scholarly journals Comprehensive Analysis of Chemical Structures That Have Been Tested as CFTR Activating Substances in a Publicly Available Database CandActCFTR

2021 ◽  
Vol 12 ◽  
Author(s):  
Manuel Manfred Nietert ◽  
Liza Vinhoven ◽  
Florian Auer ◽  
Sylvia Hafkemeyer ◽  
Frauke Stanke
Keyword(s):  
Cystic Fibrosis ◽  
Chemical Space ◽  
Principal Component ◽  
The Body ◽  
Published Data ◽  
Software Environment ◽  
Related Substance ◽  
Ion Conductance ◽  
Chemical Structures ◽  
Bicarbonate Transporter

Background: Cystic fibrosis (CF) is a genetic disease caused by mutations in CFTR, which encodes a chloride and bicarbonate transporter expressed in exocrine epithelia throughout the body. Recently, some therapeutics became available that directly target dysfunctional CFTR, yet research for more effective substances is ongoing. The database CandActCFTR aims to provide detailed and comprehensive information on candidate therapeutics for the activation of CFTR-mediated ion conductance aiding systems-biology approaches to identify substances that will synergistically activate CFTR-mediated ion conductance based on published data.Results: Until 10/2020, we derived data from 108 publications on 3,109 CFTR-relevant substances via the literature database PubMed and further 666 substances via ChEMBL; only 19 substances were shared between these sources. One hundred and forty-five molecules do not have a corresponding entry in PubChem or ChemSpider, which indicates that there currently is no single comprehensive database on chemical substances in the public domain. Apart from basic data on all compounds, we have visualized the chemical space derived from their chemical descriptors via a principal component analysis annotated for CFTR-relevant biological categories. Our online query tools enable the search for most similar compounds and provide the relevant annotations in a structured way. The integration of the KNIME software environment in the back-end facilitates a fast and user-friendly maintenance of the provided data sets and a quick extension with new functionalities, e.g., new analysis routines. CandActBase automatically integrates information from other online sources, such as synonyms from PubChem and provides links to other resources like ChEMBL or the source publications.Conclusion: CandActCFTR aims to establish a database model of candidate cystic fibrosis therapeutics for the activation of CFTR-mediated ion conductance to merge data from publicly available sources. Using CandActBase, our strategy to represent data from several internet resources in a merged and organized form can also be applied to other use cases. For substances tested as CFTR activating compounds, the search function allows users to check if a specific compound or a closely related substance was already tested in the CF field. The acquired information on tested substances will assist in the identification of the most promising candidates for future therapeutics.

Principal Component Analysis of Chinese Porcelains from the Five Dynasties to the Qing Dynasty

1992 ◽  
Vol 47 (10) ◽  
pp. 1029-1033
Author(s):  
C. T. Yap ◽  
Younan Hua
Keyword(s):  
Principal Component Analysis ◽  
Song Dynasty ◽  
Principal Component ◽  
Component Analysis ◽  
Porcelain Body ◽  
The Body ◽  
Chemical Components ◽  
Published Data ◽  
Five Dynasties ◽  
Ming And Qing Dynasties

AbstractThis is a study of the possibility of identifying antique Chinese porcelains according to the period or dynasty, using major and minor chemical components (SiO2 , Al2O3 , Fe2O3 , K2O, Na2O, CaO and MgO) from the body of the porcelain. Principal component analysis is applied to published data on 66 pieces of Chinese procelains made in Jingdezhen during the Five Dynasties and the Song, Yuan, Ming and Qing Dynasties. It is shown that porcelains made during the Five Dynasties and the Yuan (or Ming) and Qing Dynasties can be segregated completely without any overlap. However, there is appreciable overlap between the Five Dynasties and the Song Dynasty, some overlap between the Song and Ming Dynasties and also between the Yuan and Ming Dynasties. Interestingly, Qing procelains are well separated from all the others. The percentage of silica in the porcelain body decreases and that of alumina increases with recentness with the exception of the Yuan and Ming Dynasties, where this trend is reversed.

The Impact of Shariah Governance and Corporate Governance on the Risk Management Practices: Evidence from Local and Foreign Islamic Banks in Malaysia

2018 ◽  
Vol 15 (2) ◽  
pp. 1-20
Author(s):  
Sabri Embi ◽  
Zurina Shafii
Keyword(s):  
Risk Management ◽  
Corporate Governance ◽  
Management Practices ◽  
Principal Component ◽  
T Test ◽  
The Body ◽  
Primary Data ◽  
Islamic Banks ◽  
Shariah Governance ◽  
The Impact

