Journal articles on the topic 'CUB model'
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1
Kopecký, Miloš, Jan Fábry, and Jiří Kub. "X-ray diffuse scattering in SrTiO3and model of atomic displacements." Journal of Applied Crystallography 45, no. 3 (April 25, 2012): 393–97. http://dx.doi.org/10.1107/s0021889812011867.
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The scattering intensity of synchrotron radiation in a compact three-dimensional volume of the reciprocal space (sinθmax/λ = 0.6283 Å−1) of an SrTiO3single crystal has been measured at temperatures of 115, 130 and 293 K. The curvilinear features of the diffuse pattern were modelled according to the displacements of both cations correlated along the axis [001]cub(where the subscript cub denotes the cubic structure). The results show that Sr2+is displaced from the ideal positions along the crystallographic axis [001]cub, forming a short chain composed of about three Sr2+ions along [001]cub, while the Ti4+ions are moved in the directions [111]cub, or alternatively [101]cubor [011]cub. The Ti4+displacements are also correlated along [001]cub, forming a similarly short chain.
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Cerulli, Giovanni, Rosaria Simone, Francesca Di Iorio, Domenico Piccolo, and Christopher F. Baum. "Fitting mixture models for feeling and uncertainty for rating data analysis." Stata Journal: Promoting communications on statistics and Stata 22, no. 1 (March 2022): 195–223. http://dx.doi.org/10.1177/1536867x221083927.
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In this article, we present the command cub, which fits ordinal rating data using combination of uniform and binomial (CUB) models, a class of finite mixture distributions accounting for both feeling and uncertainty of the response process. CUB identifies the components that define the mixture in the baseline model specification. We apply maximum likelihood methods to estimate feeling and uncertainty parameters, which are possibly explained in terms of covariates. An extension to inflated CUB models is discussed. We also present a subcommand, scattercub, for visualization of results. We then illustrate the use of cub using a case study on students’ satisfaction for the orientation services provided by the University of Naples Federico II in Italy.
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Montgomery, Robert B., Thian San Kheoh, Arturo Molina, Jinhui Li, Joaquim Bellmunt, Charles J. Ryan, Namphuong Tran, et al. "Effect of corticosteroid (CS) use at baseline (CUB) on overall survival (OS) in patients (pts) receiving abiraterone acetate (AA): Results from a randomized study (COU-AA-301) in metastatic castration-resistant prostate cancer (mCRPC) post-docetaxel (D)." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 5014. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.5014.
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5014 Background: CS have been used to mitigate mineralocorticoid-related effects and restore sensitivity to AA (Attard et al., J Clin Oncol. 2008). Prednisone (P) was also used as an active comparator in the COU-AA-301 (de Bono et al., N Engl J Med. 2011) and COU-AA-302 (Ryan et al., N Engl J Med. 2013) AA pivotal studies. CUB has also been reported to adversely influence OS in the AFFIRM study, which may reflect an influence on disease biology or unrecognized factors that are not a part of clinically based prognostic models (Scher et al., Ann Oncol. 2012). This post hoc exploratory analysis investigated whether CUB is a prognostic factor for OS in mCRPC post-D pts treated with AA + P or P alone. Methods: COU-AA-301 is a randomized double-blind study of AA (1 g) + P (5 mg po BID) vs placebo + P in mCRPC post-D. The primary endpoint was OS. All pts had received CS with D therapy. CUB included P (n = 272), dexamethasone (n = 107), and others (n = 110). 797 pts were not on CUB. Median times were estimated by the product-limit method; Cox model was used to obtain the hazard ratio (HR) and associated confidence interval (CI). Results: Pts with CUB had worse baseline disease characteristics (including adverse ECOG PS, Gleason score, analgesic score, and LDH) (all p < 0.05). Pts receiving CUB had inferior OS; AA + P improved OS independent of CUB. (Table). CUB was an independent prognostic factor in multivariate analysis (p = 0.03; HR 1.22 [95% CI: 1.02-1.45]) that was associated with lower baseline androgen levels (p < 0.0001). In a stepwise selection model, CUB was not an independent prognostic factor. Conclusions: In this study, CUB was not a strong independent prognostic factor in mCRPC post-D pts treated with AA + P or P alone. CUB was associated with worse baseline disease characteristics and inferior OS in this study, in which all pts subsequently received CS. Clinical trial information: NCT00638690. [Table: see text]
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Xue, Ying, Ran Li, Ping Fang, Zheng-qin Ye, Yong Zhao, Yun Zhou, Ke-qin Zhang, and Ling Li. "NLRP3 inflammasome inhibitor cucurbitacin B suppresses gout arthritis in mice." Journal of Molecular Endocrinology 67, no. 2 (August 1, 2021): 27–40. http://dx.doi.org/10.1530/jme-20-0305.
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Gouty arthritis is a common inflammatory disease characterized by monosodium urate (MSU) crystal-induced nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome activation with upregulated caspase 1 protease and IL-1β in macrophages. Cucurbitacin B (CuB) is a tetracyclic triterpene that possesses a potential anti-inflammatory activity. However, the immunomodulatory and anti-inflammatory effects of CuB on gout have not been well characterized. Therefore, the purpose of the present study was to determine whether CuB exhibits anti-inflammatory effects on gout and to analyze the underlying molecular mechanism. We examined the effects of CuB on various stimuli-activated bone marrow-derived macrophages (BMDMs) and in a mouse model with MSU-induced acute gouty arthritis. Our results demonstrated that CuB effectively suppressed multiple stimuli-activated IL-1β secretion by interrupting NLRP3 inflammasome complex formation, inhibiting NLRP3 inflammasome activation and suppressing key enzymes of glycolysis in macrophages. Consistent with this, CuB pretreatment also ameliorated MSU-induced arthritis in vivo models of gout arthritis, manifested by reduced foot swelling and inflammatory cell infiltration. Taken together, our data provide the evidence that CuB is an NLRP3 inflammasome inhibitor with therapeutic potential for treating NLRP3 inflammasome-mediated diseases, especially gouty arthritis.
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Lin, Yanfei, Yuki Kotakeyama, Jing Li, Yanjun Pan, Akira Matsuura, Yoshikazu Ohya, Minoru Yoshida, Lan Xiang, and Jianhua Qi. "Cucurbitacin B Exerts Antiaging Effects in Yeast by Regulating Autophagy and Oxidative Stress." Oxidative Medicine and Cellular Longevity 2019 (June 2, 2019): 1–15. http://dx.doi.org/10.1155/2019/4517091.
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The budding yeast Saccharomyces cerevisiae has been used as a model organism for the basic mechanism of aging, which provides useful assay systems for measuring both replicative and chronological lifespans. In the course of our screening program for substances that extend replicative lifespan, cucurbitacin B (CuB) was found as a hit compound from a compound library, which contains cerebrosides, phenols, sesquiterpenoid, triterpenoids, and sterols isolated from natural products by our research group. Importantly, it prolonged not only the replicative lifespan but also the chronological lifespan in yeast. CuB increased ATG32 gene expression, suggesting that CuB induces autophagy. Indeed, the GFP signal generated from the cleavage of GFP-Atg8, which is a signature of autophagy, was increased upon CuB treatment. On the other hand, CuB failed to increase the chronological lifespans when either ATG2 or ATG32, essential autophagy genes, was deleted, indicating that the lifespan extension by CuB depends on autophagy induction. Furthermore, CuB significantly increased superoxide dismutase (Sod) activity and the survival rate of yeast under oxidative stress, while it decreased the amount of reactive oxygen species (ROS) and malondialdehyde (MDA) production, indicating that CuB has activity to antagonize oxidative stress. Additionally, CuB did not affect replicative lifespans of sod1, sod2, uth1, and skn7 mutants with the K6001 background, indicating that aging-related genes including SOD1, SOD2, UTH1, and SKN7 participate in the antiaging effect of CuB. These results suggest that CuB exerts antiaging activity by regulating autophagy, ROS, antioxidative ability, and aging-related genes. Finally, we discuss the possible intracellular targets of CuB based on the phenotypic comparison between the CuB and global gene deletion databases.
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Liu, Pengfei, Yuchen Xiang, Xuewen Liu, Te Zhang, Rui Yang, Sen Chen, Li Xu, et al. "Cucurbitacin B Induces the Lysosomal Degradation of EGFR and Suppresses the CIP2A/PP2A/Akt Signaling Axis in Gefitinib-Resistant Non-Small Cell Lung Cancer." Molecules 24, no. 3 (February 12, 2019): 647. http://dx.doi.org/10.3390/molecules24030647.
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Non-small cell lung cancer (NSCLC) patients carrying an epidermal growth factor receptor (EGFR) mutation are initially sensitive to EGFR-tyrosine kinase inhibitors (TKIs) treatment, but soon develop an acquired resistance. The treatment effect of EGFR-TKIs-resistant NSCLC patients still faces challenges. Cucurbitacin B (CuB), a triterpene hydrocarbon compound isolated from plants of various families and genera, elicits anticancer effects in a variety of cancer types. However, whether CuB is a viable treatment option for gefitinib-resistant (GR) NSCLC remains unclear. Here, we investigated the anticancer effects and underlying mechanisms of CuB. We report that CuB inhibited the growth and invasion of GR NSCLC cells and induced apoptosis. The inhibitory effect of CuB occurred through its promotion of the lysosomal degradation of EGFR and the downregulation of the cancerous inhibitor of protein phosphatase 2A/protein phosphatase 2A/Akt (CIP2A/PP2A/Akt) signaling axis. CuB and cisplatin synergistically inhibited tumor growth. A xenograft tumor model indicated that CuB inhibited tumor growth in vivo. Immunohistochemistry results further demonstrated that CuB decreased EGFR and CIP2A levels in vivo. These findings suggested that CuB could suppress the growth and invasion of GR NSCLC cells by inducing the lysosomal degradation of EGFR and by downregulating the CIP2A/PP2A/Akt signaling axis. Thus, CuB may be a new drug candidate for the treatment of GR NSCLC.
