The Impact of Variable Selection Coverage on Detection of Ligands from a DNA-Encoded Library Screen

2020 ◽  
Vol 25 (5) ◽  
pp. 515-522 ◽  
Author(s):  
Kelly A. McCarthy ◽  
G. Joseph Franklin ◽  
David R. Lancia ◽  
Martin Olbrot ◽  
Eneida Pardo ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Sequencing Data ◽  
Initial Compound ◽  
Single Experiment ◽  
Library Screen ◽  
Drug Discovery Program ◽  
Screening Platform ◽  
The Many ◽  
The Impact ◽  
Entire Picture

DNA-encoded library (DEL) technology has become a prominent screening platform in drug discovery owing to the capacity to screen billions or trillions of compounds in a single experiment. Although numerous successes with DEL technology have been reported, we are unaware of a rigorous examination of the many different variables that can influence a screen’s success. Herein, we explore the impact of variable sample sequencing depth on the detection of tool compounds with known affinities toward a given target while simultaneously probing the effect of initial compound input. Our sequencing data confirm reports that high-affinity compounds can be discovered directly from a DEL screen, but we demonstrate that a mismatch between selection output and sequencing quantity can obscure useful ligands. Our results highlight the importance of selection coverage in grasping the entire picture of a DEL screen where the signal of a weak or underrepresented ligand may be suppressed by the inherent noise of a selection. These potential missed ligands may be critical to the success or failure of a drug discovery program.

Hydrogen Cyanide Polymers from the Impact of Comet P/Shoemaker-Levy 9 on Jupiter

1997 ◽  
Vol 161 ◽  
pp. 179-187
Author(s):  
Clifford N. Matthews ◽  
Rose A. Pesce-Rodriguez ◽  
Shirley A. Liebman
Keyword(s):  
Amino Acids ◽  
Solar System ◽  
Hydrogen Cyanide ◽  
Nitrogen Heterocycles ◽  
Laboratory Studies ◽  
Heterogeneous Solids ◽  
The Many ◽  
Comet Halley ◽  
The Impact ◽  
By Products

AbstractHydrogen cyanide polymers – heterogeneous solids ranging in color from yellow to orange to brown to black – may be among the organic macromolecules most readily formed within the Solar System. The non-volatile black crust of comet Halley, for example, as well as the extensive orangebrown streaks in the atmosphere of Jupiter, might consist largely of such polymers synthesized from HCN formed by photolysis of methane and ammonia, the color observed depending on the concentration of HCN involved. Laboratory studies of these ubiquitous compounds point to the presence of polyamidine structures synthesized directly from hydrogen cyanide. These would be converted by water to polypeptides which can be further hydrolyzed to α-amino acids. Black polymers and multimers with conjugated ladder structures derived from HCN could also be formed and might well be the source of the many nitrogen heterocycles, adenine included, observed after pyrolysis. The dark brown color arising from the impacts of comet P/Shoemaker-Levy 9 on Jupiter might therefore be mainly caused by the presence of HCN polymers, whether originally present, deposited by the impactor or synthesized directly from HCN. Spectroscopic detection of these predicted macromolecules and their hydrolytic and pyrolytic by-products would strengthen significantly the hypothesis that cyanide polymerization is a preferred pathway for prebiotic and extraterrestrial chemistry.

The impact of cultural factors on attachment dynamics: a view from Irish society

2019 ◽  
Vol 13 (2) ◽  
pp. 207-223
Author(s):  
Michael O’Toole
Keyword(s):  
Significant Role ◽  
Emotional Development ◽  
Cultural Factors ◽  
Seamus Heaney ◽  
Irish Society ◽  
Irish Context ◽  
Key Points ◽  
The Many ◽  
The Impact ◽  
The Relationship

In this article I examine aspects of the relationship between mothers and sons from an attachment perspective in an Irish context. Through the works of Irish writers such as Seamus Heaney, John McGahern, and Colm Tóibín, I focus on particular aspects of this relationship, which fails to support the developmental processes of separation and individuation in the many men who come to me for psychotherapy. I illustrate key points concerning this attachment dynamic through the use of clinical examples of my work with two men from my practice. While acknowledging that many other cultural factors play a significant role in the emotional development of children, integrating the work of our poets, novelists, and scholars with an attachment perspective