The purpose of this study is to examine the impact of Shariah governance and corporate governance (CG) on the risk management practices (RMPs) of local Islamic banks and foreign Islamic banks operating in Malaysia. The Shariah governance comprises the Shariah review (SR) and Shariah audit (SA) variables. The study also evaluates the level of RMPs, CG, SR, and SA between these two type of banks. With the aid of SPSS version 20, the items for RMPs, CG, SR, and SA were subjected to principal component analysis (PCA). From the PCA, one component or factor was extracted each for the CG, SR, and RMPs while another two factors were extracted for the SA. Primary data was collected using a self-administered survey questionnaire. The questionnaire covers four aspects ; CG, SR, SA, and RMPs. The data received from the 300 usable questionnaires were subjected to correlation and regression analyses as well as an independent t-test. The result of correlation analysis shows that all the four variables have large positive correlations with each other indicating a strong and significant relationship between them. From the regression analysis undertaken, CG, SR, and SA together explained 52.3 percent of the RMPs and CG emerged as the most influential variable that impacts the RMPs. The independent t-test carried out shows that there were significant differences in the CG and SA between the local and foreign Islamic banks. However, there were no significant differences between the two types of the bank in relation to SR and RMPs. The study has contributed to the body of knowledge and is beneficial to academicians, industry players, regulators, and other stakeholders.

It is better an approximate answer to the right question than the exact answer to the wrong question : the case of the psychometric analysis of the ASQ:SE

2020 ◽  
Author(s):  
Luis Anunciacao ◽  
janet squires ◽  
J. Landeira-Fernandez
Keyword(s):  
Internal Structure ◽  
Statistical Methods ◽  
Principal Component ◽  
Psychological Theory ◽  
Published Data ◽  
Multivariate Statistical ◽  
Exact Answer ◽  
Wide Range ◽  
Ages And Stages Questionnaire ◽  
The Right

One of the main activities in psychometrics is to analyze the internal structure of a test. Multivariate statistical methods, including Exploratory Factor analysis (EFA) and Principal Component Analysis (PCA) are frequently used to do this, but the growth of Network Analysis (NA) places this method as a promising candidate. The results obtained by these methods are of valuable interest, as they not only produce evidence to explore if the test is measuring its intended construct, but also to deal with the substantive theory that motivated the test development. However, these different statistical methods come up with different answers, providing the basis for different analytical and theoretical strategies when one needs to choose a solution. In this study, we took advantage of a large volume of published data (n = 22,331) obtained by the Ages and Stages Questionnaire Social-Emotional (ASQ:SE), and formed a subset of 500 children to present and discuss alternative psychometric solutions to its internal structure, and also to its subjacent theory. The analyses were based on a polychoric matrix, the number of factors to retain followed several well-known rules of thumb, and a wide range of exploratory methods was fitted to the data, including EFA, PCA, and NA. The statistical outcomes were divergent, varying from 1 to 6 domains, allowing a flexible interpretation of the results. We argue that the use of statistical methods in the absence of a well-grounded psychological theory has limited applications, despite its appeal. All data and codes are available at https://osf.io/z6gwv/.

scholarly journals Learning chemistry: exploring the suitability of machine learning for the task of structure-based chemical ontology classification

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Janna Hastings ◽  
Martin Glauer ◽  
Adel Memariani ◽  
Fabian Neuhaus ◽  
Till Mossakowski
Keyword(s):  
Machine Learning ◽  
Logistic Regression ◽  
Short Term Memory ◽  
Chemical Space ◽  
Chemical Data ◽  
Learning Approaches ◽  
Class Prediction ◽  
Chemical Structures ◽  
Chemical Ontology ◽  
Chemical Ontologies

AbstractChemical data is increasingly openly available in databases such as PubChem, which contains approximately 110 million compound entries as of February 2021. With the availability of data at such scale, the burden has shifted to organisation, analysis and interpretation. Chemical ontologies provide structured classifications of chemical entities that can be used for navigation and filtering of the large chemical space. ChEBI is a prominent example of a chemical ontology, widely used in life science contexts. However, ChEBI is manually maintained and as such cannot easily scale to the full scope of public chemical data. There is a need for tools that are able to automatically classify chemical data into chemical ontologies, which can be framed as a hierarchical multi-class classification problem. In this paper we evaluate machine learning approaches for this task, comparing different learning frameworks including logistic regression, decision trees and long short-term memory artificial neural networks, and different encoding approaches for the chemical structures, including cheminformatics fingerprints and character-based encoding from chemical line notation representations. We find that classical learning approaches such as logistic regression perform well with sets of relatively specific, disjoint chemical classes, while the neural network is able to handle larger sets of overlapping classes but needs more examples per class to learn from, and is not able to make a class prediction for every molecule. Future work will explore hybrid and ensemble approaches, as well as alternative network architectures including neuro-symbolic approaches.

scholarly journals Prevention of Advanced Cancer by Vitamin D3 Supplementation: Interaction by Body Mass Index Revisited

