scholarly journals Review of Present Trends and Future Scope of Pharmacogenomics in Drug Discovery and Development Process

2020 ◽  
Vol 13 (1) ◽  
pp. 66-78
Author(s):  
V. Chandrakala ◽  
Utpal Kumar Sanki
Keyword(s):  
Ethical Issues ◽  
Clinical Trial Design ◽  
Dna Polymorphisms ◽  
Receptor Protein ◽  
Computer Assisted ◽  
Protein Chemistry ◽  
The Difference ◽  
Small Change ◽  
The Stability ◽  
The Individual

Pharmacogenomics combines traditional pharmaceutical sciences such as biochemistry with annotated knowledge of genetics, protein chemistry, and DNA polymorphisms. The difference of therapeutic efficacy of the same drug in different individual can be best explained by the study of genetic polymorphisms that underlie individual differences in drug response. The small change of the genome in one individual may make a drug inefficacious as oppose to the other patients. Such variability will bring the individualization of the therapy to obtain the best effects of the drug, as an example autologous dendrimer got a tremendous success in the cancer therapy of the individual. Markers of exposure can determine whether the desired target tissues of a subject have been exposed to a drug at physiological concentrations. Gene expression profiling is a tool that can be used to characterize chemically induced toxicity in cells and/or animal models, in order to provide plausible explanations for observed toxicity in preclinical testing. Pharmacogenomics holds the promise that drugs might one day in future be tailor-made for individuals and adapted to each person's own genetic makeup by the use of microarray technology to express the gene which in turn helps to develop receptor protein. The stability of the drug and its toxicity can be predicted prior to administration of the drug to the subject through the knowledge of computer assisted structural simulation and DNA reactivity technology respectively. This article provides some critical aspects of drug developments, clinical trial design and ethical issues which are centered with pharmacogenomics.

Complexation of Cobalt(II), Nickel(II), and Copper(II) Ions with Pyridine, 2-Methylpyridine, 3-Methylpyridine, and 4-Methylpyridine in Acetonitrile

2000 ◽  
Vol 55 (3-4) ◽  
pp. 277-284 ◽  
Author(s):  
Makoto Kurihara ◽  
Takuji Kawashima ◽  
Kazuhiko Ozutsumi
Keyword(s):  
Electronic Spectra ◽  
Thermodynamic Data ◽  
The Other ◽  
Thermodynamic Quantities ◽  
Free Energies ◽  
Octahedral Structure ◽  
Spectrophotometric Data ◽  
The Difference ◽  
The Stability ◽  
The Individual

Abstract Thermodynamic data of the complexation of cobalt(II), nickel(II), and copper(II) ions with pyridine (py), 2-methylpyridine (2Me-py), 3-methylpyridine (3Me-py), and 4-methylpyridine (4Me-py) have been determined by calorimetry and spectrophotometry in acetonitrile (MeCN) containing 0.1 mol dm-3 (C2H5)4NClO4 as a constant ionic medium at 25 °C. The calorimetric and spectrophotometric data for py, 3Me-py, and 4Me-py revealed the formation of [ML]2+, [ML2]2+, [ML3]2+, and [ML4]2+ (M = Co2+, Ni2+, Cu2+; L = py, SMe-py, 4Me-py). For 2Me-py, on the other hand, the formation of only one complex, [M(2Me-py)]2+ (M = Co2+, Ni2+), was detected. The stepwise thermodynamic quantities and the individual electronic spectra of the complexes suggest that all of these have a six-coordinate octahedral structure. The stability of the [M(2Me-py)]2+ (M = Co2+, Ni2+) complexes is much lower than that of the corresponding py, 3Me-py, and 4Me-py complexes. The difference in the stability of the 2Me-py complexes is mainly due to their unfavorable entropy changes because the differences of enthalpies for all the complexes are not so significant. The free energies for the formation of the mono complexes follow the order Mn(II) > Co(II) > Ni(II) > Cu(II) < Zn(II) for the py, 3Me-py, and 4Me-py systems. The ΔH°1 values vary in the same order and the ΔS°1 values are similar. Hence, the stability difference of the mono complexes originates from the enthalpic term