The unknown acquaintance, or the impact factor and others

2007 ◽  
Vol 148 (4) ◽  
pp. 165-171
Author(s):  
Anna Berhidi ◽  
Edit Csajbók ◽  
Lívia Vasas
Keyword(s):  
Impact Factor ◽  
Citation Analysis ◽  
Index Number ◽  
Scientific Performance ◽  
H Index ◽  
Master List ◽  
The Many ◽  
The Impact

Nobody doubts the importance of the scientific performance’s evaluation. At the same time its way divides the group of experts. The present study mostly deals with the models of citation-analysis based evaluation. The aim of the authors is to present the background of the best known tool – Impact factor – since, according to the authors’ experience, to the many people use without knowing it well. In addition to the „nonofficial impact factor” and Euro-factor, the most promising index-number, h-index is presented. Finally new initiation – Index Copernicus Master List – is delineated, which is suitable to rank journals. Studying different indexes the authors make a proposal and complete the method of long standing for the evaluation of scientific performance.

Surveying adherence of dental clinic patients to preventive measures in oral cavity

2019 ◽  
Vol 24 (2) ◽  
pp. 167-172 ◽  
Author(s):  
T. V. Kudryavtseva ◽  
V. V. Tachalov ◽  
E. S. Loboda ◽  
L. Yu. Orekhova ◽  
E. Yu. Nechai ◽  
...  
Keyword(s):  
Oral Cavity ◽  
Working Conditions ◽  
Oral Hygiene ◽  
Preventive Measures ◽  
Periodontal Diseases ◽  
Dental Health ◽  
Developed Countries ◽  
Dental Clinic ◽  
The Many ◽  
The Impact

Relevance. Periodontal diseases are a medical and social problem due to the wide spread among the population of developed countries and the impact on the quality of life. Among the many factors that are important in the development of inflammatory periodontal diseases, an important role is played by adherence to the recommendations of the dentist in respecting oral hygiene. Aim of the work was to study the adherence of patients of the dental clinic to compliance with preventive measures in the oral cavity.Materials and methods. A total of 98 patients of dental clinic, 62 female (medial age 38,6 ± 14,0 years) and 36 male (medial age 37,2±13,1 years) participated in survey. The study participants flled in the profle and answered questions about age, gender, harmful working conditions and bad habits, frequency of visits to the dental clinic, attitudes to the prevention of dental diseases, knowledge about the means and methods of oral hygiene.Results. As a result of the study, it was found that in the vast majority of cases, respondents are employed in production that does not adversely affect their health (91%), only 8% of patients indicated harmful working conditions.Conclusions. The study revealed that, despite the recommendations of the dentist, patients are not always committed to the implementation of preventive measures in the oral cavity. Dentists need to motivate patients to use not only the usual methods and means of hygiene, but also additional ones necessary for maintaining dental health.

Natural Sesquiterpene Lactones in the Prevention and Treatment of Inflammatory Disorders and cancer: A Systematic Study of this Emerging Therapeutic Approach based on Chemical and Pharmacological Aspect

2020 ◽  
Vol 17 (9) ◽  
pp. 1102-1116
Author(s):  
Sudip Kumar Mandal ◽  
Utsab Debnath ◽  
Amresh Kumar ◽  
Sabu Thomas ◽  
Subhash Chandra Mandal ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Biological Activities ◽  
Sesquiterpene Lactones ◽  
Structural Diversity ◽  
Cancer Drug ◽  
Cancer Drug Discovery ◽  
Anti Cancer ◽  
Drug Discovery Program ◽  
Anti Inflammatory ◽  
Family Based

Background and Introduction: Sesquiterpene lactones are a class of secondary metabolite that contains sesquiterpenoids and lactone ring as pharmacophore moiety. A large group of bioactive secondary metabolites such as phytopharmaceuticals belong to this category. From the Asteraceae family-based medicinal plants, more than 5,000 sesquiterpene lactones have been reported so far. Sesquiterpene lactone-based pharmacophore moieties hold promise for broad-spectrum biological activities against cancer, inflammation, parasitic, bacterial, fungal, viral infection and other functional disorders. Moreover, these moiety based phytocompounds have been highlighted with a new dimension in the natural drug discovery program worldwide after the 2015 Medicine Nobel Prize achieved by the Artemisinin researchers. Objective: These bitter substances often contain an α, β-unsaturated-γ-lactone as a major structural backbone, which in recent studies has been explored to be associated with anti-tumor, cytotoxic, and anti-inflammatory action. Recently, the use of sesquiterpene lactones as phytomedicine has been increased. This study will review the prospect of sesquiterpene lactones against inflammation and cancer. Methods: Hence, we emphasized on the different features of this moiety by incorporating its structural diversity on biological activities to explore structure-activity relationships (SAR) against inflammation and cancer. Results: How the dual mode of action such as anti-inflammatory and anti-cancer has been exhibitedby these phytopharmaceuticals will be forecasted in this study. Furthermore, the correlation of anti-inflammatory and anti-cancer activity executed by the sesquiterpene lactones for fruitful phytotherapy will also be revealed in the present review in the milieu of pharmacophore activity relation and pharmacodynamics study as well. Conclusion: So, these metabolites are paramount in phytopharmacological aspects. The present discussion on the future prospect of this moiety based on the reported literature could be a guide for anti-inflammatory and anti-cancer drug discovery programs for the upcoming researchers.

