction with other biomolecules at the atomic level is of considerable interest. The atomistic representation of long HA polymers for the study of the macroscopic structural formation and its interactions with other polyelectrolytes is computationally demanding. To overcome this limitation, we developed a coarse grained (CG) model for HA adapting the Martini scheme. A very good agreement was observed between the CG model and all-atom simulations for both local (bonded interactions) and global properties (end-to-end distance, a radius of gyration, RMSD). Our CG model successfully demonstrated the formation of HA gel and its structural changes at high salt concentrations. We found that the main role of CaCl2 is screening the electrostatic repulsion between chains. HA gel did not collapse even at high CaCl2 concentrations, and the osmotic pressure decreased, which agrees well with the experimental results. This is a distinct property of HA from other proteins or polynucleic acids which ensures the validity of our CG model. Our HA CG model is compatible with other CG biomolecular models developed under the Martini scheme, which allows for large-scale simulations of various HA-based complex systems.


Author(s):  
Taro Kageyama

Due to the agglutinative character, Japanese and Ryukyuan morphology is predominantly concatenative, applying to garden-variety word formation processes such as compounding, prefixation, suffixation, and inflection, though nonconcatenative morphology like clipping, blending, and reduplication is also available and sometimes interacts with concatenative word formation. The formal simplicity of the principal morphological devices is counterbalanced by their complex interaction with syntax and semantics as well as by the intricate interactions of four lexical strata (native, Sino-Japanese, foreign, and mimetic) with particular morphological processes. A wealth of phenomena is adduced that pertain to central issues in theories of morphology, such as the demarcation between words and phrases; the feasibility of the lexical integrity principle; the controversy over lexicalism and syntacticism; the distinction of morpheme-based and word-based morphology; the effects of the stage-level vs. individual-level distinction on the applicability of morphological rules; the interface of morphology, syntax, and semantics, and pragmatics; and the role of conjugation and inflection in predicate agglutination. In particular, the formation of compound and complex verbs/adjectives takes place in both lexical and syntactic structures, and the compound and complex predicates thus formed are further followed in syntax by suffixal predicates representing grammatical categories like causative, passive, negation, and politeness as well as inflections of tense and mood to form a long chain of predicate complexes. In addition, an array of morphological objects—bound root, word, clitic, nonindependent word or fuzoku-go, and (for Japanese) word plus—participate productively in word formation. The close association of morphology and syntax in Japonic languages thus demonstrates that morphological processes are spread over lexical and syntactic structures, whereas words are equipped with the distinct property of morphological integrity, which distinguishes them from syntactic phrases.


2019 ◽  
Author(s):  
Arjun Byju ◽  
Deeti Patel ◽  
Weijie Chen ◽  
Sridhar Mani

AbstractA distinct property of many bacteria is swarming: swift movement across a surface through flagella propulsion. Early research indicates that bacterial swarming can be a protective host response to intestinal inflammation. Central to the further study of bacterial swarming in human health is an effective and replicable assay for swarming that can accommodate complex material, such as fecal matter. To date, nearly all swarming assays described in the literature are specific for bacteria grown in culture, most often Pseudomonas. In this paper, we describe a protocol for discerning swarming of bacteria from frozen human fecal samples. Moreover, we tested 4 variables that may influence the effectiveness of the assay: the method by which frozen samples were thawed, the concentration of agar used in the Lysogenic broth (LB) agar plate, the volume of LB agar poured in the plate, and the volume of sample inoculated. We found that while the type of thaw and volume of LB agar had little to no effect on swarming, greater concentrations of agar were negatively correlated with swarming and greater volumes of the sample were positively correlated with swarming.


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