scholarly journals DomainScope: A disease network based on protein domain connections

2019 ◽  
Author(s):  
Alin Voskanian-kordi ◽  
Ashley Funai ◽  
Maricel G. Kann
Keyword(s):  
Drug Repurposing ◽  
The Other ◽  
Protein Domain ◽  
Gene Variant ◽  
Disease Network ◽  
Disease Category ◽  
Significant Information ◽  
Subject Categories ◽  
Domain Variation ◽  
Domain Variant

AbstractProtein domains are highly conserved functional units of proteins. Because they carry functionally significant information, the majority of the coding disease variants are located on domains. Additionally, domains are specific units of the proteins that can be targeted for drug delivery purposes. Here, using information about variants sites associated with diseases, a disease network was built, based on their sharing the same domain and domain variation site. The result was 49,990 disease pairs linked by domain variant site and 533,687 disease pairs that share the same mutated domain. These pairs were compared to disease pairs made using previous methods such as gene identity and gene variant site identity, which revealed that over 8,000 of these pairs were not only missing from the gene pairings but also not found commonly together in literature. The disease network was analyzed from their disease subject categories, which when compared to the gene-based disease network revealed that the domain method results in higher number of connections across disease categories versus within a disease category. Further, a study into the drug repurposing possibilities of the disease network created using domain revealed that 16,902 of the disease pairs had a drug reported for one disease but not the other, highlighting the drug repurposing potential of this new methodology.

Mining Bug Report Repositories to Identify Significant Information for Software Bug Fixing

2021 ◽  
Author(s):  
Bancha Luaphol ◽  
Jantima Polpinij ◽  
Manasawee Kaenampornpan
Keyword(s):  
The Other ◽  
Problem Domain ◽  
Significant Information ◽  
Bug Reports ◽  
Bug Fixing ◽  
Classification Technique ◽  
Bug Report ◽  
Multiple Issues ◽  
Improved Accuracy ◽  
Software Bug

Most studies relating to bug reports aims to automatically identify necessary information from bug reports for software bug fixing. Unfortunately, the study of bug reports focuses only on one issue, but more complete and comprehensive software bug fixing would be facilitated by assessing multiple issues concurrently. This becomes a challenge in this study, where it aims to present a method of identifying bug reports at severe level from a bug report repository, together with assembling their related bug reports to visualize the overall picture of a software problem domain. The proposed method is called “mining bug report repositories”. Two techniques of text mining are applied as the main mechanisms in this method. First, classification is applied for identifying severe bug reports, called “bug severity classification”, while “threshold-based similarity analysis” is then applied to assemble bug reports that are related to a bug report at severe level. Our datasets are from three opensource namely SeaMonkey, Firefox, and Core:Layout downloaded from the Bugzilla. Finally, the best models from the proposed method are selected and compared with two baseline methods. For identifying severe bug reports using classification technique, the results show that our method improved accuracy, F1, and AUC scores over the baseline by 11.39, 11.63, and 19% respectively. Meanwhile, for assembling related bug reports using threshold-based similarity technique, the results show that our method improved precision, and likelihood scores over the other baseline by 15.76, and 9.14% respectively. This demonstrate that our proposed method may help increasing chance to fix bugs completely.

scholarly journals Target identification among known drugs by deep learning from heterogeneous networks

2020 ◽  
Vol 11 (7) ◽  
pp. 1775-1797 ◽  
Author(s):  
Xiangxiang Zeng ◽  
Siyi Zhu ◽  
Weiqiang Lu ◽  
Zehui Liu ◽  
Jin Huang ◽  
...  
Keyword(s):  
Deep Learning ◽  
Heterogeneous Networks ◽  
Target Identification ◽  
Drug Repurposing ◽  
Disease Network ◽  
The Relationship

Target identification and drug repurposing could benefit from network-based, rational deep learning prediction, and explore the relationship between drugs and targets in the heterogeneous drug–gene–disease network.

