scholarly journals Contraceptive and infertility target DataBase (CITDBase): A contraceptive drug development tool for targeting and analysis of human reproductive specific tissues

2021 ◽  
Author(s):  
Subarna Sinha ◽  
Merrill Knapp ◽  
John Pywtorak ◽  
Greg McCain ◽  
Kenneth Wingerden ◽  
...  
Keyword(s):  
Drug Development ◽  
Development Process ◽  
Target Selection ◽  
Development Tool ◽  
Broad Term ◽  
Human Reproductive ◽  
Selection For ◽  
Biological Entities ◽  
Target Database ◽  
Selection Of

Abstract The long and challenging drug development process begins with discovery biology for the selection of an appropriate target for a specific indication. Target is a broad term that can be applied to a range of biological entities such as proteins, genes and RNAs. Although there are numerous databases available for mining biological entities, publicly available searchable, downloadable databases to aid in target selection for a specific disease or indication (e.g. developing contraceptives and infertility treatments) are limited. We report the development of the Contraceptive Infertility Target DataBase (CITDBase: https://www.citdbase.org), which provides investigators an interface to mine existing transcriptomic and proteomic resources to identify high quality contraceptive/infertility targets. The creation of similar individualized databases is applicable to the identification of targets for other diseases and conditions.

LINGUOCULTURAL POTENTIAL OF EUPHEMISMS-AMULETS

2021 ◽  
pp. 68-74
Author(s):  
SERGEY I. ROMANOV ◽  
Keyword(s):  
Target Selection ◽  
Cultural Factors ◽  
Point Of View ◽  
Negative Consequences ◽  
Cultural Community ◽  
Magical Power ◽  
Selection For ◽  
Cultural Code ◽  
Russian Linguistic ◽  
Selection Of

The article deals with a special type of euphemisms-amulets, that is, linguocultural units endowed with the function of protection. There are two types of euphemisms-amulets from the point of view of relevance: obsolete and current units. Obsolete euphemisms- amulets have targets that are not recognized as dangerous by the modern linguistic and cultural community. Current euphemisms-amulets, although not always consciously, are used by representatives of the modern Russian linguistic and cultural community to protect against something bad. The paper establishes that the use of the euphemism-amulet is based on the transla- tion of the target's representation into another cultural code. The work reveals that the euphemisms-amulets are directed not to mitigate an unwanted nomination but how to replace it. An undesirable nomination is endowed with negative magical properties, which is why the linguocultural community imposes a ban on its use. A protective cultural function is superim- posed on the euphemism. The main pragmatic explanation for the use of the euphemism- amulet is the speaker's desire not to predict an encounter with an unwanted object, which is based on belief in the magical power of the word. The factors that determine the linguocultural specificity of euphemisms-amulets are revealed. The first factor is target selection. For the Russian linguocultural community, such targets include a totemic animal, evil forces representing another world, death. The second factor is the selection of nominations for the euphemistic function, which is determined by culturally marked background knowledge, ideas, and typical practices. The communicative- pragmatic platform for the use of euphemisms-amulets is the belief in the magical power of the word, in the fact that the use of the forbidden word can lead to negative consequences (in particular, to cause the appearance of something dangerous, undesirable). The work proves that the identified cultural factors are universal, based on universal archetypes: one's own / another's, permission / prohibition, life / death. At the same time, the fact of the appearance of the euphemism-amulet, the choice of its internal form is determined by national and cultural factors.

Social Skills for Children: Training Empirically-derived Target Behaviours

1991 ◽  
Vol 8 (4) ◽  
pp. 174-182 ◽  
Author(s):  
Mark D. Weist ◽  
M. Christopher Borden ◽  
Jack W. Finney ◽  
Thomas H. Ollendick
Keyword(s):  
Social Behaviour ◽  
Target Selection ◽  
Role Play ◽  
Interpersonal Problems ◽  
Child Behaviour ◽  
Multiple Baseline ◽  
Selection For ◽  
Play Partner ◽  
Selection Of

We evaluated the empirical validation model of target selection for two boys with interpersonal problems. Behaviours previously identified as distinguishing popular from rejected boys on a role-play measure of social behaviour were targeted for change in these boys who had histories of peer rejection. We trained three of these empirically-derived behaviours — appropriate body orientation, adequate speech intonation, and providing reasons for denying unreasonable requests — in a multiple-baseline-across-behaviours design. On a role-play measure of social behaviour, improvements in the targeted behaviours occurred upon, but not before, introduction of the intervention, confirming the controlling effects of the intervention. Behavioural improvements generalised to untrained role-play scenes and to a novel role-play partner, and were maintained for two of the three behaviours at 4- and 6-month follow-up assessments. The boys also showed improvements in parent-reported child behaviour from pre- to post-training. The study demonstrates use of an empirical approach to the selection of treatment targets for children.

