799 research outputs found
Completing right-censored data in time-series modelling
No full text2019 International Conference on Artificial Intelligence and Data Processing Symposium, IDAP 2019, 21 September 2019 through 22 September 2019, , 153040This paper focuses on nonparametric regression modelling of time series observations with data irregularities, such as censoring due to a cutoff value. In general, researchers do not prefer to put up with censored cases in time series analyses because their results are generally biased. In this paper, we present two imputation algorithms for handling auto-correlated censored data: Artificial neural network based imputation and Gaussian imputation. These algorithms provide an estimation of the censored data points and replace them with their estimates. After the imputation procedure, the right-censored time series data is modelled and the performance of imputation methods are monitored. Thus, the effect of two imputation methods is evaluated for both modelling and completing censored observations. The purpose of this study is to prepare the censored data set for analysis without manipulating the observed part of the data such as synthetic data transformation or Kaplan-Meier weights. In this paper, algorithms for two methods are given and imputation processes are expressed. © 2019 IEEE
2‐(Methyl(phenyl)amino)‐N‐(phenyloxyphenyl)acetamide structural motif representing a framework for selective SIRT2 inhibition
No full text: The mammalian cytoplasmic protein SIRT2, a class III histone deacetylase family member, possesses NAD+-dependent lysine deacetylase/deacylase activity. Dysregulation of SIRT2 has been implicated in the pathogenesis of several diseases, including neurological and metabolic disorders and cancer; thus, SIRT2 emerges as a potential therapeutic target. Herein, we identified a series of diaryl acetamides (ST61-ST90) by the structural optimization of our hit STH2, followed by enhanced SIRT2 inhibitory potency and selectivity. Among them, ST72, ST85, and ST88 selectively inhibited SIRT2 with IC50 values of 9.97, 5.74, and 8.92 μM, respectively. Finally, the entire study was accompanied by in silico prediction of binding modes of docked compounds and the stability of SIRT2-ligand complexes. We hope our findings will provide substantial information for designing selective inhibitors of SIRT2
ABRF Proteome Informatics Research Group (iPRG) 2015 Study: Detection of Differentially Abundant Proteins in Label-Free Quantitative LC-MS/MS Experiments
No full textWOS: 000393539600054PubMed ID: 27990823Detection of differentially abundant proteins in label-free quantitative shotgun liquid chromatography tandem mass spectrometry (LC-MS/MS) experiments requires a series of computational steps that identify and quantify LC-MS features. It also requires statistical analyses that distinguish systematic changes in abundance between conditions from artifacts of biological and technical variation. The 2015 study of the Proteome Informatics Research Group (iPRG) of the Association of Biomolecular Resource Facilities (ABRF) aimed to evaluate the effects of the statistical analysis on the accuracy of the results. The study used LC tandem mass spectra acquired from a controlled mixture, and made the data available to anonymous volunteer participants. The participants used methods of their choice to detect differentially abundant proteins, estimate the associated fold changes, and characterize the uncertainty of the results. The study found that multiple strategies (including the use of spectral counts versus peak intensities, and various software tools) could lead to accurate results, and that the performance was primarily determined by the analysts' expertise. This manuscript summarizes the outcome of the study, and provides representative examples of good computational and statistical practice. The data set generated as part of this study is publicly available.NIH NINDSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Neurological Disorders & Stroke (NINDS) [P30 NS050276]; National Institute of General Medical SciencesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [R01GM087221]; Center for Systems Biology [2P50 GM076547]; ABRF; NIH Shared Instrumentation GrantUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [RR027990]; NATIONAL CENTER FOR RESEARCH RESOURCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Center for Research Resources (NCRR) [S10RR027990] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [P50GM076547, P50GM076547, P50GM076547, R01GM087221, P50GM076547, R01GM087221, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, R01GM087221, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, R01GM087221, P50GM076547, P50GM076547, P50GM076547, P50GM076547, R01GM087221, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, R01GM087221, P50GM076547, P50GM076547, R01GM087221, P50GM076547, P50GM076547, P50GM076547, R01GM087221, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, R01GM087221, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, R01GM087221, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547, P50GM076547] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Neurological Disorders & Stroke (NINDS) [P30NS050276, P30NS050276, P30NS050276, P30NS050276, P30NS050276, P30NS050276, P30NS050276, P30NS050276, P30NS050276, P30NS050276, P30NS050276, P30NS050276, P30NS050276, P30NS050276, P30NS050276, P30NS050276] Funding Source: NIH RePORTER; Direct For Computer & Info Scie & EnginrNational Science Foundation (NSF)NSF - Directorate for Computer & Information Science & Engineering (CISE) [1544542] Funding Source: National Science Foundation; Division of Computing and Communication FoundationsNational Science Foundation (NSF)NSF - Directorate for Computer & Information Science & Engineering (CISE) [1544542] Funding Source: National Science FoundationWe thank the participants of the iPRG 2015 study for their work in preparing the submissions. We thank Steven Blais and Jingjing Deng from the Neubert Lab (Mass Spectrometry Core for Neuroscience), Skirball Institute, NYU School of Medicine, for the LC-MS/MS analysis to produce the data for this study. We acknowledge support from the ABRF and NIH Shared Instrumentation Grant RR027990, NIH NINDS grant P30 NS050276, the National Institute of General Medical Sciences under grant R01GM087221, and 2P50 GM076547/Center for Systems Biology
In silico approach reveals N-(5-phenoxythiophen-2-yl)-2-(arylthio)acetamides as promising selective SIRT2 inhibitors: the case of structural optimization of virtual screening-derived hits
No full textEpigenetic modifications play an essential role in tumor suppression and promotion. Among the diverse range of epigenetic regulators, SIRT2, a member of NAD+-dependent protein deacetylates, has emerged as a crucial regulator of cellular processes, including cell cycle progression, DNA repair, and metabolism, impacting tumor growth and survival. In the present work, a series of N-(5-phenoxythiophen-2-yl)-2-(arylthio)acetamide derivatives were identified following a structural optimization of previously reported virtual screening hits, accompanied by enhanced SIRT2 inhibitory potency. Among the compounds, ST44 and ST45 selectively inhibited SIRT2 with IC50 values of 6.50 and 7.24 mu M, respectively. The predicted binding modes of the two compounds revealed the success of the optimization run. Moreover, ST44 displayed antiproliferative effects on the MCF-7 human breast cancer cell line. Further, the contribution of SIRT2 inhibition in this effect of ST44 was supported by western blotting, affording an increased alpha-tubulin acetylation. Furthermore, molecular dynamics (MD) simulations and binding free energy calculations using molecular mechanics/generalized born surface area (MM-GBSA) method evaluated the accuracy of predicted binding poses and ligand affinities. The results revealed that ST44 exhibited a remarkable level of stability, with minimal deviations from its initial docking conformation. These findings represented a significant improvement over the virtual screening hits and may contribute substantially to our knowledge for further selective SIRT2 drug discovery
Çok kıymetli ve sevgili hocam Prof. Dr. Zeyyat Hatiboğlu
No full textEren, Erol (Dogus Author)Bu satırlarda içimden ne geliyorsa ve ne gibi duygular içindeysem onları yazıyorum. Değerli hocamın sağlığında çıkarmaya çalıştığımız bu armağan kitabında yer almasını arzu ettiğim düşünce ve duygularım kendisiyle yüz yüze kaldığımızda dahi söylemediğim şeylerdir
Localized cortical injections of ethosuximide suppress spike-and-wave activity and reduce the resistance to kindling in genetic absence epilepsy rats (GAERS)