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Barajas, Freddy Hernández, Olga Cecilia Usuga Manco, and Sebastián García Muñoz. "cubm package in R to fit CUB models." Comunicaciones en Estadística 11, no. 2 (December 21, 2018): 219–38. http://dx.doi.org/10.15332/2422474x.3857.
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The class of CUB models is commonly used by practitioners to model ordinal data, in this paper we propose the cubm package which provides the class of CUB models in the R system for statistical computing. The cubm package allows to specify a formula for each parameter of the model, the Maximum Likelihood (ML) estimation is performed by optimization via the functions nlminb, optim and DEoptim and the variance-covariance matrix can be obtained by numerical approximation of the Hessian matrix or by bootstrap method. The utility of the package is illustrated by an application and a simulation study.
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Seda, Ondrej, Frantisek Liska, Drahomira Krenova, Ludmila Kazdova, Lucie Sedova, Tomas Zima, Junzheng Peng, et al. "Dynamic genetic architecture of metabolic syndrome attributes in the rat." Physiological Genomics 21, no. 2 (April 14, 2005): 243–52. http://dx.doi.org/10.1152/physiolgenomics.00230.2004.
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The polydactylous rat strain (PD/Cub) is a highly inbred (F > 90) genetic model of metabolic syndrome. The aim of this study was to analyze the genetic architecture of the metabolic derangements found in the PD/Cub strain and to assess its dynamics in time and in response to diet and medication. We derived a PD/Cub × BN/Cub (Brown Norway) F2 intercross population of 149 male rats and performed metabolic profiling and genotyping and multiple levels of genetic linkage and statistical analyses at five different stages of ontogenesis and after high-sucrose diet feeding and dexamethasone administration challenges. The interval mapping analysis of 83 metabolic and morphometric traits revealed over 50 regions genomewide with significant or suggestive linkage to one or more of the traits in the segregating PD/Cub × BN/Cub population. The multiple interval mapping showed that, in addition to “single” quantitative train loci, there are more than 30 pairs of loci across the whole genome significantly influencing the variation of particular traits in an epistatic fashion. This study represents the first whole genome analysis of metabolic syndrome in the PD/Cub model and reveals several new loci previously not connected to the genetics of insulin resistance and dyslipidemia. In addition, it attempts to present the concept of “dynamic genetic architecture” of metabolic syndrome attributes, evidenced by shifts in the genetic determination of syndrome features during ontogenesis and during adaptation to the dietary and pharmacological influences.
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Garst, Barry A., Ryan J. Gagnon, Thomas Clanton, and Jay Woodward. "Cultivating Youth Affinity for College Within the Context of Campus-Based Summer Camps." Journal of Youth Development 16, no. 5 (December 14, 2021): 64–85. http://dx.doi.org/10.5195/jyd.2021.1083.
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College and university-based (CUB) summer camps are a prominent pre-collegiate experience targeting middle and high school adolescents, which research suggests may enhance college aspirations and preparedness, develop academic knowledge and skills, and influence future career choices. This study examines factors that predict the relation between affinity for college, program engagement and support, college major selection, and social–emotional outcomes stemming from youth involvement in a CUB camp based on data collected from 641 middle and high school-aged youth who completed an online questionnaire on the last day of the CUB camp. The findings validated a 4-factor model comprised of college brand awareness, college relational expectations, college academic interest–science, and college academic interest–technology. Further, the structural equation model (SEM) results suggested a relation between affinity for college, program engagement and support, and social–emotional outcomes. In addition, a CUB camp student’s lack of a college major had a significant negative direct effect on some dimensions of affinity for college including college brand awareness, college relational expectations, and college academic interest–science. CUB camp providers can use the results of this study to better articulate how their programs might impact adolescent decision making related to college, as well as inform how CUB camp providers may intentionally create affinity spaces that maximize student awareness of college brands as well as their future expectations for the college experience.
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Narenova, S. M., and A. S. Syzdykova. "THE EFFECTIVENESS OF USING THE DIDACTIC MODEL "CHEMICAL CUB" FOR TEACHING CHEMISTRY BY ENGLISH." Bulletin of Korkyt Ata Kyzylorda University 57, no. 2 (2021): 223–29. http://dx.doi.org/10.52081/bkaku.2021.v57.i2.059.
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мақалада авторлар әзірлеген «Химиялық текше-Chemical cub» дидактикалық үлгісін құрастырудың және химия пәнін ағылшын тілімен кіріктіріп оқыту процесінде қолданудың әдістемелік тәжірибесі келтірілген. «Химиялық текше-Chemical cub» дидактикалық үлгісінің сипаттамасы, орындалатын тапсырмалардың мысалдары мен химия сабақтарында және сабақтан тыс уақытта қолдану әдістемесі келтірілген. Бұл дидактикалық үлгі 2019-2020 және 2020-2021 оқу жылдарында Қызылорда қаласының мектерінде әдістемелік тәжиребеден өтті. Үлгі химия пәні мұғалімдеріне танысу үшін ұсынылды және мақалада сауалнама нәтижелері мен пән мұғалімдерінің пікірлері көрсетілген. «Химиялық текше-Chemical cub» дидактикалық үлгісін бейорганикалық химия курсының негізгі тақырыптарында, яғни 7-8 сыныптарда пайдаланудың әдістемесі қарастырылған. Дидактикалық үлгіні пайдалану арқылы білім алушылар тақырыптарды ағылшын тілінде оңай әрі қызықты меңгереді, ағылшын тілін негізгі 4 дағды (listening/тыңдалым, speaking/сөйлеу, reading/оқылым, writing/жазылым) бойынша меңгеруіне, сонымен қатар пәнге қызығушылығы артуына көмек бола алады. Мұғалім үшін CLIL технологиясы бойынша өтілген сабағының «пәндік мақсатына» да «тілдік мақсатына» да қол жеткізуге мүмкіндік береді. Әдістемелік тәжірибенің талдауы көрсеткендей, бұл дидактикалық үлгі оқу процесінде қолдану үшін тиімді және оқытудың әртүрлі формаларында қолдануға болады. Кілт сөздер: химиялық текше, кіріктірілу, әдістеме, дидактикалық модель, билингвалды, химияны оқыту
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Gautam, Avneesh Kumar, Yogesh Panse, Payel Ghosh, Malik Johid Reza, Jayati Mullick, and Arvind Sahu. "Mutational analysis of Kaposica reveals that bridging of MG2 and CUB domains of target protein is crucial for the cofactor activity of RCA proteins." Proceedings of the National Academy of Sciences 112, no. 41 (September 29, 2015): 12794–99. http://dx.doi.org/10.1073/pnas.1506449112.
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The complement system has evolved to annul pathogens, but its improper regulation is linked with diseases. Efficient regulation of the system is primarily provided by a family of proteins termed regulators of complement activation (RCA). The knowledge of precise structural determinants of RCA proteins critical for imparting the regulatory activities and the molecular events underlying the regulatory processes, nonetheless, is still limited. Here, we have dissected the structural requirements of RCA proteins that are crucial for one of their two regulatory activities, the cofactor activity (CFA), by using the Kaposi’s sarcoma-associated herpesvirus RCA homolog Kaposica as a model protein. We have scanned the entire Kaposica molecule by sequential mutagenesis using swapping and site-directed mutagenesis, which identified residues critical for its interaction with C3b and factor I. Mapping of these residues onto the modeled structure of C3b–Kaposica–factor I complex supported the mutagenesis data. Furthermore, the model suggested that the C3b-interacting residues bridge the CUB (complement C1r-C1s, Uegf, Bmp1) and MG2 (macroglobulin-2) domains of C3b. Thus, it seems that stabilization of the CUB domain with respect to the core of the C3b molecule is central for its CFA. Identification of CFA-critical regions in Kaposica guided experiments in which the equivalent regions of membrane cofactor protein were swapped into decay-accelerating factor. This strategy allowed CFA to be introduced into decay-accelerating factor, suggesting that viral and human regulators use a common mechanism for CFA.
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Liu, Bingchen, Kunpeng Song, Yizhe Zhu, Gerard De Melo, and Ahmed Elgammal. "TIME: Text and Image Mutual-Translation Adversarial Networks." Proceedings of the AAAI Conference on Artificial Intelligence 35, no. 3 (May 18, 2021): 2082–90. http://dx.doi.org/10.1609/aaai.v35i3.16305.
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Focusing on text-to-image (T2I) generation, we propose Text and Image Mutual-Translation Adversarial Networks (TIME), a lightweight but effective model that jointly learns a T2I generator G and an image captioning discriminator D under the Generative Adversarial Network framework. While previous methods tackle the T2I problem as a uni-directional task and use pre-trained language models to enforce the image--text consistency, TIME requires neither extra modules nor pre-training. We show that the performance of G can be boosted substantially by training it jointly with D as a language model. Specifically, we adopt Transformers to model the cross-modal connections between the image features and word embeddings, and design an annealing conditional hinge loss that dynamically balances the adversarial learning. In our experiments, TIME achieves state-of-the-art (SOTA) performance on the CUB dataset (Inception Score of 4.91 and Fréchet Inception Distance of 14.3 on CUB), and shows promising performance on MS-COCO dataset on image captioning and downstream vision-language tasks.
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Machado, Heather E., David S. Lawrie, and Dmitri A. Petrov. "Pervasive Strong Selection at the Level of Codon Usage Bias in Drosophila melanogaster." Genetics 214, no. 2 (December 23, 2019): 511–28. http://dx.doi.org/10.1534/genetics.119.302542.
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Codon usage bias (CUB), where certain codons are used more frequently than expected by chance, is a ubiquitous phenomenon and occurs across the tree of life. The dominant paradigm is that the proportion of preferred codons is set by weak selection. While experimental changes in codon usage have at times shown large phenotypic effects in contrast to this paradigm, genome-wide population genetic estimates have supported the weak selection model. Here we use deep genomic population sequencing of two Drosophila melanogaster populations to measure selection on synonymous sites in a way that allowed us to estimate the prevalence of both weak and strong purifying selection. We find that selection in favor of preferred codons ranges from weak (|Nes| ∼ 1) to strong (|Nes| > 10), with strong selection acting on 10–20% of synonymous sites in preferred codons. While previous studies indicated that selection at synonymous sites could be strong, this is the first study to detect and quantify strong selection specifically at the level of CUB. Further, we find that CUB-associated polymorphism accounts for the majority of strong selection on synonymous sites, with secondary contributions of splicing (selection on alternatively spliced genes, splice junctions, and spliceosome-bound sites) and transcription factor binding. Our findings support a new model of CUB and indicate that the functional importance of CUB, as well as synonymous sites in general, have been underestimated.