Developing Novel Anticancer Drugs for Targeted Populations: An Update

2020 ◽  
Vol 26 ◽  
Author(s):  
Tadesse Bekele Tafesse ◽  
Mohammed Hussen Bule ◽  
Fazlullah Khan ◽  
Mohammad Abdollahi ◽  
Mohsen Amini
Keyword(s):  
Drug Discovery ◽  
Drug Development ◽  
Anticancer Drugs ◽  
Anticancer Drug ◽  
Development Process ◽  
De Novo ◽  
Drug Repurposing ◽  
Drug Discovery And Development ◽  
Probability Of Success ◽  
Selection Of

Background: Due to higher failure rates, lengthy time and high cost of the traditional de novo drug discovery and development process; the rate of opportunity to get new, safe and efficacious drugs for the targeted population including pediatric patients with cancer becomes sluggish. Objectives: This paper discusses the development of novel anticancer drugs focusing on the identification and selection of target anticancer drug development for the targeted population. Methods: Information presented in this review was obtained from different databases including PUBMED, SCOPUS, Web of Science, and EMBASE. Various keywords were used as search terms. Results: The pharmaceutical companies currently are executing drug repurposing as an alternative means to accelerate the drug development process that reduces the risk of failure, time and cost, which takes 3-12 years with almost 25% overall probability of success as compared to de novo drug discovery and development process (10-17 years) which has less than 10% probability of success. An alternative strategy to the traditional de novo drug discovery and development process, called drug repurposing, is also presented. Conclusion: Therefore, to continue with the progress of developing novel anticancer drugs towards the targeted population, identification and selection of the target to the specific disease type is important considering the aspects of the age of the patient and the disease stages such as each cancer types are different when we consider the disease at a molecular level. Drug repurposing technique becomes an influential alternative strategy to discover and develop novel anticancer drug candidates.

Identifying Measurement Invariant Item Sets in Cross-Cultural Settings Using an Automated Item Selection Procedure

Methodology ◽  
2018 ◽  
Vol 14 (4) ◽  
pp. 177-188 ◽  
Author(s):  
Martin Schultze ◽  
Michael Eid
Keyword(s):  
Measurement Invariance ◽  
Optimal Solution ◽  
Selection Procedure ◽  
Cross Cultural ◽  
Item Selection ◽  
Ant System ◽  
Item Quality ◽  
Ant System Algorithm ◽  
Selection For ◽  
Selection Of

Abstract. In the construction of scales intended for the use in cross-cultural studies, the selection of items needs to be guided not only by traditional criteria of item quality, but has to take information about the measurement invariance of the scale into account. We present an approach to automated item selection which depicts the process as a combinatorial optimization problem and aims at finding a scale which fulfils predefined target criteria – such as measurement invariance across cultures. The search for an optimal solution is performed using an adaptation of the [Formula: see text] Ant System algorithm. The approach is illustrated using an application to item selection for a personality scale assuming measurement invariance across multiple countries.

ESTIMASI NILAI HERITABILITAS BOBOT IKAN MAS VARIETAS PUNTEN DALAM PROGRAM SELEKSI INDIVIDU

2016 ◽  
Vol 11 (3) ◽  
pp. 217
Author(s):  
Estu Nugroho ◽  
Budi Setyono ◽  
Mochammad Su’eb ◽  
Tri Heru Prihadi
Keyword(s):  
Body Weight ◽  
Selection Response ◽  
Base Population ◽  
Breeding Programs ◽  
Male And Female ◽  
Body Weight Trait ◽  
Population Selection ◽  
Selection For ◽  
Weight Trait ◽  
Selection Of