MAP UNITS IN CONTROLLED AND UNCONTROLLED LEGENDS ON SOME CANADIAN SOIL MAPS

1980 ◽  
Vol 60 (3) ◽  
pp. 511-516 ◽  
Author(s):  
K. W. G. VALENTINE ◽  
D. CHANG
Keyword(s):  
Small Proportion ◽  
The Other ◽  
Soil Maps ◽  
Land Area ◽  
Significant Information ◽  
Small Areas ◽  
Other Hand

The map index linkages (from CanSIS cartographic file) of seven soil maps were analyzed to find out how many map delineations represented each map unit and what proportion of the map they covered. Many map units were represented by only one or two delineations. This was more true for uncontrolled than controlled legends (51–85% of map units in uncontrolled legends versus 27–37% of map units in controlled legends). In both types of map the map units that had only one or two delineations covered only a small proportion of the land area. On the other hand, only a small proportion of the map units (between 14 and 31%) was needed to cover 75% of the land area in both types of maps. It proved possible to reduce the number of map units in one map with an uncontrolled legend from 193 to 91. This was done, firstly, by combining map units that represented only very small areas (or were represented by only one delineation) with larger map units that were very similar for the purpose of the survey. Secondly, map units were combined when more than 85% of the soils within them were the same. Controlled legends need not be very long and need not omit significant information.

scholarly journals Ribosomal protein L7a binds RNA through two distinct RNA-binding domains

2004 ◽  
Vol 385 (1) ◽  
pp. 289-299 ◽  
Author(s):  
Giulia RUSSO ◽  
Monica CUCCURESE ◽  
Gianluca MONTI ◽  
Annapina RUSSO ◽  
Angela AMORESANO ◽  
...  
Keyword(s):  
Ribosomal Protein ◽  
Rna Binding ◽  
Limited Proteolysis ◽  
Ribosomal Subunit ◽  
The Other ◽  
Protein Domain ◽  
Binding Motif ◽  
Nucleic Acid Binding ◽  
Binding Domains ◽  
Rna Binding Domains

The human ribosomal protein L7a is a component of the major ribosomal subunit. We previously identified three nuclear-localization-competent domains within L7a, and demonstrated that the domain defined by aa (amino acids) 52–100 is necessary, although not sufficient, to target the L7a protein to the nucleoli. We now demonstrate that L7a interacts in vitro with a presumably G-rich RNA structure, which has yet to be defined. We also demonstrate that the L7a protein contains two RNA-binding domains: one encompassing aa 52–100 (RNAB1) and the other encompassing aa 101–161 (RNAB2). RNAB1 does not contain any known nucleic-acid-binding motif, and may thus represent a new class of such motifs. On the other hand, a specific region of RNAB2 is highly conserved in several other protein components of the ribonucleoprotein complex. We have investigated the topology of the L7a–RNA complex using a recombinant form of the protein domain that encompasses residues 101–161 and a 30mer poly(G) oligonucleotide. Limited proteolysis and cross-linking experiments, and mass spectral analyses of the recombinant protein domain and its complex with poly(G) revealed the RNA-binding region.

scholarly journals The magnetic survey of the early Scythian burial site and settlements in the Turan-Uyuk valley in Tuva

2020 ◽  
Vol 55 ◽  
pp. 343-368
Author(s):  
Łukasz Oleszczak ◽  
Marcin M. Przybyła ◽  
Igor Pieńkos ◽  
Konstantin V. Chugunov ◽  
Nina A. Zhogova
Keyword(s):  
Russian Federation ◽  
Spatial Arrangement ◽  
The Other ◽  
Magnetic Survey ◽  
Archaeological Excavation ◽  
Burial Site ◽  
Significant Information ◽  
Non Invasive ◽  
Other Hand ◽  
Rule Out