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1408
Author(s):  
Hermann Brenner ◽  
Sabine Kuznia ◽  
Clarissa Laetsch ◽  
Tobias Niedermaier ◽  
Ben Schöttker
Keyword(s):  
Body Mass Index ◽  
Vitamin D ◽  
Cancer Patients ◽  
Body Mass ◽  
Advanced Cancer ◽  
Vitamin D3 ◽  
Normal Weight ◽  
The Body ◽  
Published Data ◽  
Vitamin D3 Supplementation

Meta-analyses of randomized controlled trials (RCTs) have demonstrated a protective effect of vitamin D3 (cholecalciferol) supplementation against cancer mortality. In the VITAL study, a RCT including 25,871 men ≥ 50 years and women ≥ 55 years, protective effects of vitamin D3 supplementation (2000 IU/day over a median of 5.3 years) with respect to incidence of any cancer and of advanced cancer (metastatic cancer or cancer death) were seen for normal-weight participants but not for overweight or obese participants. We aimed to explore potential reasons for this apparent variation of vitamin D effects by body mass index. We conducted complementary analyses of published data from the VITAL study on the association of body weight with cancer outcomes, stratified by vitamin D3 supplementation. Significantly increased risks of any cancer and of advanced cancer were seen among normal-weight participants compared to obese participants in the control group (relative risk (RR), 1.27; 95% confidence interval (CI), 1.07–1.52, and RR, 1.44; 95% CI, 1.04–1.97, respectively). No such patterns were seen in the intervention group. Among those with incident cancer, vitamin D3 supplementation was associated with a significantly reduced risk of advanced cancer (RR, 0.86; 95% CI, 0.74–0.99). The observed patterns point to pre-diagnostic weight loss of cancer patients and preventive effects of vitamin D3 supplementation from cancer progression as plausible explanations for the body mass index (BMI)—intervention interactions. Further research, including RCTs more comprehensively exploring the potential of adjuvant vitamin D therapy for cancer patients, should be pursued with priority.

scholarly journals The effects of nano-curcumin as a nutritional strategy on clinical and inflammatory factors in children with cystic fibrosis: the study protocol for a randomized controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Saeedeh Talebi ◽  
Mahammad Safarian ◽  
Mahmood Reza Jaafari ◽  
Seyed Javad Sayedi ◽  
Zahra Abbasi ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Controlled Trial ◽  
Genetic Disorder ◽  
The Body ◽  
Inflammatory Factors ◽  
Secondary Outcome ◽  
Nasopharyngeal Swab ◽  
Nutritional Strategy ◽  
Cftr Protein ◽  
The Impact

Abstract Background Cystic fibrosis (CF) is a genetic disorder, which is caused by the CFTR protein defects. Along with CFTR dysfunction, inflammation plays a key role in the disease outcomes. Inflammation may develop due to the internal dysfunction of the CFTR protein or external factors. Curcumin affects the CFTR protein function primarily as a corrector and potentiator and secondary as an anti-inflammatory and antimicrobial agent. The present study aims to assess the impact of nano-curcumin on clinical and inflammatory markers in children with CF. Methods This prospective, double blind control trial will be conducted at the Akbar Children’s Hospital in Mashhad, Iran. Children with CF will be enrolled based on the eligibility criteria. Placebo and curcumin with the maximum dose of 80 mg considering the body surface of the patients will be administrated for 3 months. The primary outcome is to evaluate inflammation based on serum interleukin-6, interleukin-10, and hs-CRP, stool calprotectin, and neutrophil count of nasopharyngeal swab. The secondary outcome involved clinical assessment via spirometry, anthropometrics, and quality of life. They will be assessed before and after 3 months. Discussion Due to the multifarious effects of curcumin on CF disease, it could be proposed as a nutritional strategy in the treatment of cystic fibrosis. Trial registration Iranian Registry of Clinical Trials IRCT20200705048018N1. Registered on July 10, 2020.

Design and operation of a tripod walking robot via dynamics simulation

Robotica ◽  
2010 ◽  
Vol 29 (5) ◽  
pp. 733-743 ◽  
Author(s):  
Conghui Liang ◽  
Hao Gu ◽  
Marco Ceccarelli ◽  
Giuseppe Carbone
Keyword(s):  
Mechanical Design ◽  
Low Cost ◽  
Three Dimensional ◽  
The Body ◽  
Dynamics Simulation ◽  
Walking Ability ◽  
Walking Robot ◽  
Three Dimensional Model ◽  
Software Environment ◽  
Leg Mechanisms

SUMMARYA mechanical design and dynamics walking simulation of a novel tripod walking robot are presented in this paper. The tripod walking robot consists of three 1-degree-of-freedom (DOF) Chebyshev–Pantograph leg mechanisms with linkage architecture. A balancing mechanism is mounted on the body of the tripod walking robot to adjust its center of gravity (COG) during walking for balancing purpose. A statically stable tripod walking gait is performed by synchronizing the motions of the three leg mechanisms and the balancing mechanism. A three-dimensional model has been elaborated in SolidWorks® engineering software environment for a characterization of a feasible mechanical design. Dynamics simulation has been carried out in the MSC.ADAMS® environment with the aim to characterize and to evaluate the dynamic walking performances of the proposed design with low-cost easy-operation features. Simulation results show that the proposed tripod walking robot with proper input torques, gives limited reaction forces at the linkage joints, and a practical feasible walking ability on a flatten ground.

