scholarly journals Promiscuity progression of bioactive compounds over time

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 118 ◽  
Author(s):  
Ye Hu ◽  
Swarit Jasial ◽  
Jürgen Bajorath
Keyword(s):  
Bioactive Compounds ◽  
Time Course ◽  
Massive Data ◽  
Activity Data ◽  
Confidence Levels ◽  
Constant Degree ◽  
Compound Promiscuity ◽  
History Of ◽  
Low Degrees ◽  
Over Time

In the context of polypharmacology, compound promiscuity is rationalized as the ability of small molecules to specifically interact with multiple targets. To study promiscuity progression of bioactive compounds in detail, nearly 1 million compounds and more than 5.2 million activity records were analyzed. Compound sets were assembled by applying different data confidence criteria and selecting compounds with activity histories over many years. On the basis of release dates, compounds and activity records were organized on a time course, which ultimately enabled monitoring data growth and promiscuity progression over nearly 40 years, beginning in 1976. Surprisingly low degrees of promiscuity were consistently detected for all compound sets and there were only small increases in promiscuity over time. In fact, most compounds had a constant degree of promiscuity, including compounds with an activity history of 10 or 20 years. Moreover, during periods of massive data growth, beginning in 2007, promiscuity degrees also remained constant or displayed only minor increases, depending on the activity data confidence levels. Considering high-confidence data, bioactive compounds currently interact with 1.5 targets on average, regardless of their origins, and display essentially constant degrees of promiscuity over time. Taken together, our findings provide expectation values for promiscuity progression and magnitudes among bioactive compounds as activity data further grow.

scholarly journals Analyzing compound activity records and promiscuity degrees in light of publication statistics

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 1227 ◽  
Author(s):  
Ye Hu ◽  
Jürgen Bajorath
Keyword(s):  
Characteristic Feature ◽  
Small Molecules ◽  
Bioactive Compounds ◽  
Scientific Literature ◽  
Multiple Target ◽  
Target Information ◽  
Activity Data ◽  
Publication Statistics ◽  
Compound Promiscuity ◽  
Activity Information

For the generation of contemporary databases of bioactive compounds, activity information is usually extracted from the scientific literature. However, when activity data are analyzed, source publications are typically no longer taken into consideration. Therefore, compound activity data selected from ChEMBL were traced back to thousands of original publications, activity records including compound, assay, and target information were systematically generated, and their distributions across the literature were determined. In addition, publications were categorized on the basis of activity records. Furthermore, compound promiscuity, defined as the ability of small molecules to specifically interact with multiple target proteins, was analyzed in light of publication statistics, thus adding another layer of information to promiscuity assessment. It was shown that the degree of compound promiscuity was not influenced by increasing numbers of source publications. Rather, most non-promiscuous as well as promiscuous compounds, regardless of their degree of promiscuity, originated from single publications, which emerged as a characteristic feature of the medicinal chemistry literature.

scholarly journals Analyzing compound activity records and promiscuity degrees in light of publication statistics

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 1227 ◽  
Author(s):  
Ye Hu ◽  
Jürgen Bajorath
Keyword(s):  
Characteristic Feature ◽  
Small Molecules ◽  
Bioactive Compounds ◽  
Scientific Literature ◽  
Multiple Target ◽  
Target Information ◽  
Activity Data ◽  
Publication Statistics ◽  
Compound Promiscuity ◽  
Activity Information

For the generation of contemporary databases of bioactive compounds, activity information is usually extracted from the scientific literature. However, when activity data are analyzed, source publications are typically no longer taken into consideration. Therefore, compound activity data selected from ChEMBL were traced back to thousands of original publications, activity records including compound, assay, and target information were systematically generated, and their distributions across the literature were determined. In addition, publications were categorized on the basis of activity records. Furthermore, compound promiscuity, defined as the ability of small molecules to specifically interact with multiple target proteins, was analyzed in light of publication statistics, thus adding another layer of information to promiscuity assessment. It was shown that the degree of compound promiscuity was not influenced by increasing numbers of source publications. Rather, most non-promiscuous as well as promiscuous compounds, regardless of their degree of promiscuity, originated from single publications, which emerged as a characteristic feature of the medicinal chemistry literature.

The Path of Standard Albanian Language Formation

2018 ◽  
Vol 5 (2) ◽  
pp. 106-115
Author(s):  
Sindorela Doli Kryeziu
Keyword(s):  
Single Unit ◽  
Cultural Factors ◽  
Language History ◽  
Whole Process ◽  
History Of ◽  
Social And Cultural Factors ◽  
Cultural Body ◽  
Over Time ◽  
Language Literature