Über Actin-Nucleotide und die Funktion und Bindung der Nucleotidphosphate im G- und F-Actin

1961 ◽  
Vol 16 (7) ◽  
pp. 435-444 ◽  
Author(s):  
N. Grubhofer ◽  
Hans H. Weber
Keyword(s):  
Half Life ◽  
Equilibrium Concentration ◽  
Special Kind ◽  
The Other ◽  
Mechanical Destruction ◽  
Reversible Dissociation ◽  
First Case ◽  
The Difference ◽  
The Stability ◽  
The Individual

1. If pure F-actin-ADP * which is free of enzymes is depolymerized G-actin-ATP * arises in the presence of 10-4 M ATP, G-actin-ITP * in the presence of 10-4 M ITP, and G-actin-ADP in the presence of 10-4 M ADP. If the depolymerization takes place in the absence of free nucleotide phosphate G-actin-ADP also arises. If G-actin-ADP is added to a solution containing 10-4 M ITP or ATP the bound ADP is exchanged with ATP respectively with ITP (Section II).2. G-actin-ATP and G-actin-ITP polymerize to F-actin-ADP and to F-actin-IDP respectively by splitting off the γ-phosphate of the ATP or ITP. G-actin-ADP polymerizes to F-actin-ADP without splitting off phosphate. The polymerization of G-actin-ADP is as complete as the polymerization of G-actin-ATP; but the process is perceptibly shower (Section II).3. G-actin that is not bound to a nucleotide phosphate does not polymerize (Section II).4. G-actin-ADP in the absence of free ADP spontaneously disintegrates in a half-life of 70 minutes to yield G-actin and ADP. If the dissociating ADP is continuously removed by being bound to Dowex 1 × 10 the half life drops to 7 to 8 minutes. In the presence of Dowex G-actin-ATP disintegrates in a half life of 240 minutes (Section III).5. The disintegration of G-actin-ADP takes place in two stages. A reversible dissociation into ADP and G-actin I is followed by an irreversible denaturation of G-actin I to G-actin II in a half life ~ 12 minutes. Contrary to actin I G-actin II even on the addition of ATP no longer polymerizes. The difference in the half life of pure G-actin-ADP on the hand and of G-actin-ADP+ADP as well as G-actin-ATP on the other must be attributed to the relatively high equilibrium concentration of G-actin I in the first case and of the relatively slight equilibrium concentration of G-actin I in the second case (Section IV).6. If the alkaline earth of G-actin is blocked by 10-3 M EDTA G-actin-ATP disintegrates in a half life ∼ 3 minutes and G-actin-ADP in a half life ∼ 0,3 minutes. On the other hand, the stability of F-actin-ADP is not noticeably affected (Section V).7. Through a two hour rapid dialysis in the presence of 10-4 M ATP the KCl-content of an F-actin-ADP solution drops to 5 × 10-4 M KCl. In spite of this the depolymerization and exchange of ADP with ATP is finished not before 40 hours if the solution remains at rest. If, however, the actin solution containing 5 × 10-4 M KCl is treated with the Teflon homogenizer for about 30 sec. depolymerization and ADP-ATP-exchange occur immediately. On the contrary, F-actin-ADP in 10–1 M KCl solution is not affected at all by a treatment with the Teflon-homogenizer. Apparently the decrease of the KClconcentration from 10-1 M to 5 × 10-4 M considerably diminishes the strength of the bond between the actin monomers without immediately destroying the F-actin arrangement. The immediate ADP-ATP-exchange after the mechanical destruction of the F-actin arrangement proves that this exchange in F-actin does not take place only because of steric hindrance. ADP is present in F-actin apparently between the individual monomers so that EDTA, ATP and enzymes affecting ATP cannot approach ADP. Consequently it is not necessary to assume that the extraordinary stability of F-actin-ADP is due to a special kind of bond between actin monomers and nucleotide phosphate (Section V).8. In the appendix it is shown that G-actin-ADP does not polymerize 15′ after preparation if the aceton dried muscle powder is prepared at pH 8 to 9 instead of pH ∼ 7.