Program pemuliaan ikan mas varietas Punten dilakukan dengan seleksi individu terhadap karakter bobot ikan. Pembentukan populasi dasar untuk kegiatan seleksi dilakukan dengan memijahkan secara massal induk ikan mas yang terdiri atas 20 induk betina dan 21 induk jantan yang dikoleksi dari daerah Punten, Kepanjen (delapan betina dan enam jantan), Kediri (tujuh betina dan 12 jantan), Sragen (27 betina dan 10 jantan), dan Blitar (15 betina dan 11 jantan). Larva umur 10 hari dipelihara selama empat bulan. Selanjutnya dilakukan penjarangan sebesar 50% dan benih dipelihara selama 14 bulan untuk dilakukan seleksi dengan panduan hasil sampling 250 ekor individu setiap populasi. Seleksi terhadap calon induk dilakukan saat umur 18 bulan pada populasi jantan dan betina secara terpisah dengan memilih berdasarkan 10% bobot ikan yang terbaik. Calon induk yang terseleksi kemudian dipelihara hingga matang gonad, kemudian dipilih sebanyak 150 pasang dan dipijahkan secara massal. Didapatkan respons positif dari hasil seleksi berdasarkan bobot ikan, yaitu 49,89 g atau 3,66% (populasi ikan jantan) dan 168,47 g atau 11,43% (populasi ikan betina). Nilai heritabilitas untuk bobot ikan adalah 0,238 (jantan) dan 0,505 (betina).Punten carp breeding programs were carried out by individual selection for body weight trait. The base population for selection activities were conducted by mass breeding of parent consisted of 20 female and 21 male collected from area Punten, eight female and six male (Kepanjen), seven female and 12 male (Kediri), 27 female and 10 male (Sragen), 15 female and 11 male (Blitar). Larvae 10 days old reared for four moths. Then after spacing out 50% of total harvest, the offspring reared for 14 months for selection activity based on the sampling of 250 individual each population. Selection of broodstock candidates performed since 18 months age on male and female populations separately by selecting based on 10% of fish with best body weight. Candidates selected broodstocks were then maintained until mature. In oder to produce the next generation 150 pairs were sets and held for mass spawning. The results revealed that selection response were positive, 49.89 g (3.66%) for male and 168.47 (11.43%) for female. Heritability for body weight is 0.238 (male) and 0.505 (female).

Evaluation of Large-Sunflower Lines of Sunflower on Quantitative Morphological Traits

2020 ◽  
pp. 46-55
Keyword(s):  
Fertility Restoration ◽  
Morphological Characters ◽  
Direct Selection ◽  
Oilseed Crops ◽  
Turkish Origin ◽  
Self Pollination ◽  
Special Area ◽  
Pericarp Color ◽  
Selection For ◽  
Selection Of

Confectionery sunflower - a special area of use of sunflower, which requires the creation of marketable seeds quality features. One of the possible ways to create large-fruited sunflower is to create production hybrids and lines. Objective: to evaluate the created new large-fruited sunflower lines by a complex of morphological characters and determine the best lines for use as large-seeds hybrids as parent components or source material. In 2016-2019 years on the basis of the Institute of Oilseed Crops NAAS a study was conducted to assess the economic characteristics of large-fruited sunflower lines. We studied a collection of 27 lines of large-seeds sources. The lines were created by direct selection or crossing and sampling: Reyny of Argentinean origin, Zaporizhzhya confectionery variety, confectionery hybrid with striped pericarp color of Israeli origin, white seed of Turkish origin, synthetic population - donor of complex resistance. To study from the collection, lines were drawn that went through at least 7 generations with selection for seed size. Experience has shown that the shortest growing season for lines 174d and KP11 was 99 days, and the longest for lines I2K670 was 109 days. In the studied collection, the greatest mass of 1000 seeds has the KP11-146.47g line, which is the mother component and does not have branching. The second by weight of 1000 seeds (109 g) stood out line 168v, which also had branches and pollen fertility restoration genes and will be used as the paternal form. The third largest is also one basket line ZKN51-100. The collection included lines originating from the same combination, but with a different morphotype for the presence and absence of branching. So, based on the combination of KP11 x Zaporizhzhya Confectionery, three lines were obtained. A mass of 1000 seeds was observed in 98-86 g, with the branching line having the largest mass of 1000 seeds. The lines created with one combination VK678 x ZKN32: with a branch 168a had a mass of 1000 seeds 95g, and a line 168b - without a branch 109 g. Of the two lines obtained from the descendants of the combination KP11 x the striped hybrid both had branches, but the seeds were much smaller (weight of 1000 seeds 59 and 79 g). The collection also studied samples created on the basis of varieties and populations 160c, 174, 175b, the mass of 1000 seeds of which turned out to be more acceptable for large-fruited use from 83 to 99 g. Summing up the results of studying the collection of newly created lines, we can highlight the lines 162d, 168v, 175b, KP11 that are potentially promising for use in hybrids. The selections showed that large-fruited lines can be obtained from large-fruited varieties, self-pollination of large-fruited hybrids and crossing lines with hybrids and varieties. Self-pollination and selection of large-fruited lines in several generations does not provide the necessary variability for positive changes in selections. The result of the selection by weight of 1000 seeds in the offspring from crosses and from populations creates opportunities for new large-seeds sunflower.