Abstract In our paper we will talk about the whole process of standardization of the Albanian language, where it has gone through a long historical route, for almost a century.When talking about standard Albanian language history and according to Albanian language literature, it is often thought that the Albanian language was standardized in the Albanian Language Orthography Congress, held in Tirana in 1972, or after the publication of the Orthographic Rules (which was a project at that time) of 1967 and the decisions of the Linguistic Conference, a conference of great importance that took place in Pristina, in 1968. All of these have influenced chronologically during a very difficult historical journey, until the standardization of the Albanian language.Considering a slightly wider and more complex view than what is often presented in Albanian language literature, we will try to describe the path (history) of the standard Albanian formation under the influence of many historical, political, social and cultural factors that are known in the history of the Albanian people. These factors have contributed to the formation of a common state, which would have, over time, a common standard language.It is fair to think that "all activity in the development of writing and the Albanian language, in the field of standardization and linguistic planning, should be seen as a single unit of Albanian culture, of course with frequent manifestations of specific polycentric organization, either because of divisions within the cultural body itself, or because of the external imposition"(Rexhep Ismajli," In Language and for Language ", Dukagjini, Peja, 1998, pp. 15-18.)

Transocean and the History of Tax Inversions

2018 ◽  
Vol 34 (1) ◽  
pp. 1-12
Author(s):  
Susan M. Albring ◽  
Randal J. Elder ◽  
Mitchell A. Franklin
Keyword(s):  
Multinational Corporations ◽  
Economic Impacts ◽  
Income Taxes ◽  
Tax Rates ◽  
Corporate Tax ◽  
Corporate Income Taxes ◽  
History Of ◽  
Jobs Act ◽  
The U.S ◽  
Over Time

ABSTRACT The first tax inversion in 1983 was followed by small waves of subsequent inversion activity, including two inversions completed by Transocean. Significant media and political attention focused on transactions made by U.S. multinational corporations that were primarily designed to reduce U.S. corporate income taxes. As a result, the U.S. government took several actions to limit inversion activity. The Tax Cuts and Jobs Act of 2017 (TCJA) significantly lowered U.S. corporate tax rates and one expected impact of TCJA is a reduction of inversion activity. Students use the Transocean inversions to understand the reasons why companies complete a tax inversion and how the U.S. tax code affects inversion activity. Students also learn about the structure of inversion transactions and how they have changed over time as the U.S. government attempted to limit them. Students also assess the tax and economic impacts of inversion transactions to evaluate tax policy.

Historical Representations and Recent Changes

2018 ◽  
Author(s):  
Jürgen Schaflechner
Keyword(s):  
Comparative Analysis ◽  
South Asia ◽  
Oral Histories ◽  
Detailed History ◽  
Modern Times ◽  
History Of ◽  
Historical Representations ◽  
The Rich ◽  
Many Sources ◽  
Over Time

Chapter 3 introduces the tradition of ritual journeys and sacred geographies in South Asia, then hones in on a detailed history of the grueling and elaborate pilgrimage attached to the shrine of Hinglaj. Before the construction of the Makran Coastal Highway the journey to the Goddess’s remote abode in the desert of Balochistan frequently presented a lethally dangerous undertaking for her devotees, the hardships of which have been described by many sources in Bengali, Gujarati, Hindi, Sindhi, and Urdu. This chapter draws heavily from original sources, including travelogues and novels, which are supplanted with local oral histories in order to weave a historical tapestry that displays the rich array of practices and beliefs surrounding the pilgrimage and how they have changed over time. The comparative analysis demonstrates how certain motifs, such as austerity (Skt. tapasyā), remain important themes within the whole Hinglaj genre even in modern times while others have been lost in the contemporary era.

Introduction

2018 ◽  
Author(s):  
Marko Geslani
Keyword(s):  
Comparative Study ◽  
Royal Power ◽  
History Of ◽  
Historical Developments ◽  
The Comparative Study ◽  
The Relationship ◽  
Over Time ◽  
Indian Religion

The introduction reviews the historiographic problem of the relation between fire sacrifice (yajña) and image worship (pūjā), which have traditionally been seen as opposing ritual structures serving to undergird the distinction of “Vedic” and “Hindu.” Against such an icono- and theocentric approach, it proposes a history of the priesthood in relation to royal power, centering on the relationship between the royal chaplain (purohita) and astrologer (sāṃvatsara) as a crucial, unexplored development in early Indian religion. In order to capture these historical developments, it outlines a method for the comparative study of ritual forms over time.

The Growth of Historical Method in Tang China

2018 ◽  
Author(s):  
Charles Hartman ◽  
Anthony DeBlasi
Keyword(s):  
Eleventh Century ◽  
Seventh Century ◽  
Daily Production ◽  
Successor State ◽  
Historical Method ◽  
Official History ◽  
History Of ◽  
Over Time

This chapter discusses how the full emergence of the centralized, aristocratic state in the seventh century brought about an official historiography that was part of the bureaucracy of that state. Beginning in the Tang, each dynastic court maintained an office of historiography. Over time, a regularized process evolved that, in theory and often in reality, turned the daily production of court bureaucratic documents into an official history of the dynasty. Although this process was ongoing throughout the dynasty, the final, standard ‘dynastic history’ was usually completed after the dynasty's demise by its successor state. Indeed, the very concept of a series of dynastic histories that, taken together, would present an official history of successive, legitimate Chinese states, dates from the eleventh century.