Individuality and Beyond

2019 ◽  
Author(s):  
Benedetta Zavatta
Keyword(s):  
Moral Autonomy ◽  
First Line ◽  
Philosophical Interpretation ◽  
Individual Personality ◽  
The World ◽  
Regulative Ideal ◽  
Personal Library ◽  
The Many ◽  
The Individual ◽  
The Impact

Based on an analysis of the marginal markings and annotations Nietzsche made to the works of Emerson in his personal library, the book offers a philosophical interpretation of the impact on Nietzsche’s thought of his reading of these works, a reading that began when he was a schoolboy and extended to the final years of his conscious life. The many ideas and sources of inspiration that Nietzsche drew from Emerson can be organized in terms of two main lines of thought. The first line leads in the direction of the development of the individual personality, that is, the achievement of critical thinking, moral autonomy, and original self-expression. The second line of thought is the overcoming of individuality: that is to say, the need to transcend one’s own individual—and thus by definition limited—view of the world by continually confronting and engaging with visions different from one’s own and by putting into question and debating one’s own values and certainties. The image of the strong personality that Nietzsche forms thanks to his reading of Emerson ultimately takes on the appearance of a nomadic subject who is continually passing out of themselves—that is to say, abandoning their own positions and convictions—so as to undergo a constant process of evolution. In other words, the formation of the individual personality takes on the form of a regulative ideal: a goal that can never be said to have been definitively and once and for all attained.

Textual Transformations

2019 ◽  
Keyword(s):  
Early Modern ◽  
Financial Incentives ◽  
Book History ◽  
John Dryden ◽  
Book Production ◽  
Original Essays ◽  
Wide Range ◽  
Lucy Hutchinson ◽  
The Many ◽  
The Impact

This collection of twelve original essays by an international team of eminent scholars in the field of book history explores the many ways in which early modern books were subject to reworking, re-presentation, revision and reinterpretation. Their history is often the history of multiple, sometimes competing, agencies as their texts were re-packaged, redirected and transformed in ways that their original authors might hardly recognize. The essays discuss the processes of editing, revision, redaction, selection, abridgement, glossing, disputation, translation and posthumous publication that resulted in a textual elasticity and mobility that could dissolve distinctions between text and paratexts, textuality and intertextuality, manuscript and print, author and reader or editor, such that title and author’s name are no longer sufficient pointers to a book’s identity or contents. The essays are alive to the impact of commercial and technological aspects of book production and distribution (discussing, for example, the career of the pre-eminent bookseller John Nourse, the market appeal of abridgements, and the financial incentives to posthumous publication), but their interest is also in the many additional forms of agency that shaped texts and their meanings as books were repurposed to articulate, and respond to, a variety of cultural and individual needs. They engage with early modern religious, political, philosophical and scholarly trends and debates as they discuss a wide range of genres and kinds of publication (including fictional and non-fictional prose, verse miscellanies, abridgements, sermons, religious controversy) and of authors and booksellers (including Lucy Hutchinson, Richard Baxter, Thomas Burnet, Elizabeth Rowe, John Dryden, and Samuel Taylor Coleridge, Lucy Hutchinson, Henry Maundrell, John Nourse; Jonathan Swift, Samuel Richardson, John Tillotson, Isaac Watts and John Wesley).

scholarly journals Changing landscapes: Gay men in the west and northwest of Ireland

Sexualities ◽  
2020 ◽  
pp. 136346072098169
Author(s):  
Aidan McKearney
Keyword(s):  
Gay Men ◽  
Social Rights ◽  
Irish Society ◽  
Recent Past ◽  
Same Sex ◽  
Lgbt People ◽  
The Many ◽  
Northwest Region ◽  
The Impact ◽  
Insight Into