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Boatto, Vasco, Luca Rossetto, Paolo Bordignon, Rosa Arboretti, and Luigi Salmaso. "Cheese perception in the North American market." British Food Journal 118, no. 7 (July 4, 2016): 1747–68. http://dx.doi.org/10.1108/bfj-09-2015-0315.
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Purpose – The purpose of this paper is to detect market segments where consumers have a different knowledge of domestic and imported Parmesan cheese in USA and Canada. The results may be helpful in understanding to what extend North America consumers appreciate Parmesan cheese and brands, Parmesan consumption and price while recognizing market segments according to consumer awareness, involvement and covariate effects. Design/methodology/approach – A class of mixture models, known as combination uniform binomial (CUB), is applied to survey data collected in USA and Canada. A questionnaire, filled out by 540 restaurant customers, collects opinions about consumption, purchase features and price. The CUB model estimates the two latent variables, known as feeling and uncertainty, explaining the respondent’s behavior as awareness and involvement variability while the CUB clustering procedure detects market segments. Findings – CUB results show that the Parmesan is a well-known cheese but also that a small share of consumers look for the place of origin. The model detects market segments where consumers express better awareness on taste, price and origin while the knowledge of imported Parmesan brands is lacking. Most of consumers, not paying attention to the origin, would hardly switch to the imported Parmesan because of higher price or because they are already satisfied of the domestic cheese. Research limitations/implications – The results suffer some restrictions in the sample representativeness. A further analysis, where the survey is done at retail and advances in CUB models, may improve the market segmentation procedure allowing a better generalization of results. Practical implications – The survey results highlights the appreciation and consumption of Parmesan cheese, especially for its taste, as well as a low perception of Italian brands. Consequently, trade companies should focussed their communication strategy on activities encouraging North American consumers to taste Italian Parmesan brands (e.g. tasting sessions, price promotions) instead of costly and less effective advertising campaigns. Social implications – Parmesan brand misunderstandings are often associated with market information asymmetry. The paper results show a market segmentation where purchases are mainly driven by Parmesan taste regardless of domestic or imported brands. Likely, the consumption of domestic Parmesan is well consolidated and it is not a consequence of brand information asymmetry. Originality/value – The CUB model is an innovative and flexible no parametric approach for evaluating consumer behavior and for segmenting the market while dealing with complex problems of food knowledge.
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Kurman, Yener, Ilker Kiliccioglu, Asiye U. Dikmen, Guldal Esendagli, Cenk Y. Bilen, Sinan Sozen, and Ece Konac. "Cucurbitacin B and cisplatin induce the cell death pathways in MB49 mouse bladder cancer model." Experimental Biology and Medicine 245, no. 9 (April 6, 2020): 805–14. http://dx.doi.org/10.1177/1535370220917367.
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Cisplatin-based chemotherapy is the standard regimen for bladder cancer patients, but its effectiveness is limited by high toxicity and the development of drug resistance. It has been reported in many studies that Cucurbitacin B has anti-carcinogenic effects by stimulating apoptosis and autophagy. Here we explored the potential role of cucurbitacin B on MB49 bladder syngeneic mouse tumor model. Single and combined doses of cucurbitacin B and cisplatin were applied to MB49 cell line and the cell viability was determined by Water‐Soluble Tetrazolium Salt‐1 (WST) method. After developing the tumor model, mice were randomly divided into four groups and then cucurbitacin B and cisplatin applied in the specified doses and time. The expression levels of apoptosis (Bcl-2, Bax, Caspase-3, cleaved Caspase-3) and autophagy proteins (Beclin-1 and LC3I, LC3II) were detected by Western Blot. Phospho-protein array analysis was performed to determine the relative levels of phosphorylation of proteins which are associated with the PI3K-Akt signaling pathway. Tumor tissues were analyzed by hematoxylin-eosin staining. In the present study, the results showed that cucurbitacin B inhibited the expression of Bcl-2 and increased the expression of Bax and cleaved Caspase 3. LC3II is markedly up-regulated in cucurbitacin B-treated cells. Cucurbitacin B reduced the phosphorylation of p27, PRAS40, and Raf-1 proteins. CuB + Cis combination synergistically decreased phosphorylation of AKT, ERK1/ERK2, mTOR, BAD levels and increased the level of AMPKα. PI3K/AKT/ mTOR pathway might be one of the targets of cucurbitacin B in MB49 bladder cancer mouse model. CuB + Cis combination reduced the tumor growth. Cucurbitacin B has no toxic effects on lung, liver, kidney, heart, and bladder. Indeed, cucurbitacin B can inhibit the tumor proliferation; induce caspase-dependent/-independent apoptosis and autophagy. Our study provided a novel perspective to research the effects of cucurbitacin B on the apoptotic and autophagic pathways in bladder cancer and a new target class for drug development. Impact statement Alternative agents that will increase the effectiveness of cisplatin, which are widely used in the advanced stage and metastatic bladder cancer, are being investigated. In previous studies, Cucurbitacin B (CuB), which is a natural compound from the Cucurbitaceae family has been shown to inhibit the proliferation of tumor cells and create synergistic effects with cisplatin. In this study, we investigated the synergistic effect of CuB with cisplatin for the first time in bladder cancer in vitro and in vivo models. Our findings showed that CuB treatment with cisplatin reduced cell proliferation, and reduced tumor development through activating apoptosis and autophagy via PI3K/AKT/mTOR signaling pathway. Our results showed that CuB may be a new agent that can support conventional treatment in bladder cancer. Our study is important in terms of enlightening new pathways and developing new treatment methods in the treatment of bladder cancer.
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Mason, Maria G., Peter Nicholls, and Chris E. Cooper. "The steady-state mechanism of cytochrome c oxidase: redox interactions between metal centres." Biochemical Journal 422, no. 2 (August 13, 2009): 237–46. http://dx.doi.org/10.1042/bj20082220.
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The steady-state behaviour of isolated mammalian cytochrome c oxidase was examined by increasing the rate of reduction of cytochrome c. Under these conditions the enzyme's 605 (haem a), 655 (haem a3/CuB) and 830 (CuA) nm spectral features behaved as if they were at near equilibrium with cytochrome c (550 nm). This has implications for non-invasive tissue measurements using visible (550, 605 and 655 nm) and near-IR (830 nm) light. The oxidized species represented by the 655 nm band is bleached by the presence of oxygen intermediates P and F (where P is characterized by an absorbance spectrum at 607 nm relative to the oxidized enzyme and F is characterized by an absorbance spectrum at 580 nm relative to the oxidized enzyme) or by reduction of haem a3 or CuB. However, at these ambient oxygen levels (far above the enzyme Km), the populations of reduced haem a3 and the oxygen intermediates were very low (<10%). We therefore interpret 655 nm changes as reduction of the otherwise spectrally invisible CuB centre. We present a model where small anti-cooperative redox interactions occur between haem a–CuA–CuB (steady-state potential ranges: CuA, 212–258 mV; haem a, 254–281 mV; CuB, 227–272 mV). Contrary to static equilibrium measurements, in the catalytic steady state there are no high potential redox centres (>300 mV). We find that the overall reaction is correctly described by the classical model in which the Michaelis intermediate is a ferrocytochrome c–enzyme complex. However, the oxidation of ferrocytochrome c in this complex is not the sole rate-determining step. Turnover is instead dependent upon electron transfer from haem a to haem a3, but the haem a potential closely matches cytochrome c at all times.
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Pratama, Jaka Aulia, Zulhanif Zulhanif, and Yadi Suprijadi. "KLASIFIKASI KARAKTERISTIK KONSUMEN SEPEDA MOTOR MERK T DI JAWA BARAT MENGGUNAKAN METODE NAÏVE BAYES CLASSIFIER PADA DATA MINING." Jurnal Ilmiah Matematika dan Pendidikan Matematika 9, no. 2 (December 29, 2017): 37. http://dx.doi.org/10.20884/1.jmp.2017.9.2.2864.
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PT. JKL has a role as a main dealer of T’s brand are handling three types of motorcycle products in West Java. These are type of Sport, CUB, and Scooter(Automatic Transmissions). The company records the buyer of T’s brand motorcycle in the Customer Database (CDB). CDB collected from 2011 to 2013 yielded information of consumer characteristics which is necessary in market planning. Consumer characteristics are classified into two groups: Repeated Order and New Customer. Classification methods used in the study of Data Mining is the Naïve Bayes Classifier. Model classification is done by calculating the conditional probability to choose the greatest value of probability. The accuracy of the classification is 83% and the error classification is 17%.
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Reyes Rojas, Luis A., Italo Moletto-Lobos, Fabio Corradini, Cristian Mattar, Rodrigo Fuster, and Cristián Escobar-Avaria. "Determining Actual Evapotranspiration Based on Machine Learning and Sinusoidal Approaches Applied to Thermal High-Resolution Remote Sensing Imagery in a Semi-Arid Ecosystem." Remote Sensing 13, no. 20 (October 13, 2021): 4105. http://dx.doi.org/10.3390/rs13204105.