Intelligent Drug Development

2014 ◽  
Author(s):  
Michael Tansey
Keyword(s):  
Clinical Trials ◽  
Cost Effectiveness ◽  
Drug Development ◽  
Clinical Research ◽  
Development Process ◽  
Drug Development Process ◽  
Individual Trial ◽  
Specific Technology

Clinical research is heavily regulated and involves coordination of numerous pharmaceutical-related disciplines. Each individual trial involves contractual, regulatory, and ethics approval at each site and in each country. Clinical trials have become so complex and government requirements so stringent that researchers often approach trials too cautiously, convinced that the process is bound to be insurmountably complicated and riddled with roadblocks. A step back is needed, an objective examination of the drug development process as a whole, and recommendations made for streamlining the process at all stages. With Intelligent Drug Development, Michael Tansey systematically addresses the key elements that affect the quality, timeliness, and cost-effectiveness of the drug-development process, and identifies steps that can be adjusted and made more efficient. Tansey uses his own experiences conducting clinical trials to create a guide that provides flexible, adaptable ways of implementing the necessary processes of development. Moreover, the processes described in the book are not dependent either on a particular company structure or on any specific technology; thus, Tansey's approach can be implemented at any company, regardless of size. The book includes specific examples that illustrate some of the ways in which the principles can be applied, as well as suggestions for providing a better context in which the changes can be implemented. The protocols for drug development and clinical research have grown increasingly complex in recent years, making Intelligent Drug Development a needed examination of the pharmaceutical process.

Track Segment Association in Target Selection for Interdiction Using a Single Passive Sensor

2021 ◽  
pp. 1-1
Author(s):  
K. Yang ◽  
M. Danino ◽  
Y. Bar-Shalom ◽  
D. Belfadel ◽  
B. Milgrom ◽  
...  
Keyword(s):  
Target Selection ◽  
Track Segment ◽  
Passive Sensor ◽  
Selection For

scholarly journals Regulating the Regulators: Mechanisms of Substrate Selection of the O-GlcNAc Cycling Enzymes OGT and OGA

Glycobiology ◽  
2021 ◽  
Author(s):  
Hannah M Stephen ◽  
Trevor M Adams ◽  
Lance Wells
Keyword(s):  
Nutrient Sensing ◽  
Substrate Selection ◽  
Disease States ◽  
Dynamic Modification ◽  
Selection For ◽  
Outstanding Question ◽  
Glcnac Transferase ◽  
Future Work ◽  
Partner Proteins ◽  
Selection Of

Abstract Thousands of nuclear and cytosolic proteins are modified with a single β-N-acetylglucosamine on serine and threonine residues in mammals, a modification termed O-GlcNAc. This modification is essential for normal development and plays important roles in virtually all intracellular processes. Additionally, O-GlcNAc is involved in many disease states, including cancer, diabetes, and X-linked intellectual disability. Given the myriad of functions of the O-GlcNAc modification, it is therefore somewhat surprising that O-GlcNAc cycling is mediated by only two enzymes: the O-GlcNAc transferase (OGT), which adds O-GlcNAc, and the O-GlcNAcase (OGA), which removes it. A significant outstanding question in the O-GlcNAc field is how do only two enzymes mediate such an abundant and dynamic modification. In this review, we explore the current understanding of mechanisms for substrate selection for the O-GlcNAc cycling enzymes. These mechanisms include direct substrate interaction with specific domains of OGT or OGA, selection of interactors via partner proteins, posttranslational modification of OGT or OGA, nutrient sensing, and localization alteration. Altogether, current research paints a picture of an exquisitely regulated and complex system by which OGT and OGA select substrates. We also make recommendations for future work, toward the goal of identifying interaction mechanisms for specific substrates that may be able to be exploited for various research and medical treatment goals.

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