In 2019, Polish archaeologists took part in an expedition of the Hermitage Museum, led by K.V. Chugunov, in Chinge-Tey cemetery, Tuva (Russian Federation). This paper presents the results of magnetic surveys carried out within the so-called western chain of barrows and around the princely barrow of Chinge-Tey I. This method of non-invasive research is very well suited to the landscape and has produced a significant body of information. Among others, the survey of the western chain identified a stone mantle in barrow 8, which makes it different from other barrows from this group, whose mounds were built of earth. Another important result is the identification of a stone circle surrounding a cult feature (certainly associated with eschatological rituals) known as the northern complex. The presence of the circle came as a surprise for the investigators of the site, as it does not manifest itself at all on the surface of the site. On the other hand, worth noting is one negative result, which nevertheless allows for some conclusions, namely the lack of detectable anomalies connected with one of the tombs in the vicinity of Chinge-Tey I (barrow 15). Despite being clearly discernible in the landscape, and even more evident in LIDAR images, the barrow is invisible on images produced with a magnetometer. This means that one cannot rule out a possibility that other structures undetectable by magnetic surveys may be present within the investigated part of the cemetery. Nevertheless, one cannot but arrive at the conclusion that the results generated by the magnetic research provide significant information concerning the spatial arrangement of the cemetery and are helpful in planning of archaeological excavation.

Investigating the resolution of IP arrays using inverse theory

Geophysics ◽  
1995 ◽  
Vol 60 (5) ◽  
pp. 1326-1341 ◽  
Author(s):  
Les P. Beard ◽  
Alan C. Tripp
Keyword(s):  
Gaussian Noise ◽  
Joint Inversion ◽  
Synthetic Data ◽  
Inverse Solution ◽  
The Other ◽  
Inverse Theory ◽  
Significant Information ◽  
Array Data ◽  
Data Subject ◽  
Structure Inversion

Using a fast 2-D inverse solution, we examined the resolution of different resistivity/IP arrays using noisy synthetic data subject to minimum structure inversion. We compared estimated models from inversions of data from the dipole‐dipole, pole‐dipole, and pole‐pole arrays over (1) a dipping, polarizable conductor, (2) two proximate conductive, polarizable bodies, (3) a polarizable conductor beneath conductive overburden, and (4) a thin, resistive, polarizable dike. The estimated resistivity and polarizability models obtained from inversion of the dipole‐dipole data were usually similar to the pole‐dipole estimated models. In the cases examined, the estimated models from the pole‐pole data were more poorly resolved than the models from the other arrays. If pole‐pole resistivity data contain even a fraction of a percent of Gaussian noise, the transformation of such data through superposition to equivalent data of other array types may be considerably distorted, and significant information can be lost using the pole‐pole array. Though the gradient array is reputed to be more sensitive to dip than other arrays, it evidently contains little information on dip that does not also appear in dipole‐dipole data, for joint inversion of dipole‐dipole and gradient array data yields models virtually identical to those obtained from inversion of dipole‐dipole data alone.

scholarly journals Repurposing of antibiotics for clinical management of COVID-19: a narrative review

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Abdourahamane Yacouba ◽  
Ahmed Olowo-okere ◽  
Ismaeel Yunusa
Keyword(s):  
Antibiotic Resistance ◽  
Clinical Management ◽  
Bacterial Infections ◽  
Web Of Science ◽  
Drug Repositioning ◽  
Drug Repurposing ◽  
The Other ◽  
Pharmacological Agents ◽  
Antiviral Activities ◽  
Antiviral Mechanism

Abstract Background Drug repurposing otherwise known as drug repositioning or drug re-profiling is a time-tested approach in drug discovery through which new medical uses are being established for already known drugs. Antibiotics are among the pharmacological agents being investigated for potential anti-SARS-COV-2 activities. The antibiotics are used either to resolve bacterial infections co-existing with COVID-19 infections or exploitation of their potential antiviral activities. Herein, we aimed to review the various antibiotics that have been repositioned for the management of COVID-19. Methods This literature review was conducted from a methodical search on PubMed and Web of Science regarding antibiotics used in patients with COVID-19 up to July 5, 2020. Results Macrolide and specifically azithromycin is the most common antibiotic used in the clinical management of COVID-19. The other antibiotics used in COVID-19 includes teicoplanin, clarithromycin, doxycycline, tetracyclines, levofloxacin, moxifloxacin, ciprofloxacin, and cefuroxime. In patients with COVID-19, antibiotics are used for their immune-modulating, anti-inflammatory, and antiviral properties. The precise antiviral mechanism of most of these antibiotics has not been determined. Moreover, the use of some of these antibiotics against SARS-CoV-2 infection remains highly controversial and not widely accepted. Conclusion The heavy use of antibiotics during the COVID-19 pandemic would likely worsen antibiotic resistance crisis. Consequently, antibiotic stewardship should be strengthened in order to prevent the impacts of COVID-19 on the antibiotic resistance crisis.