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Evapotranspiration (ET) is key to assess crop water balance and optimize water-use efficiency. To attain sustainability in cropping systems, especially in semi-arid ecosystems, it is necessary to improve methodologies of ET estimation. A method to predict ET is by using land surface temperature (LST) from remote sensing data and applying the Operational Simplified Surface Energy Balance Model (SSEBop). However, to date, LST information from Landsat-8 Thermal Infrared Sensor (TIRS) has a coarser resolution (100 m) and longer revisit time than Sentinel-2, which does not have a thermal infrared sensor, which compromises its use in ET models as SSEBop. Therefore, in the present study we set out to use Sentinel-2 data at a higher spatial-temporal resolution (10 m) to predict ET. Three models were trained using TIRS’ images as training data (100 m) and later used to predict LST at 10 m in the western section of the Copiapó Valley (Chile). The models were built on cubist (Cub) and random forest (RF) algorithms, and a sinusoidal model (Sin). The predicted LSTs were compared with three meteorological stations located in olives, vineyards, and pomegranate orchards. RMSE values for the prediction of LST at 10 m were 7.09 K, 3.91 K, and 3.4 K in Cub, RF, and Sin, respectively. ET estimation from LST in spatial-temporal relation showed that RF was the best overall performance (R2 = 0.710) when contrasted with Landsat, followed by the Sin model (R2 = 0.707). Nonetheless, the Sin model had the lowest RMSE (0.45 mm d−1) and showed the best performance at predicting orchards’ ET. In our discussion, we argue that a simplistic sinusoidal model built on NDVI presents advantages over RF and Cub, which are constrained to the spatial relation of predictors at different study areas. Our study shows how it is possible to downscale Landsat-8 TIRS’ images from 100 m to 10 m to predict ET.
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Reyes Rojas, Luis A., Italo Moletto-Lobos, Fabio Corradini, Cristian Mattar, Rodrigo Fuster, and Cristián Escobar-Avaria. "Determining Actual Evapotranspiration Based on Machine Learning and Sinusoidal Approaches Applied to Thermal High-Resolution Remote Sensing Imagery in a Semi-Arid Ecosystem." Remote Sensing 13, no. 20 (October 13, 2021): 4105. http://dx.doi.org/10.3390/rs13204105.
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Evapotranspiration (ET) is key to assess crop water balance and optimize water-use efficiency. To attain sustainability in cropping systems, especially in semi-arid ecosystems, it is necessary to improve methodologies of ET estimation. A method to predict ET is by using land surface temperature (LST) from remote sensing data and applying the Operational Simplified Surface Energy Balance Model (SSEBop). However, to date, LST information from Landsat-8 Thermal Infrared Sensor (TIRS) has a coarser resolution (100 m) and longer revisit time than Sentinel-2, which does not have a thermal infrared sensor, which compromises its use in ET models as SSEBop. Therefore, in the present study we set out to use Sentinel-2 data at a higher spatial-temporal resolution (10 m) to predict ET. Three models were trained using TIRS’ images as training data (100 m) and later used to predict LST at 10 m in the western section of the Copiapó Valley (Chile). The models were built on cubist (Cub) and random forest (RF) algorithms, and a sinusoidal model (Sin). The predicted LSTs were compared with three meteorological stations located in olives, vineyards, and pomegranate orchards. RMSE values for the prediction of LST at 10 m were 7.09 K, 3.91 K, and 3.4 K in Cub, RF, and Sin, respectively. ET estimation from LST in spatial-temporal relation showed that RF was the best overall performance (R2 = 0.710) when contrasted with Landsat, followed by the Sin model (R2 = 0.707). Nonetheless, the Sin model had the lowest RMSE (0.45 mm d−1) and showed the best performance at predicting orchards’ ET. In our discussion, we argue that a simplistic sinusoidal model built on NDVI presents advantages over RF and Cub, which are constrained to the spatial relation of predictors at different study areas. Our study shows how it is possible to downscale Landsat-8 TIRS’ images from 100 m to 10 m to predict ET.
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Mazumder, Pratik, Pravendra Singh, and Piyush Rai. "Few-Shot Lifelong Learning." Proceedings of the AAAI Conference on Artificial Intelligence 35, no. 3 (May 18, 2021): 2337–45. http://dx.doi.org/10.1609/aaai.v35i3.16334.
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Many real-world classification problems often have classes with very few labeled training samples. Moreover, all possible classes may not be initially available for training, and may be given incrementally. Deep learning models need to deal with this two-fold problem in order to perform well in real-life situations. In this paper, we propose a novel Few-Shot Lifelong Learning (FSLL) method that enables deep learning models to perform lifelong/continual learning on few-shot data. Our method selects very few parameters from the model for training every new set of classes instead of training the full model. This helps in preventing overfitting. We choose the few parameters from the model in such a way that only the currently unimportant parameters get selected. By keeping the important parameters in the model intact, our approach minimizes catastrophic forgetting. Furthermore, we minimize the cosine similarity between the new and the old class prototypes in order to maximize their separation, thereby improving the classification performance. We also show that integrating our method with self-supervision improves the model performance significantly. We experimentally show that our method significantly outperforms existing methods on the miniImageNet, CIFAR-100, and CUB-200 datasets. Specifically, we outperform the state-of-the-art method by an absolute margin of 19.27% for the CUB dataset.
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Костенко, М. Г., and А. А. Ремпель. "Распределение вакансий в гибридной сверхструктуре M-=SUB=-(5-11/18)-=/SUB=-X-=SUB=-(5-11/18)-=/SUB=- высокотемпературной упорядоченной фазы beta-TiO." Физика твердого тела 60, no. 3 (2018): 456. http://dx.doi.org/10.21883/ftt.2018.03.45544.254.
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AbstractA new structural model of the high-temperature ordered β-TiO phase of titanium monoxide with vacancies in metallic and nonmetallic sublattices has been proposed. The model suggests that the vacancies are simultaneously distributed over sites of two partially disordered superstructures: monoclinic M_5X_5(mon) (space group C 2/ m ( A 2/ m )) and cubic M_5X_5(cub) (space group Pm $$\overline 3 $$ 3 ¯ m ). The hybrid superstructure belongs to space group P 1 m 1 of the monoclinic system. The proposed notation M_(5–11/18)X_(5–11/18) of the hybrid superstructure takes into account an expansion of the vacancy sublattice due to the superposition of initial $${M_5}{X_{{5^ - }}}$$ M 5 X 5 − type superstructures. It is shown that the arrangements of the superstructure reflections in the diffraction spectra of the M_(5–11/18)X_(5–11/18) and M_5X_5(cub) superstructures are identical.
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Popovic, Dragan, and Ivana Djordjevic. "Catalytic center of cytochrome c oxidase: Effects of protein environment on pKa values of cub histidine ligands." Journal of the Serbian Chemical Society 85, no. 11 (2020): 1429–44. http://dx.doi.org/10.2298/jsc200720047p.
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The molecular mechanism by which electron transfer (ET) is coupled to proton pumping in cytochrome oxidase is one of the main unsolved problems in biochemistry. Particularly, the nature and position of the proton-loading site is under dispute. The CuB complex has three ligated histidines, whereas only His290 and His291 are ionizable sites with the same pKa values in aqueous solution, but apparently quite different ones within the enzyme. Earlier, a model of proton pumping with the central role of His290 was proposed. Recent calculations indicate that the His291 ligand of the CuB center might play the role of the pumping element, since its protonation state depends on the oxidation state of the binuclear complex (BNC). The present electrostatic study was applied to assess the role of the protein environment on the acidity of the two histidines. Their pKa values and effects of different energy terms were evaluated to discover the nature of their diverse behavior in the enzyme. Here, a new set of pKa values for the non-standard model compounds within the BNC was applied. The enhanced results are compared with results of previous studies in the light of the plausible proton pumping mechanism. The obtained microscopic and apparent pKa values in the oxidized state of BNC are virtually the same, indicating that deprotonated form of His291 accounts for the large pKa increase of His290, since then both titratable sites on then CuB center cannot simultaneously be in the charged state. The present results support the underlined His291 pumping model.
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Leute, Volkmar, S. Brinkmann, J. Linnenbrink, and H. M. Schmidtke. "The Phase Diagram of the Quasiternary System (Sn, Pb) (S,Te)." Zeitschrift für Naturforschung A 50, no. 4-5 (May 1, 1995): 459–67. http://dx.doi.org/10.1515/zna-1995-4-520.
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Abstract The phase diagram of the quasiternary system (Snt Pb1-k)(S,Te1-l) for 900 K is determined by X-ray diffraction and by electron microprobe analysis. Moreover, the free enthalpy faces g(k, I) for the phases with cubic rocksalt structure (cub) or with the orthorhombic SnS structure (orh) are calculated from the interaction parameters and from the orh → cub transition data of the 4 quasibinary subsystems. The interaction parameters are also used to calculate the termodynamic factor for interdiffusion along quasibinary sections through the phase square and to calculate the energies of four-particle clusters. By application of the cluster model one obtains information on the local environment of the mixing particles and on the cluster processes that have effect upon interdiffusion
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Ferrini, Paola, Claudio Chesi, Nicholas Parkin, and Roberto Rinaldi. "Effect of methanol in controlling defunctionalization of the propyl side chain of phenolics from catalytic upstream biorefining." Faraday Discussions 202 (2017): 403–13. http://dx.doi.org/10.1039/c7fd00069c.
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In recent years, lignin valorization has gained upward momentum owing to advances in both plant bioengineering and catalytic processing of lignin. In this new horizon, catalysis is now applied to the ‘pulping process’ itself, creating efficient methods for lignocellulose fractionation or deconstruction (here referred to as Catalytic Upstream Biorefining or ‘CUB’). These processes render, together with delignified pulps, lignin streams of low molecular weight (Mw) and low molecular diversity. Recently, we introduced a CUB process based on Early-stage Catalytic Conversion of Lignin (ECCL) through H-transfer reactions catalyzed by RANEY® Ni. This approach renders a lignin stream obtained as a viscous oil, comprising up to 60 wt% monophenolic compounds (Mw < 250 Da). The remaining oil fraction (40 wt%) is mainly composed of lignin oligomers, and as minor products, holocellulose-derived polyols and lignin-derived species of high Mw (0.25–2 kDa). Simultaneously, the process yields a holocellulose pulp with a low content of residual lignin (<5 wt%). Despite the efficiency of aqueous solutions of 2-propanol as a solvent for lignin fragments and an H-donor, there is scant information regarding the CUB process carried out in the presence of primary alcohols, which often inhibit the catalytic activity of RANEY® Ni, as revealed in model compound studies performed at low temperature. Considering the composition of the lignin oils obtained from CUB based on ECCL, the processes commonly render ortho-(di)methoxy-4-propylphenol derivatives with a varied degree of defunctionalization of the propyl side chain. In this contribution, we present the role of the alcohol solvent (methanol or 2-propanol) and Ni catalyst (Ni/C or RANEY® Ni) in control over selectivity of phenolic products. The current results indicate that solvent effects on the catalytic processes could hold the key for improving control over the degree of functionalization of the propyl side-chain in the lignin oil obtained from CUB, offering new avenues for lignin valorization at the extraction step.