This article focuses on the experiences of gay men in the rural west and northwest region of Ireland, during a period of transformational social and political change in Irish society. These changes have helped facilitate new forms of LGBTQI visibility, and local radicalism in the region. Same-sex weddings, establishment of rural LGBT groups and marching under an LGBT banner at St Patricks Day parades would have been unthinkable in the recent past; but they are now becoming a reality. The men report continuing challenges in their lives as gay men in the nonmetropolitan space, but the emergence of new visibility, voice and cultural acceptance of LGBT people is helping change their lived experiences. The study demonstrates the impact of local activist LGBT citizens. Through their testimonies we can gain an insight into the many, varied and interwoven factors that have interplayed to create the conditions necessary for the men to: increasingly define themselves as gay to greater numbers of people in their localities; to embrace greater visibility and eschew strategies of silence; and aspire to a host of legal, political, cultural and social rights including same-sex marriage. Organic forms of visibility and local radicalism have emerged in the region and through an analysis of their testimonies we can see how the men continue to be transformed by an ever-changing landscape.

scholarly journals miR-208b Reduces the Expression of Kcnj5 in a Cardiomyocyte Cell Line

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 719
Author(s):  
Julia Hupfeld ◽  
Maximilian Ernst ◽  
Maria Knyrim ◽  
Stephanie Binas ◽  
Udo Kloeckner ◽  
...  
Keyword(s):  
Untranslated Region ◽  
Electrical Remodeling ◽  
Sequencing Data ◽  
Western Blots ◽  
Cardiovascular Pathology ◽  
Hypertrophic Response ◽  
Channel Dependent ◽  
Cardiac Excitation ◽  
The Impact ◽  
Generation Sequencing

MicroRNAs (miRs) contribute to different aspects of cardiovascular pathology, among them cardiac hypertrophy and atrial fibrillation. Cardiac miR expression was analyzed in a mouse model with structural and electrical remodeling. Next-generation sequencing revealed that miR-208b-3p was ~25-fold upregulated. Therefore, the aim of our study was to evaluate the impact of miR-208b on cardiac protein expression. First, an undirected approach comparing whole RNA sequencing data to miR-walk 2.0 miR-208b 3′-UTR targets revealed 58 potential targets of miR-208b being regulated. We were able to show that miR-208b mimics bind to the 3′ untranslated region (UTR) of voltage-gated calcium channel subunit alpha1 C and Kcnj5, two predicted targets of miR-208b. Additionally, we demonstrated that miR-208b mimics reduce GIRK1/4 channel-dependent thallium ion flux in HL-1 cells. In a second undirected approach we performed mass spectrometry to identify the potential targets of miR-208b. We identified 40 potential targets by comparison to miR-walk 2.0 3′-UTR, 5′-UTR and CDS targets. Among those targets, Rock2 and Ran were upregulated in Western blots of HL-1 cells by miR-208b mimics. In summary, miR-208b targets the mRNAs of proteins involved in the generation of cardiac excitation and propagation, as well as of proteins involved in RNA translocation (Ran) and cardiac hypertrophic response (Rock2).

scholarly journals The ground-level ozone concentration is inversely correlated with the number of COVID-19 cases in Warsaw, Poland

2021 ◽  
Author(s):  
Oskar Wiśniewski ◽  
Wiesław Kozak ◽  
Maciej Wiśniewski
Keyword(s):  
Wind Speed ◽  
Ozone Concentration ◽  
Inverse Correlation ◽  
Ground Level ◽  
Viral Agent ◽  
The Novel ◽  
Weather Factors ◽  
Ground Level Ozone ◽  
The Many ◽  
The Impact

AbstractCOVID-19, which is a consequence of infection with the novel viral agent SARS-CoV-2, first identified in China (Hubei Province), has been declared a pandemic by the WHO. As of September 10, 2020, over 70,000 cases and over 2000 deaths have been recorded in Poland. Of the many factors contributing to the level of transmission of the virus, the weather appears to be significant. In this work, we analyze the impact of weather factors such as temperature, relative humidity, wind speed, and ground-level ozone concentration on the number of COVID-19 cases in Warsaw, Poland. The obtained results show an inverse correlation between ground-level ozone concentration and the daily number of COVID-19 cases.

Sign in / Sign up

Export Citation Format

Share Document