Optimal Genetic Screening for Cystic Fibrosis

2021 ◽  
Author(s):  
Hussein El Hajj ◽  
Douglas R. Bish ◽  
Ebru K. Bish
Keyword(s):  
Cystic Fibrosis ◽  
Genetic Variants ◽  
Genetic Screening ◽  
Genetic Diseases ◽  
The United States ◽  
Published Data ◽  
Decision Support Model ◽  
Screening Process ◽  
Public Health Initiative ◽  
Cystic Fibrosis Screening

Improving Newborn Screening for Genetic Diseases Screening newborns for life-threatening genetic diseases is an important public health initiative. Cystic fibrosis is one of the most prevalent diseases in this context. As part of the cystic fibrosis screening process, all states in the United States use multiple tests, including genetic tests that detect a subset of the more than 300 genetic variants (specific mutations) that cause cystic fibrosis. In “Optimal Genetic Screening for Cystic Fibrosis,” El-Hajj, D.R. Bish, and E.K. Bish develop a decision support model to select which genetic variants to screen for, considering the trade-off between classification accuracy and testing cost, and the technological constraints that limit the number of variants selected. Because variant prevalence rates are highly uncertain, a robust optimization framework is developed. Further, two commonly used cystic fibrosis screening processes are analytically compared, and conditions under which each process dominates are established. A case study based on published data are provided.

scholarly journals Efforts to emulate human milk oligosaccharides

2007 ◽  
Vol 98 (S1) ◽  
pp. S74-S79 ◽  
Author(s):  
Rosa María Espinosa ◽  
Martha Taméz ◽  
Pedro Prieto
Keyword(s):  
Breast Milk ◽  
Human Milk ◽  
Current Knowledge ◽  
Biological Effects ◽  
Historical Context ◽  
Published Data ◽  
Human Milk Oligosaccharides ◽  
Milk Oligosaccharides ◽  
Fast Analysis ◽  
Chemical Structures

Research on human milk oligosaccharides (HMO) began with the characterisation of their chemical structures and is now focused on the elucidation of their biological roles. Previously, biological effects could only be investigated with fractions or structures isolated from breast milk; consequently, clinical observations were limited to comparisons between outcomes from breast-fed infants and their formula-fed counterparts. In some cases, it was inferred that the observed differences were caused by the presence of HMO in breast milk. Presently, analytical techniques allow for the fast analysis of milk samples, thus providing insights on the inherent variability of specimens. In addition, methods for the synthesis of HMO have provided single structures in sufficient quantities to perform clinical studies with oligosaccharide-supplemented formulae. Furthermore, studies have been conducted with non-mammalian oligosaccharides with the purpose of assessing the suitability of these structures to functionally emulate HMO. Taken together, these developments justify summarising current knowledge on HMO to further discussions on efforts to emulate human milk in regard to its oligosaccharide content. The present account summarises published data and intends to provide an historical context and to illustrate the state of the field.

scholarly journals A Novel Cystic Fibrosis Gene Mutation C.4242+1G>C in an Omani Patient: A Case Report

2021 ◽  
Vol 36 (2) ◽  
pp. e243-e243
Author(s):  
Said Al Balushi ◽  
Younis Al Balushi ◽  
Moza Al Busaidi ◽  
Latifa Al Mutawa
Keyword(s):  
Cystic Fibrosis ◽  
Gene Mutation ◽  
Digestive System ◽  
The Body ◽  
Cystic Fibrosis Gene ◽  
Cftr Gene ◽  
Sweat Test ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Cystic Fibrosis Transmembrane

Cystic fibrosis (CF) is a genetic disease caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that affects multisystems in the body, particularly the lungs and digestive system. We report a case of an Omani newborn who presented with meconium ileus and high suspicion of CF. Thus, full CFTR gene sequencing was performed, which revealed a homozygous unreported C.4242+1G>C novel gene mutation. Both parents were found to be heterozygous for this mutation. This case sheds light on the importance of the extensive genetic testing of typical CF cases in the absence of family history or during neonatal presentations, especially when the sweat test cannot be performed and the diagnosis can be challenging.

Sign in / Sign up

Export Citation Format

Share Document