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Bansal, Shilpi, Mallana Gowdra Mallikarjuna, Alexander Balamurugan, S. Chandra Nayaka, and Ganesan Prakash. "Composition and Codon Usage Pattern Results in Divergence of the Zinc Binuclear Cluster (Zn(II)2Cys6) Sequences Among Ascomycetes Plant Pathogenic Fungi." Journal of Fungi 8, no. 11 (October 27, 2022): 1134. http://dx.doi.org/10.3390/jof8111134.
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Zinc binuclear cluster proteins (ZBC; Zn(II)2Cys6) are unique to the fungi kingdom and associated with a series of functions, viz., the utilization of macromolecules, stress tolerance, and most importantly, host–pathogen interactions by imparting virulence to the pathogen. Codon usage bias (CUB) is the phenomenon of using synonymous codons in a non-uniform fashion during the translation event, which has arisen because of interactions among evolutionary forces. The Zn(II)2Cys6 coding sequences from nine Ascomycetes plant pathogenic species and model system yeast were analysed for compositional and codon usage bias patterns. The clustering analysis diverged the Ascomycetes fungi into two clusters. The nucleotide compositional and relative synonymous codon usage (RSCU) analysis indicated GC biasness toward Ascomycetes fungi compared with the model system S. cerevisiae, which tends to be AT-rich. Further, plant pathogenic Ascomycetes fungi belonging to cluster-2 showed a higher number of GC-rich high-frequency codons than cluster-1 and was exclusively AT-rich in S. cerevisiae. The current investigation also showed the mutual effect of the two evolutionary forces, viz. natural selection and compositional constraints, on the CUB of Zn(II)2Cys6 genes. The perseverance of GC-rich codons of Zn(II)2Cys6 in Ascomycetes could facilitate the invasion process. The findings of the current investigation show the role of CUB and nucleotide composition in the evolutionary divergence of Ascomycetes plant pathogens and paves the way to target specific codons and sequences to modulate host–pathogen interactions through genome editing and functional genomics tools
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Lamonaca, Emilia, Barbara Cafarelli, Crescenza Calculli, and Caterina Tricase. "Consumer perception of attributes of organic food in Italy: A CUB model study." Heliyon 8, no. 3 (March 2022): e09007. http://dx.doi.org/10.1016/j.heliyon.2022.e09007.
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Carpita, Maurizio, Enrico Ciavolino, and Mariangela Nitti. "The MIMIC–CUB Model for the Prediction of the Economic Public Opinions in Europe." Social Indicators Research 146, no. 1-2 (March 24, 2018): 287–305. http://dx.doi.org/10.1007/s11205-018-1885-4.
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Ervitasari, Aning, and Ade Iriani. "Evaluation of the Scout Extracurricular Program to Improve the Character of Elementary School Students." Indonesian Values and Character Education Journal 5, no. 2 (December 12, 2022): 52–60. http://dx.doi.org/10.23887/ivcej.v5i2.51808.
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The low character possessed by students causes a decline in ethics and morals among students. So efforts are needed to be able to improve the character possessed by students. The purpose of this study was to evaluate the achievement of the goals of the cub scout extracurricular program. This research is a qualitative descriptive study, and its evaluation uses the goal-free evaluation model. The research subjects were school principals, cub masters, scout trainers, and 58 extracurricular participants. Observations, interviews, and documentation studies are the data collection techniques used in this study. Data analysis techniques were carried out in four stages, starting from 1) data collection, 2) data reduction, 3) data presentation, and 4) conclusion. The data validity in this study used technique and source triangulation. The results showed that the scout extracurricular improved students' character because character education was implemented in the content. Still, the purpose of the scout extracurricular program had not been achieved 100%. So it is hoped that these extracurricular activities will be carried out more intensively to have a positive impact, especially in shaping and developing student character.
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Cope, Alexander L., and Premal Shah. "Intragenomic variation in non-adaptive nucleotide biases causes underestimation of selection on synonymous codon usage." PLOS Genetics 18, no. 6 (June 17, 2022): e1010256. http://dx.doi.org/10.1371/journal.pgen.1010256.
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Patterns of non-uniform usage of synonymous codons vary across genes in an organism and between species across all domains of life. This codon usage bias (CUB) is due to a combination of non-adaptive (e.g. mutation biases) and adaptive (e.g. natural selection for translation efficiency/accuracy) evolutionary forces. Most models quantify the effects of mutation bias and selection on CUB assuming uniform mutational and other non-adaptive forces across the genome. However, non-adaptive nucleotide biases can vary within a genome due to processes such as biased gene conversion (BGC), potentially obfuscating signals of selection on codon usage. Moreover, genome-wide estimates of non-adaptive nucleotide biases are lacking for non-model organisms. We combine an unsupervised learning method with a population genetics model of synonymous coding sequence evolution to assess the impact of intragenomic variation in non-adaptive nucleotide bias on quantification of natural selection on synonymous codon usage across 49 Saccharomycotina yeasts. We find that in the absence of a priori information, unsupervised learning can be used to identify genes evolving under different non-adaptive nucleotide biases. We find that the impact of intragenomic variation in non-adaptive nucleotide bias varies widely, even among closely-related species. We show that the overall strength and direction of translational selection can be underestimated by failing to account for intragenomic variation in non-adaptive nucleotide biases. Interestingly, genes falling into clusters identified by machine learning are also physically clustered across chromosomes. Our results indicate the need for more nuanced models of sequence evolution that systematically incorporate the effects of variable non-adaptive nucleotide biases on codon frequencies.
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Nagano, Yasutomo, Jin-Gang Liu, Yoshinori Naruta, and Teizo Kitagawa. "UV resonance Raman study of model complexes of the CuB site of cytochrome c oxidase." Journal of Molecular Structure 735-736 (February 2005): 279–91. http://dx.doi.org/10.1016/j.molstruc.2004.11.012.
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Panda, Siva Prasad, Asit Kumar Sarangi, and Uttam Prasad Panigrahy. "ISOLATION OF CUCURBITACIN-B FROM CUCUMIS CALLOSUS AND ITS HYPOGLYCEMIC EFFECT IN ISOLATED RAT ENTEROCYTES." International Journal of Pharmacy and Pharmaceutical Sciences 10, no. 5 (May 1, 2018): 123. http://dx.doi.org/10.22159/ijpps.2018v10i5.25788.
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Objective: The pericarp of fruits of Cucumis callous (Rottl.) Cogn. (Cucurbitaceae) is traditionally used for curing diabetes, epilepsy, and diarrhea. It has an active compound include Cucurbitacin-B (CuB), which acts as a potent inducer of CYP450 of rat enterocytes. This study was conducted with the aim of elaborating and reconciling our previous finding on the glucose-lowering effect of Cucumis callosus (Rottl.) Cogn. fruits.Methods: In vivo hypoglycemic potential for methanolic pericarp extracts from C callosus (MPCC, 350 mg/kg b.w. p. o), methanolic seed extract of C callosus (MSCC, 250 mg/kg b.w. p. o) and CuB (80 µg/kg b.w. p. o) were studied in streptozotocin (STZ, 55 mg/kg b.w. i. p) induced diabetic rats. Metformin (25 mg/kg b.w. p. o) served as reference drug. Ex vivo model of intestinal tissue preparation of Swiss albino rats named Single Pass Intestinal Perfusion (SPIP) technique was performed for ex vivo hypoglycemic study. The glucose levels in the serosal fluid were determined by commercially available glucose oxidase kit and compared with the standard drug metformin (0.1 mg/kg).Results: In vivo results showed that administration of MPCC (350 mg/kg b.w. p. o) and Cucurbitacin-B (80 µg/kg b.w. p. o) produced the hypoglycemic effect. The MPCC (1.4 mg/kg) and CuB (0.4 µg/kg) produced hypoglycemic effect in ex vivo technique. These effects are due to induction of 0.53 mµmoles of CYP450 proteins with maximum absorption at 454 mµ in rat enterocytes.Conclusion: The present investigation gave evidence that bitter pericarp of C callosus fruit has a hypoglycemic effect due to the presence of Cucurbitacin B as phytoconstituent but seeds did not have such effects.
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Li, Zhiheng, Tongcheng Gu, Bing Li, Wubin Xu, Xin He, and Xiangyu Hui. "ConvNeXt-Based Fine-Grained Image Classification and Bilinear Attention Mechanism Model." Applied Sciences 12, no. 18 (September 8, 2022): 9016. http://dx.doi.org/10.3390/app12189016.
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Thus far, few studies have been conducted on fine-grained classification tasks for the latest convolutional neural network ConvNeXt, and no effective optimization method has been made available. To achieve more accurate fine-grained classification, this paper proposes two attention embedding methods based on ConvNeXt network and designs a new bilinear CBAM; simultaneously, a multiscale, multi-perspective and all-around attention framework is proposed, which is then applied in ConvNeXt. Experimental verification shows that the accuracy rate of the improved ConvNeXt for fine-grained image classification reaches 87.8%, 91.2%, and 93.2% on fine-grained classification datasets CUB-200-2011, Stanford Cars, and FGVC Aircraft, respectively, showing increases of 2.7%, 0.3% and 0.4%, respectively, compared to those of the original network without optimization, and increases of 3.7%, 8.0% and 2.0%, respectively, compared to those of the traditional BCNN. In addition, ablation experiments are set up to verify the effectiveness of the proposed attention framework.
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Guo, Jing-Ming, Sankarasrinivasan Seshathiri, and Wen-Hsiang Chen. "Few-Shot Classification with Dual-Model Deep Feature Extraction and Similarity Measurement." Electronics 11, no. 21 (October 28, 2022): 3502. http://dx.doi.org/10.3390/electronics11213502.