scholarly journals Financial Borrowing by Local State-Owned Enterprises in Serbia: An Assessment of National Practice

2020 ◽  
Vol 9 (1) ◽  
pp. 45-59
Author(s):  
Branko Živanović ◽  
Katarina Đulić ◽  
Ana Jolović
Keyword(s):  
Local Governments ◽  
Local State ◽  
The Other ◽  
Bank Credit ◽  
Actual State ◽  
Annual Business ◽  
Information Asymmetries ◽  
Significant Information ◽  
Qualitative And Quantitative ◽  
Credit Analysis

AbstractSerbian local state-owned enterprises (SOEs) owed in excess of EUR 220mn in late 2015, with estimates reaching a much higher figure. According to the national Fiscal Council, underinvestment by local governments amounted to some EUR 250mn annually. This paper looks at insufficient commercial borrowing by local SOEs trying to identify the causes of this financing gap by looking at two aspects: on one hand, we look at quantitative and qualitative inputs provided by local SOEs for credit analysis that may cause significant information asymmetries, and, on the other, we consider the possibility that bank credit analyses, even if done properly, could reveal that these firms are unable to borrow from banks.The research has revealed that the length and efficiency of the bank credit approval process is dictated by: the need to properly organise qualitative and quantitative SOE information and ensure that it reflects the actual state of affairs; the poor quality of financial statements of SOEs and their pro forma annual business planning and reporting; a common lack of appropriate revaluation of future income; and an existent drawback related to ownership over fixed assets that are considered as a public property in Serbia (rather than as a property of the SOE that uses them).On the other hand, banks do not distinguish sufficiently between private firms and SOEs. This does not allow banks to account for issues specific to SOEs such as the spillover of fiscal risk, corporate governance, relationships between the owner and its SOEs, economic and social objectives, and the like. The frequent inability of local SOEs to provide mortgages as collateral, coupled with the restriction on guarantees from local governments, nearly completely preclude lending for large-scale and long-term investment.We conclude that local SOEs have a limited access to finance due to information asymmetries caused by unsuitable qualitative and quantitative inputs made by SOEs in the credit analysis process. Nevertheless, appropriate credit analyses reveal that these companies can be able to borrow commercially, especially in lower amounts and at shorter maturities which could mitigate underinvestment by local SOEs.

scholarly journals Imprecise descriptions of Passiflora riparia Martius ex Masters led to redundant descriptions as P. emiliae Sacco, P. crenata Feuillet & Cremers, P. pergrandis Holm-Nielsen & Lawesson and P. fernandezii Escobar

PhytoKeys ◽  
2019 ◽  
Vol 117 ◽  
pp. 9-35
Author(s):  
Maxime Rome ◽  
Geo Coppens d’Eeckenbrugge
Keyword(s):  
South America ◽  
Central America ◽  
Amazon Basin ◽  
The Other ◽  
Similar Species ◽  
Tropical Andes ◽  
Significant Information ◽  
Closely Related Species ◽  
Marked Preference ◽  
Riparian Habitats

Passiflorariparia was incompletely described by Masters, who cited specimens of Martius and Spruce. While Spruce 2191, the unique syntype with an observable corona, exhibits a reduced outermost series of filaments, the accompanying iconography represents two equal outer series. Later descriptions have neither added significant information nor corrected the inconsistency in the corona description, so that four closely related species have been distinguished on the basis of traits not properly documented for P.riparia: P.emiliae (unequal outer series of filaments), P.crenata (bract color), P.pergrandis (flower size and sepal awn length), and P.fernandezii (hypanthium pubescence and shape). The present study compares (i) the descriptions of the above-mentioned taxa and (ii) 43 associated vouchers, as well as live specimens from two associated P.crenata populations. These and other specimens were georeferenced for a comparison of their distribution and habitat. Of the five P.riparia descriptions found in floras, only that of the Flora of Ecuador appears clearly divergent, corresponding in fact to P.tolimana. Those of the four other taxa only differ by unequal corona filaments (except for P.crenata) and the pubescence of floral parts. However, 22 vouchers associated with all these descriptions (including 16 for P.riparia), as well as the live specimens, share both these traits; the other 21 vouchers were uninformative and/or could not be assigned to any of the five species. The wider sample of 62 specimens indicates no significant differences in either geographic or in climatic distribution (lowlands of the Amazon basin), and a marked preference for riparian habitats. Thus, their very close morphology and ecology justify the placement of P.emiliae, P.crenata, P.pergrandis and P.fernandezii as synonyms of P.riparia, designating Spruce 2191 as epitype. The most similar species, P.ambigua (20 specimens mapped), differs in corolla and bract color, as well as a distribution centered along the tropical Andes of South America and in Central America, in more diverse habitats.