No full textModels of genetic absence epilepsy are resistant to secondary generalization of focal limbic seizures. This correlates with the postnatal development of spike-and-wave discharges (SWDs), a hallmark of absence seizures arising from a cortical focus in the perioral region of somatosensory cortex. Ethosuximide injected at this site suppresses SWDs. The effect of this suppression on kindling in Genetic Absence Epilepsy Rats from Strasbourg (GAERS), has been compared for postnatal 30 day (PN30) rats having immature SWDs and adult (>4 months) rats having mature SWDs. Non-epileptic Wistar and GAERS rats were implanted with a basolateral amygdaloid stimulation electrode, bilateral injection cannulas into the cortical perioral focus, and cortical recording electrodes. Following recovery cortical injections of ethosuximide or saline were made and after 30 min rats were given 36 stimulations or until Racine's stage 5 seizures were produced. All Wistar rats (PN30 and adult) treated with saline or ethosuximide reached stage 5. Of GAERS given saline, 33% (PN30) and 43% (adults) were resistant to kindling; after ethosuximide pups behaved like Wistars, but adults showed a delay in kindling relative to Wistars. These findings imply that mechanisms underlying kindling resistance are related but not limited to SWD activity in animals with genetic absence epilepsy. (C) 2009 Elsevier B.V. All rights reserved
Büyük Dünya Endeksleri Kullanılarak BIST-100 Endeksi Değişim Yönünün Makine Öğrenmesi Algoritmaları ile Sınıflandırılması
No full textBorsa İstanbul 100 (BIST-100) endeksi, diğer büyük dünya endeksleri ile birlikte finans piyasalarının küreselleşme değişiminin bir parçası olmuştur. Endeksler arasındaki ilişkinin analizi yatırımcılara büyük avantajlar sağlayacaktır. Bu durumdan yola çıkarak çeşitli makine öğrenmesi algoritmaları ile büyük dünya endeksleri ve bazı makroekonomik göstergeler kullanılarak BIST-100 endeksinin değişim yönünün (artış-azalış) sınıflandırılması amaçlanmıştır. Bu amaç doğrultusunda BIST-100 endeksinin değişim yönünün sınıflandırmasında etkin rol oynayan değişkenler belirlenmiş ve belirlenen bu değişkenler yardımıyla sınıflandırma başarılarında değişim olup olmadığı incelenmiştir. Tüm değişkenler ile yapılan sınıflandırmada lojistik regresyonun %70,6; öznitelik seçimi ile yapılan sınıflandırmada da Destek Vektör Makinesi PUK çekirdeği algoritmasının %71,9 daha doğru sınıflandırma başarısı gösterdiği belirlenmiştir. Böylelikle daha az sayıda değişken ile daha yüksek sınıflandırma başarısı elde edilmiştir
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Author Correction: Bimetallic synergy in cobalt–palladium nanocatalysts for CO oxidation
No full textIn the version of this Article originally published, the author Baran Eren was mistakenly affiliated with the Harbin Institute of Technology, China; it has now been corrected to Materials Science Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA
Author's response: Ocular photodynamic therapy with verteporfin in pigmented and amelanotic choroidal melanoma
No full textCaspase-cleaved fragments of cytokeratin 18 in patients with chronic hepatitis B
No full textBackground: During hepatocyte apoptosis, intermediate filament protein cytokeratin 18 is cleaved by caspases at Asp396 which can be specifically detected by the monoclonal antibody M30 (M30-antigen). In this study, we sought to determine whether serum M30-antigen levels can serve as a useful biomarker of liver injury in the clinical spectrum of HBV infection. Methods: Serum M30-antigen levels were measured in inactive HBV carriers (n=54), patients with HBeAg-negative chronic hepatitis B (CHB. n=47), patients with HBeAg-positive CHB (n=42) and healthy controls (n=29). All subjects were treatment-nave. Results: There were significant differences in serum M30-antigen levels across the study groups (P<0.001; Kruskal-Wallis test). Post hoc analyses revealed that M30-antigen levels did not differ significantly between inactive HBV carriers (median 109.6 U/L) and healthy controls (median 106.1 U/L). However, both patients with HBeAg-negative (CHB, median 182.9 U/L, P<0.001) and HBeAg-positive CHB (median 158.3 UP., P<0.001) had significantly higher levels of M30-antigen compared with inactive HBV carriers. Conclusions: Hepatocyte apoptotic activity - as reflected by serum M30-antigen levels - is increased in chronic active hepatitis B, but is not associated with the HBeAg status. In contrast, apoptosis does not appear to be a prominent feature of inactive HBV carriers. (C) 2010 Elsevier B.V. All rights reserved
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