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From traditional machine learning to the latest deep learning classifiers, most models require a large amount of labeled data to perform optimal training and obtain the best performance. Yet, when limited training samples are available or when accompanied by noisy labels, severe degradation in accuracy can arise. The proposed work mainly focusses on these practical issues. Herein, standard datasets, i.e., Mini-ImageNet, CIFAR-FS, and CUB 200, are considered, which also have similar issues. The main goal is to utilize a few labeled data in the training stage, extracting image features and then performing feature similarity analysis across all samples. The highlighted aspects of the proposed method are as follows. (1) The main self-supervised learning strategies and augmentation techniques are exploited to obtain the best pretrained model. (2) An improved dual-model mechanism is proposed to train the support and query datasets with multiple training configurations. As examined in the experiments, the dual-model approach obtains superior performance of few-shot classification compared with all of the state-of-the-art methods.
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Hidayat, Sunarto, Haris Abizar, and Sulaeman Deni Ramdani. "Media Pembelajaran Cutting Engine Sistem Transmisi Sepeda Motor Manual Tipe CUB." Jurnal Pendidikan Teknik Mesin 8, no. 2 (November 25, 2021): 140–50. http://dx.doi.org/10.36706/jptm.v8i2.15567.
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This paper reports a study that examines the manufacture and feasibility of cutting engine learning media. learning in related subjects. The research was conducted using the Research and Development (R&D) method of the Borg and Gall development model. The subjects of this study consisted of 3 material experts, 3 media experts, and 21 college students. This research produces Learning Media products that have a choice of operating modes (automatic or mechanical) as well as visualization transfer features that make this product a flexible character learning medium. The feasibility of learning media based on the validation results from material experts and media experts shows that this learning media is suitable for use in learning. The average result of the questionnaire that has been obtained from media experts shows a percentage of 78% in the "Good" category. The average results of media experts show a percentage of 86.60% in the "Very Good" category and the average for the questionnaire that has been obtained from users shows a percentage of 87.20% in the "Very Good" category.
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Capecchi, Stefania, Isabella Endrizzi, Flavia Gasperi, and Domenico Piccolo. "A multi-product approach for detecting subjects’ and objects’ covariates in consumer preferences." British Food Journal 118, no. 3 (March 7, 2016): 515–26. http://dx.doi.org/10.1108/bfj-10-2015-0343.
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Purpose – A different framework based on a parametric version of the process generating the hedonic scores is adopted. More precisely, a probability distribution for ordinal responses is proposed as a mixture of two components, denoted as feeling (as expressed preference) and uncertainty component (as inherent indecision). The purpose of this paper is to analyse the effect of covariates on the consumers’ behaviour pattern according to a statistical model. Design/methodology/approach – Sample data come from a multidisciplinary research aimed to improve the quality and marketability of soft fruits. Then, a stochastic model with subjects’ and objects’ covariates is built and the interpretation of significant results is discussed. Findings – The joint effects of personal characteristics and chemical contents of juice on the hedonic scores given by consumers are examined and graphically depicted by means of a significant model. Originality/value – The paper suggests a multi-product approach to expressed hedonic scores by means of a generalization of CUB models.
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He, Jingyuan, and Bailong Yang. "Fine-grained Image Recognition Method using Discriminative Region-based Data Augmentation." Frontiers in Computing and Intelligent Systems 1, no. 3 (October 17, 2022): 8–12. http://dx.doi.org/10.54097/fcis.v1i3.1973.
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In order to reduce the complexity of the network model and improve the accuracy of image recognition, a fine-grained image recognition method using discriminative region-based data augmentation is proposed. The method obtains the discriminative regions of the image through the attention mechanism, and then performs diversity data augmentation based on the discriminative regions, including region crop, region drop and region mix, and then uses the generated augmented samples to train the network model, the backbone network of the model is ResNet50. The proposed method is tested on 4 commonly used fine-grained image datasets CUB-200-2011, Stanford Cars, FGVC Aircraft and Stanford Dogs, and achieves high accuracy. The experimental results show that the proposed method can improve the localization ability and feature extraction ability of the model for discriminative regions, and it is more lightweight and easier to implement.
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Dai, Xinghua, Shengrong Gong, Shan Zhong, and Zongming Bao. "Bilinear CNN Model for Fine-Grained Classification Based on Subcategory-Similarity Measurement." Applied Sciences 9, no. 2 (January 16, 2019): 301. http://dx.doi.org/10.3390/app9020301.
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One of the challenges in fine-grained classification is that subcategories with significant similarity are hard to be distinguished due to the equal treatment of all subcategories in existing algorithms. In order to solve this problem, a fine-grained image classification method by combining a bilinear convolutional neural network (B-CNN) and the measurement of subcategory similarities is proposed. Firstly, an improved weakly supervised localization method is designed to obtain the bounding box of the main object, which allows the model to eliminate the influence of background noise and obtain more accurate features. Then, sample features in the training set are computed by B-CNN so that the fuzzing similarity matrix for measuring interclass similarities can be obtained. To further improve classification accuracy, the loss function is designed by weighting triplet loss and softmax loss. Extensive experiments implemented on two benchmarks datasets, Stanford Cars-196 and Caltech-UCSD Birds-200-2011 (CUB-200-2011), show that the newly proposed method outperforms in accuracy several state-of-the-art weakly supervised classification models.
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Saquil, Yassir, Qun-Ce Xu, Yong-Liang Yang, and Peter Hall. "Rank3DGAN: Semantic Mesh Generation Using Relative Attributes." Proceedings of the AAAI Conference on Artificial Intelligence 34, no. 04 (April 3, 2020): 5586–94. http://dx.doi.org/10.1609/aaai.v34i04.6011.
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In this paper, we investigate a novel problem of using generative adversarial networks in the task of 3D shape generation according to semantic attributes. Recent works map 3D shapes into 2D parameter domain, which enables training Generative Adversarial Networks (GANs) for 3D shape generation task. We extend these architectures to the conditional setting, where we generate 3D shapes with respect to subjective attributes defined by the user. Given pairwise comparisons of 3D shapes, our model performs two tasks: it learns a generative model with a controlled latent space, and a ranking function for the 3D shapes based on their multi-chart representation in 2D. The capability of the model is demonstrated with experiments on HumanShape, Basel Face Model and reconstructed 3D CUB datasets. We also present various applications that benefit from our model, such as multi-attribute exploration, mesh editing, and mesh attribute transfer.
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Nagano, Y., T. Kitagawa, Jin-Gang L., and Y. Naruta. "1P120 UV resonance Raman study of a model complex of the CuB site of cytochrome c oxidase." Seibutsu Butsuri 44, supplement (2004): S59. http://dx.doi.org/10.2142/biophys.44.s59_4.
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Siva, Amara C., Martha A. Wild, Richard E. Kirkland, Mary Jean Nolan, Bing Lin, Toshiaki Maruyama, Ferda Yantiri-Wernimont, Shana Frederickson, Katherine S. Bowdish, and Hong Xin. "Targeting CUB Domain-Containing Protein 1 with a Monoclonal Antibody Inhibits Metastasis in a Prostate Cancer Model." Cancer Research 68, no. 10 (May 15, 2008): 3759–66. http://dx.doi.org/10.1158/0008-5472.can-07-1657.
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Schelpe, An-Sofie, Anastasis Petri, Nele Vandeputte, Hans Deckmyn, Simon F. De Meyer, James TB Crawley, and Karen Vanhoorelbeke. "Anti-CUB1 or Anti-Spacer Antibodies That Increase ADAMTS13 Activity Act By Allosterically Enhancing Metalloprotease Domain Function." Blood 132, Supplement 1 (November 29, 2018): 23. http://dx.doi.org/10.1182/blood-2018-99-117061.
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Abstract Background ADAMTS13 circulates in a folded conformation, which is mediated by interactions between the C-terminal CUB domains and its central Spacer domain. Binding of ADAMTS13 to the VWF D4-CK domains disrupts the CUB-Spacer interaction, inducing a structural change that extends ADAMTS13 into an open conformation that enhances catalytic efficiency ~2-fold. This mechanism supports a model in which ADAMTS13 unfolding induces exposure of an exosite in the Spacer domain that interacts with the VWF A2 domain, increasing the affinity between the two molecules, and, therefore, the rate of proteolysis. The D4-CK-mediated conformational activation of ADAMTS13 can be mimicked in vitro with the use of antibodies that disrupt the CUB-Spacer interaction, such as the previously published anti-CUB antibody, Ab17G2. We recently generated a novel, activating antibody against the Spacer domain (Ab3E4). Aim To characterize the mechanism by which the Ab17G2 and Ab3E4 enhance the catalytic efficiency of ADAMTS13. Methods The effects of the Ab17G2 and Ab3E4 on the activity of ADAMTS13 were studied using FRETS-VWF73. The effects of the Ab17G2 and Ab3E4 on the kinetics of VWF96 (VWF G1573-R1668) proteolysis were characterized using an in-house assay. ELISA was used to investigate conformational changes in ADAMTS13 induced by the Ab17G2 and Ab3E4. Results Both Ab17G2 and Ab3E4 enhanced FRETS-VWF73 proteolysis by ~1.7-fold. This result was reproduced using the VWF96 substrate; the Ab17G2 and Ab3E4 enhanced the catalytic efficiency (kcat/Km) of ADAMTS13 by ~1.8- and ~2.0-fold, respectively. The activation was dependent on the conformational extension of ADAMTS13, since the antibodies could not enhance the activity of an ADAMTS13 variant that lacks the TSP2-CUB2 domains (MDTCS). Surprisingly, ADAMTS13 activation was not mediated through exposure of the Spacer or Cys-rich domain exosites as previously proposed, as the Ab17G2 and Ab3E4 efficiently enhanced proteolysis of VWF96 variants in which the Spacer/Cys-rich exosite binding sites were disrupted. Kinetic analysis of VWF96 proteolysis showed that the Ab17G2- and Ab3E4-induced activation of ADAMTS13 is primarily manifest through a ~1.5- to ~2-fold increase in enzyme turnover (kcat). Thus, contrary to the current model, this suggests that the conformational extension of ADAMTS13 influences the functionality of the active site, and not substrate binding affinity (Km). Incubating ADAMTS13 with either Ab17G2 or Ab3E4 exposed a cryptic epitope in the metalloprotease domain that was specifically detected by ELISA, further corroborating that the antibodies induce a conformational change in ADAMTS13 affecting the M domain. Conclusion Antibodies can be used as tools for understanding the structure/function of enzymes. Using activating antibodies against the Spacer and CUB1 domains of ADAMTS13, we show for the first time that the activation of ADAMTS13 following its unfolding is not a result of exposure of a functional exosite in Spacer/Cys-rich domain that increases affinity to VWF. Rather, our data are consistent with an allosteric activation mechanism upon the metalloprotease domain. We propose that ADAMTS13 unfolding causes a conformational change in the active site that further activates the enzyme. We are currently investigating whether the D4-CK-induced enhancement of ADAMTS13 proteolytic activity is also mediated by conformational changes in the active site. Disclosures Vanhoorelbeke: Ablynx: Consultancy; Shire: Consultancy.