Distinct Profile of FLT3 Mutations in Brazil.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4532-4532
Author(s):  
Danielle L.C.F. Souza ◽  
Ana Silvia G. Lima ◽  
Guilherme A.A. Santos ◽  
Lidiane C. Melato ◽  
Adriana I. Dore ◽  
...  
Keyword(s):  
Point Mutations ◽  
Single Strand Conformation Polymorphism ◽  
Developed Countries ◽  
The Other ◽  
Protein Domain ◽  
Leukemic Cells ◽  
Tyrosine Kinase Receptor ◽  
Activation Loop ◽  
Flt3 Mutations ◽  
Exon 20

Abstract Mutations in the tyrosine kinase receptor FLT3 are the most common molecular abnormality in acute myeloid leukemia (AML) being detected in about 30% of AML cases. According to the protein domain altered FLT3 mutations may be classified as juxtamembrane or activation loop. The former are caused by internal tandem duplications (ITD) in exons 14 and 15 and is detected in 20–27% of AML patients. Mutations in the activation loop are mainly due to point mutations in exon 20 and is present in 5–7% of AML patients. Most of these mutations lead to changes in the aspartate in position 835 (D835), which have been detected in about 7% of AML cases. Both types of mutations cause the constitutive activation of FLT3 and are associated with bad prognosis. AML characteristics in Latin America are different from those in Europe and US. Namely, there is a higher frequency of acute promyelocytic leukemia (APL) and the clinical outcome of adult patients with other subtypes of AML treated with standard protocols is poorer. The worse prognosis seems to be related to the biology of the disease, rather than socio-economic features, based on studies of other hematological malignancies. In order to test if a higher frequency or different FLT3 mutations might explain these observations, we performed a screening for mutations in FLT3 using PCR and single strand conformation polymorphism (SSCP) techniques to evaluate exons 12 to 20, which encode for the intracytoplasmatic domains of the protein. Ninety-nine consecutive patients with AML (90 adults and 9 children) and 55 blood donors (controls) were analyzed. Two synonyms mutations that have not been previously described were detected: one in exon 12 (T526T) and the other in exon 17 (G697G). ITD mutations were detected in 23 (23.2%) patients with AML, therefore within the expected frequency based on the studies in developed countries. On the other hand, D835 mutations were absent, and except for a mutation detected in one patient causing the deletion of the aminoacid in the position 836 no other abnormality was detected in exon 20. No mutations were detected in exons 13, 16, 18 and 19. In adults, mutations were more frequent in acute promyelocitic leukemia and in women. There were no associations between FLT3 mutations and CBC values. Interestingly, FLT3 mutations were less frequently detected in patients whose leukemic cells expressed the CD56 marker. As described for other countries, overall survival was worse in patients with FLT3 mutations. In conclusion, this study demonstrates that the frequency of ITD mutations in FLT3 gene in Brazilian patients with AML was similar to the frequency described in the European and North American populations, whereas activation loop mutations were rarely detected, especially those in D835. Thus, our results suggest that Brazilian patients with AML have a distinct profile of genetic abnormalities. In addition, this is the first study to demonstrate a negative association between FLT3 mutations and the expression of CD56 by leukemic blasts. This is a relevant observation, since CD56 expression per se has been identified as prognostic factor by other investigators. Finally, our study demonstrates that the SSCP method may be useful for screening mutations of FLT3 gene.

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