scholarly journals TIME THROUGH TIME: ITS EVOLUTION THROUGH WESTERN PHILOSOPHY IN SEVEN IDEAS

Think ◽  
2021 ◽  
Vol 20 (58) ◽  
pp. 23-38
Author(s):  
Emily Thomas
Keyword(s):  
Western Philosophy ◽  
The World ◽  
History Of ◽  
Over Time

ABSTRACTWhat is time? Just like everything else in the world, our understanding of time has changed continually over time. This article tracks this question through the history of Western philosophy and looks at major answers from the likes of Aristotle, Kant, and McTaggart.

scholarly journals Acute Stroke Care during the COVID-19 Pandemic: Reduction in the Number of Admissions of Elderly Patients and Increase in Prehospital Delays

2021 ◽  
pp. 1-7
Author(s):  
Gabriel Velilla-Alonso ◽  
Andrés García-Pastor ◽  
Ángela Rodríguez-López ◽  
Ana Gómez-Roldós ◽  
Antonio Sánchez-Soblechero ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Acute Stroke ◽  
Time Course ◽  
Intravenous Thrombolysis ◽  
Stroke Care ◽  
Acute Stroke Care ◽  
Group Data ◽  
Radiological Data ◽  
History Of ◽  
Prehospital Delays

Introduction: We analyzed whether the coronavirus disease 2019 (COVID-19) crisis affected acute stroke care in our center during the first 2 months of lockdown in Spain. Methods: This is a single-center, retrospective study. We collected demographic, clinical, and radiological data; time course; and treatment of patients meeting the stroke unit admission criteria from March 14 to May 14, 2020 (COVID-19 period group). Data were compared with the same period in 2019 (pre-COVID-19 period group). Results: 195 patients were analyzed; 83 in the COVID-19 period group, resulting in a 26% decline of acute strokes and transient ischemic attacks (TIAs) admitted to our center compared with the previous year (p = 0.038). Ten patients (12%) tested positive for PCR SARS-CoV-2. The proportion of patients aged 65 years and over was lower in the COVID-19 period group (53 vs. 68.8%, p = 0.025). During the pandemic period, analyzed patients were more frequently smokers (27.7 vs. 10.7%, p = 0.002) and had less frequently history of prior stroke (13.3 vs. 25%, p = 0.043) or atrial fibrillation (9.6 vs. 25%, p = 0.006). ASPECTS score was lower (9 [7–10] vs. 10 [8–10], p = 0.032), NIHSS score was slightly higher (5 [2–14] vs. 4 [2–8], p = 0.122), onset-to-door time was higher (304 [93–760] vs. 197 [91.25–645] min, p = 0.104), and a lower proportion arrived within 4.5 h from onset of symptoms (43.4 vs. 58%, p = 0.043) during the CO­VID-19 period. There were no differences between proportion of patients receiving recanalization treatment (intravenous thrombolysis and/or mechanical thrombectomy) and in-hospital delays. Conclusion: We observed a reduction in the number of acute strokes and TIAs admitted during the COVID-19 period. This drop affected especially elderly patients, and despite a delay in their arrival to the emergency department, the proportion of patients treated with recanalization therapies was preserved.

Anterior approach levator plication for congenital ptosis, absorpable versus non absorpable sutures

2021 ◽  
pp. 112067212110053
Author(s):  
Moustafa Salamah ◽  
Ashraf Mahrous Eid ◽  
Hani Albialy ◽  
Sherif Sharaf EL Deen
Keyword(s):  
Randomized Study ◽  
Early Postoperative Period ◽  
Polyglactin 910 ◽  
Exclusion Criteria ◽  
Congenital Ptosis ◽  
History Of ◽  
Group A ◽  
Group B ◽  
Over Time

Purpose: To compare the efficacy of two different suture types in levator plication for correction of congenital ptosis. Subjects and methods: Prospective comparative interventional randomized study involving 42 eyes of 42 patients aged more than 6 years with congenital ptosis and good levator action. The exclusion criteria were as follows: bilateral ptosis, history of previous surgery, fair or poor levator action, and associated other ocular diseases. Patients were randomized into group A, in which double-armed 5/0 polyester Ethibond were used, and group B, in which double-armed 5/0 Coated Vicryl® (polyglactin 910) suture material we used. Outcomes including eyelid height and stability of eyelid height over time were compared with follow-up data. The MRD was 4.05 ± 0.36 mm and 3.95 ± 0.34 after 1 week for both groups A and B, respectively. At the end of study follow up period (24 weeks), the MRD was 3.60 ± 0.42 mm in group A, and 2.52 ± 0.85 mm in group B. Conclusion: No difference in eyelid height between two groups in early postoperative period, but the postoperative eyelid height was more stable over time in the 5/0 polyester Ethibond group (group A) than in the 5/0 Coated Vicryl® (polyglactin 910) group (group B).

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