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Hristienko, Hank, Douglas Pastuck, Ken J. Rebizant, Brian Knudsen, and M. Laurene Connor. "Using reproductive data to model American black bear cub orphaning in Manitoba due to spring harvest of females." Ursus 15, no. 1 (April 2004): 23–34. http://dx.doi.org/10.2192/1537-6176(2004)015<0023:urdtma>2.0.co;2.
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Zhu, Jian, Joshua Muia, Niraj H. Tolia, Lisa A. Westfield, and J. Evan Sadler. "A Folded ADAMTS13 Conformation Identified By Small-Angle X-Ray Scattering Can Account for Allosteric Regulation By Distal Thrombospondin-1 and CUB Domains." Blood 124, no. 21 (December 6, 2014): 107. http://dx.doi.org/10.1182/blood.v124.21.107.107.
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Abstract Introduction: ADAMTS13 is a multidomain protein with metalloprotease (M), disintegrin-like (D), thrombospondin-1 (T), Cys-rich (C) and spacer (S) domains, followed by 7 T domains and 2 CUB domains. ADAMTS13 cleaves the cryptic Tyr1605-Met1606 bond in the A2 domain of von Willerbrand factor (VWF), which inhibits the growth of platelet-rich thrombi. When subjected to tensile stress in solution, bound to platelets, or on endothelial cell surfaces, VWF interacts with multiple exosites on ADAMTS13, changing the conformation of both proteins. These close contacts enhance the highly specific interaction between ADAMTS13 and VWF in vivo. Interactions between VWF and proximal MDTCS domains of ADAMTS13 have been investigated extensively. ADAMTS13 distal domains T8-CUB2 are required to bind the D4 domain of VWF, and the CUB domains promote the cleavage of platelet-decorated VWF strings. However, the functional relationship between distal and proximal domains is not understood. Using mutagenesis, small-angle X-ray scattering (SAXS) and enzyme kinetics, we now have shown that distal T8-CUB domains interact with and inhibit the proximal MDTCS domains. Methods: Recombinant ADAMTS13, MDTCS, and variants truncated after each distal T domain (MT2, MT3ÉMT8), and VWF D4 domain were produced in T-Rex 293 cell lines and purified to homogeneity. Similar inactive variants of each protein were prepared with the mutation E225Q, which abolishes catalytic activity but does not affect protein folding (MT2Q, MT3QÉMT8Q). SAXS data were collected at the SIBYLS beamline (Lawrence Berkeley National Laboratory) for ADAMTS13 (E225Q) and truncated variants. The radius of gyration (Rg) and maximum particle size (Dmax) were calculated from scattering profiles using DATGNOM. Ab initio envelopes were generated from scattering profiles using DAMMIN. A molecular model of ADAMTS13 was built from crystal structures of ADAMTS4 MD domains (2rjp) and ADAMTS13 DTCS domains (3ghm), and using HHpred to model distal T domains, CUB domains, and linkers after T4 and T8. Plasma VWF was purified from Facteur Willebrand-LFB concentrate on Superdex 200. ADAMTS13 activity assays were performed at pH 6 and pH 7.4 with fluorogenic substrate FRETS-rVWF71. Results: Rg and Dmax progressively increased for variants MDTCS, MT2, MT3, MT4 and MT5, but did not increase proportionately for MT7, MT8 and ADAMTS13 despite a 50% increase in mass (Table 1). This behavior is consistent with a folded conformation. Fitting ADAMTS13 into ab initio envelopes for these variants requires a bend after domain T4, which is followed by a flexible linker that could serve as a hinge. As a consequence, distal T8-CUB2 domains are positioned near the proximal MDTCS domains (Figure 1). At pH 7.4, variants MDTCS through MT7 had similar activity toward FRETS-rVWF71. Full length ADAMTS13 was only ~10% as active at pH 7.4, but was ~7-fold more active at pH 6. MT8 had intermediate activity at pH 7.4 and was not activated by lowering the pH to 6. Adding VWF or recombinant VWF D4 increased the cleavage of FRETS-rVWF71 by full-length ADAMTS13 up to 4-fold at pH 7.4, but had no effect at pH 6 and did not change the activity of MT8 or MDTCS. Conclusions: ADAMTS13 adopts a folded conformation with distal T8-CUB2 domains close to the proximal MDTCS domains and a hinge point between the T4 and T5 domains. The T8-CUB domains inhibit ADAMTS13 activity, and this autoinhibition can be relieved by low pH or by binding to VWF. Thus, VWF functionally serves as both an ADAMTS13 activator and substrate. This allosteric mechanism would localize and concentrate ADAMTS13 activity on VWF multimers at sites of thrombosis. Table 1 Properties of ADAMTS13 Variants Variant Mass (kDa) Rg(Angstrom)a Dmax(Angstrom)b kcat, pH 6 (min-1)c kcat, pH 7.4 (min-1)c MDTCS 67 45.2 ± 1.1 148.3 ± 2.0 9.86 ± 0.04 10.94 ± 0.01 MT2 73 47.8 ± 2.8 154.8 ± 6.1 9.19 ± 0.24 10.23 ± 0.07 MT3 79 54.3 ± 4.8 179.5 ± 10.1 9.69 ± 0.27 9.69 ± 0.27 MT4 90 58.7 ± 3.7 193.1 ± 15.9 7.85 ± 0.04 9.80 ± 0.27 MT5 96 63.4 ± 3.0 210.1 ± 8.9 7.23 ± 0.23 9.43 ± 0.22 MT7 109 63.8 ± 2.0 210.5 ± 11.5 8.34 ± 0.25 8.90 ± 0.10 MT8 121 64.7 ± 2.5 206.2 ± 2.5 3.01 ± 0.02 2.44 ± 0.01 ADAMTS13 147 67.2 ± 1.9 228.9 ± 6.2 7.15 ± 0.20 1.05 ± 0.11 aCalculated using the program AutoRg, errors are SD. bCalculated using the program DATGNOM, errors are SD. cErrors are SE Figure 1 Ab Initio Models of ADAMTS13 Variants Figure 1. Ab Initio Models of ADAMTS13 Variants Disclosures Sadler: XO1 Limited: Membership on an entity's Board of Directors or advisory committees; BioMarin: Consultancy; Band Therapeutics: Consultancy; Baxter HealthCare: Consultancy, Honoraria.
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Vorontsova, Elena L., and Sergey A. Khlyupin. "Orangutan Phryne. First year in Moscow." Moscow University Anthropology Bulletin (Vestnik Moskovskogo Universiteta. Seria XXIII. Antropologia), no. 2 (July 14, 2022): 130–39. http://dx.doi.org/10.32521/2074-8132.2022.2.130-139.
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Introduction. The life of a female orangutan named "Phryne" is described in the article. Phryne lived in the Moscow Zoo in 1927–1936. Large apes can serve as model objects for studying the processes of human growth and development, the formation of mental qualities and social hierarchy, as well as ecological relationships. Therefore, the preservation of accumulated experience is an extremely important task. Materials and methods. Materials from scientific and popular publications, as well as archival materials are used in this work. Analytical and chronological research methods were used. Results. Male and female orangutans were captured on the island of Sumatra in 1926 for the Moscow Zoo. In April 1927, during transportation, the female gave birth to a cub. The apes arrived at the Moscow Zoo on July 14. The female was seriously ill. On July 27 she died. The cub was left without a mother. M.A. Velichkovsky, the head of the monkey section, fed the baby with goat's milk from a pacifier. The baby was first mistaken for a male and named Fritz. After a few years, people realized that it was a female. She was named Phryne. The article talks about Phryne's childhood, about the attitude of the male towards her, about the nutrition of monkeys. It also addresses the fate of the head of the monkey section M.A. Velichkovsky. Conclusion. The first year of Phryne's life was very difficult. The experience of growing an orangutan has become an important stage in the development of the Moscow Zoo.
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Yang, Yadong, Xiaofeng Wang, and Hengzheng Zhang. "Local Importance Representation Convolutional Neural Network for Fine-Grained Image Classification." Symmetry 10, no. 10 (October 11, 2018): 479. http://dx.doi.org/10.3390/sym10100479.
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Compared with ordinary image classification tasks, fine-grained image classification is closer to real-life scenes. Its key point is how to find the local areas with sufficient discrimination and perform effective feature learning. Based on a bilinear convolutional neural network (B-CNN), this paper designs a local importance representation convolutional neural network (LIR-CNN) model, which can be divided into three parts. Firstly, the super-pixel segmentation convolution method is used for the input layer of the model. It allows the model to receive images of different sizes and fully considers the complex geometric deformation of the images. Then, we replaced the standard convolution of B-CNN with the proposed local importance representation convolution. It can score each local area of the image using learning to distinguish their importance. Finally, channelwise convolution is proposed and it plays an important role in balancing lightweight network and classification accuracy. Experimental results on the benchmark datasets (e.g., CUB-200-2011, FGVC-Aircraft, and Stanford Cars) showed that the LIR-CNN model had good performance in fine-grained image classification tasks.
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Wilson, Ann, and Clive J. C. Phillips. "Identification and Evaluation of African Lion (Panthera leo) Cub Welfare in Wildlife-Interaction Tourism." Animals 11, no. 9 (September 20, 2021): 2748. http://dx.doi.org/10.3390/ani11092748.
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African lion (Panthera leo) cubs are extensively used in South Africa in wildlife-interaction tourist activities. Facilities provide close interaction opportunities, but the welfare impacts on the cubs are unclear. A workshop was held with 15 lion-experienced stakeholders, including government officials, nature conservationists, animal welfare organisations, lion breeders, lion handlers, an animal ethologist, wildlife veterinarian, wildlife rehabilitation specialist and an animal rights advocacy group representative. Individual representatives nominated a range of welfare concerns, and 15 were identified for discussion and prioritisation. The leading welfare concern was a lack of governance and regulation within the industry. Participants agreed on nine non-negotiable practices affecting welfare concerns, which included ethical concerns, such as cubs exiting into the ranching industry (farming of lions for hunting) and the bone trade (lions being slaughtered for their bones, which are exported for lion bone wine) once petting age has passed. Welfare concerns representative of current management practices within the lion cub interaction industry were compared for importance using an online adaptive conjoint analysis survey of 60 stakeholders in the industry. The survey identified the most important welfare concerns to be poor social grouping of cubs, an inability for cubs to choose their own environment and retreat from a forced interaction, a lack of trained and dedicated caretakers, and poor breeding practices. The conjoint analysis survey results produced a value model, which can be used as a tool to score cubs’ welfare in interaction facilities, and it identified unacceptable practices lacking welfare consideration.
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Otová, B., M. Sladká, J. Damoiseaux, A. Panczak, V. Mandys, K. Francová, and M. Kudláčková. "Characterization of T-cell lymphomas in the Prague inbred Sprague-Dawley/cub rat strain: a model of spontaneous hematologic malignancy." Transplantation Proceedings 31, no. 3 (May 1999): 1618–19. http://dx.doi.org/10.1016/s0041-1345(99)00059-7.
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Verma, Vinay Kumar, Dhanajit Brahma, and Piyush Rai. "Meta-Learning for Generalized Zero-Shot Learning." Proceedings of the AAAI Conference on Artificial Intelligence 34, no. 04 (April 3, 2020): 6062–69. http://dx.doi.org/10.1609/aaai.v34i04.6069.
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Learning to classify unseen class samples at test time is popularly referred to as zero-shot learning (ZSL). If test samples can be from training (seen) as well as unseen classes, it is a more challenging problem due to the existence of strong bias towards seen classes. This problem is generally known as generalized zero-shot learning (GZSL). Thanks to the recent advances in generative models such as VAEs and GANs, sample synthesis based approaches have gained considerable attention for solving this problem. These approaches are able to handle the problem of class bias by synthesizing unseen class samples. However, these ZSL/GZSL models suffer due to the following key limitations: (i) Their training stage learns a class-conditioned generator using only seen class data and the training stage does not explicitly learn to generate the unseen class samples; (ii) They do not learn a generic optimal parameter which can easily generalize for both seen and unseen class generation; and (iii) If we only have access to a very few samples per seen class, these models tend to perform poorly. In this paper, we propose a meta-learning based generative model that naturally handles these limitations. The proposed model is based on integrating model-agnostic meta learning with a Wasserstein GAN (WGAN) to handle (i) and (iii), and uses a novel task distribution to handle (ii). Our proposed model yields significant improvements on standard ZSL as well as more challenging GZSL setting. In ZSL setting, our model yields 4.5%, 6.0%, 9.8%, and 27.9% relative improvements over the current state-of-the-art on CUB, AWA1, AWA2, and aPY datasets, respectively.
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Muia, Joshua, Jian Zhu, Suellen Greco, Karen Vanhoorelbeke, Louis Deforche, Lisa Westfield, Garima Tyagi, and J. Evan Sadler. "Phylogenetic Analysis Identifies a Subset of ADAMTS13 Domains That Are Highly Conserved and Essential for Allosteric Regulation." Blood 128, no. 22 (December 2, 2016): 1385. http://dx.doi.org/10.1182/blood.v128.22.1385.1385.
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Abstract Introduction: Human ADAMTS13 has metalloprotease (M), disintegrin-like (D), thrombospondin-1 (T), Cys-rich (C) and spacer (S) domains (proximal domains), followed by 7 T and 2 CUB domains (distal domains).ADAMTS13 regulates von Willebrand factor (VWF) by cleaving a Tyr-Met bond in the VWF A2 domain that is exposed under shear force. Acquired or inherited ADAMTS13 deficiency impairs this regulatory mechanism and cause thrombotic thrombocytopenic purpura (TTP), a life threatening disorder. We recently showed that ADAMTS13 is autoinhibited by its distal T8-CUB domains and this inhibition is relieved by binding to VWF. Thus, VWF promotes its own destruction by allosterically activating ADAMTS13. We investigated the evolution and conservation of this remarkable regulatory mechanism. Methods:ADAMTS13 cDNA sequences for >300 species were assembled from genome assemblies and SRA transcriptomic and genomic data. Recombinant ADAMTS13 variants were expressed in HEK293 cells and purified chromatographically. Plasma was obtained from dog, armadillo, rabbit, primates (human, baboon, marmoset, macaque), rodents (rat, mouse), ungulates (cattle, sheep, pig, horse), birds (chicken, pigeon), and Xenopus laevis. Plasma ADAMTS13 activity of at least three members of each species was assayed with human-FRETS71, a fluorogenic ADAMTS13 substrate based on human VWF. Similar fluorogenic substrates were prepared with armadillo, rat, pigeon and cattle VWF sequences. Plasma ADAMTS13 also was assayed with allosteric activators of human ADAMTS13: monoclonal antibodies (MAbs) against distal T and CUB domains, low pH (pH 6), and recombinant human VWF D4 domain. ADAMTS13-VWF interactions were assessed with biolayer interferometry (BLI) and binding data fitted to 1:1 binding model. Results: The ancestral ADAMTS13 had a long propeptide that is characteristic of most metalloproteases but notably missing from human ADAMTS13, and 8 distal T domains compared to 7 distal T domains in human ADAMTS13. The ancestral structure today is found in most reptiles, amphibians, and marsupials. The propeptide, T3, T4, T6 and T6a have been deleted independently several times in mammals, birds, amphibians and fish. Most animal plasmas cleaved human-FRETS71 less rapidly than human plasma, although armadillo, rabbit, and dog were 2.4-, 3.0-, 4.0-fold more active, respectively. Human and cattle VWF have Tyr-Met cleavage sites, but armadillo VWF has a Tyr-Leu bond. Armadillo plasma cleaved armadillo-FRETS71 and human-FRETS71 at a similar rate; other species cleaved armadillo-FRETS71 15% to 88% as rapidly as human-FRETS71. Surprisingly, cattle-FRETS71 was cleaved ~2- to 15-fold faster than human-FRETS71 by most plasmas. Except for C57Bl/6 mice (which have ADAMTS13 truncated after T6), armadillo, and dog, all plasmas screened were activated by MAbs or VWF D4. Frog and pigeon ADAMTS13 were activated ~6-fold by D4, whereas human ADAMTS13 was activated only 2-fold. Absence of CUB domains in armadillo ADAMTS13 abolished activation by D4. In contrast, absence of all but 3 distal T domains in pigeon ADAMTS13 did not impair activation by VWF D4. Recombinant human ADAMTS13 constructed with deletions like those in armadillo and pigeon ADAMTS13 had similar properties: delT3-6 was activated by VWF D4 but M-T8 was not. All enzymes activated by VWF D4 showed enhanced cleavage of multimeric VWF under fluid shear stress compared to enzymes that are not activated by VWF D4 (Figure 1 and Table 1). When normalized for activity toward FRETS71, pigeon ADAMTS13 was ~2-fold more specific for VWF multimers than is human ADAMTS13. In agreement with the cleavage data, recombinant human and pigeon ADAMTS13, and MT-8 bound VWF D4-CK with Kd values in the 350-840 nM range, whereas MDTCS, MT-7 and delT2-7 did not bind. Conclusion: Allosteric regulation of ADAMTS13 by VWF is broadly conserved, with some apparent exceptions. The distal T3-T6 domains are dispensable for allosteric regulation, whereas T7, T8 and CUB domains are required. Furthermore, ADAMTS13 from different species exhibits striking variation in substrate specificity. For most species, altering the sequence of the VWF substrate can markedly increase the rate of cleavage, indicating that ADAMTS13 and VWF have not evolved to be optimal enzyme-substrate pairs. These properties are likely to reflect evolutionary pressure to balance the risk of VWF-dependent bleeding and thrombosis. Disclosures Sadler: Ablynx: Consultancy; 23andMe: Consultancy; BioMarin: Consultancy.
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Schmidt, Tristan. "Father and son like eagle and eaglet – concepts of animal species and human families in Byzantine court oration (11th/12th c.)." Byzantinische Zeitschrift 112, no. 3 (August 1, 2019): 959–90. http://dx.doi.org/10.1515/bz-2019-0039.
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Abstract The idea that physical features and character traits are inherited from ancestors is central to the self-identification and representation of pre-modern elites. For the 12th-century Byzantine aristocracy, the idea of family and ancestry was of major importance. Members of the military elite frequently had themselves depicted as the latest scions of a lineage of brave warriors. The ruling Komnenoi and Angeloi tried to establish dynastic claims to the throne by presenting their families as being more fit to rule than any other. To support these claims, panegyrists turned to nature in search of legitimizing comparanda. The idea that animal species reproduce unchanged and pass on their specific traits from one generation to the next, provided a suitable model. Comparisons of emperors or aristocrats and their sons with lion and lion cub or eagle and eaglet were popular images in court poetry. Through a detailed examination of this imagery, the paper exemplifies how writers and orators made use of theories from ancient/medieval natural science and created legitimizing models for socio-political needs.