Implications of Person Fluctuation for the Stability and Validity of Test Scores

Methodology ◽  
2006 ◽  
Vol 2 (4) ◽  
pp. 142-148 ◽  
Author(s):  
Pere J. Ferrando
Keyword(s):  
Item Response ◽  
Test Scores ◽  
Temporal Stability ◽  
Person Fit ◽  
Item Parameters ◽  
Individual Trait ◽  
The Stability ◽  
The Individual ◽  
Different Levels ◽  
Fluctuation Model

In the IRT person-fluctuation model, the individual trait levels fluctuate within a single test administration whereas the items have fixed locations. This article studies the relations between the person and item parameters of this model and two central properties of item and test scores: temporal stability and external validity. For temporal stability, formulas are derived for predicting and interpreting item response changes in a test-retest situation on the basis of the individual fluctuations. As for validity, formulas are derived for obtaining disattenuated estimates and for predicting changes in validity in groups with different levels of fluctuation. These latter formulas are related to previous research in the person-fit domain. The results obtained and the relations discussed are illustrated with an empirical example.

Use of a Lyophilized Reference Plasma to Compare Coagulation Test Procedures

1975 ◽  
Vol 34 (02) ◽  
pp. 426-444 ◽  
Author(s):  
J Kahan ◽  
I Nohén
Keyword(s):  
Oral Anticoagulant Therapy ◽  
Repeated Measurements ◽  
Test Procedures ◽  
Coagulation Activity ◽  
Close Relationship ◽  
Measured Activity ◽  
Test Materials ◽  
The Difference ◽  
The Stability ◽  
The One

SummaryIn 4 collaborative trials, involving a varying number of hospital laboratories in the Stockholm area, the coagulation activity of different test materials was estimated with the one-stage prothrombin tests routinely used in the laboratories, viz. Normotest, Simplastin-A and Thrombotest. The test materials included different batches of a lyophilized reference plasma, deep-frozen specimens of diluted and undiluted normal plasmas, and fresh and deep-frozen specimens from patients on long-term oral anticoagulant therapy.Although a close relationship was found between different methods, Simplastin-A gave consistently lower values than Normotest, the difference being proportional to the estimated activity. The discrepancy was of about the same magnitude on all the test materials, and was probably due to a divergence between the manufacturers’ procedures used to set “normal percentage activity”, as well as to a varying ratio of measured activity to plasma concentration. The extent of discrepancy may vary with the batch-to-batch variation of thromboplastin reagents.The close agreement between results obtained on different test materials suggests that the investigated reference plasma could be used to calibrate the examined thromboplastin reagents, and to compare the degree of hypocoagulability estimated by the examined PIVKA-insensitive thromboplastin reagents.The assigned coagulation activity of different batches of the reference plasma agreed closely with experimentally obtained values. The stability of supplied batches was satisfactory as judged from the reproducibility of repeated measurements. The variability of test procedures was approximately the same on different test materials.

Empirical Study On Attributes Leading To Satisfaction Among Bank Customer

2019 ◽  
Vol 118 (7) ◽  
pp. 101-110
Author(s):  
Ms.U.Sakthi Veeralakshmi ◽  
Dr.G. Venkatesan
Keyword(s):  
Service Quality ◽  
Behavioral Intention ◽  
Banking Sector ◽  
Positive Impact ◽  
Quality Performance ◽  
Public And Private ◽  
The Difference ◽  
The Individual ◽  
Private Banking ◽  
Service Gap

This research aims at measuring the service quality in public and private banking sector and identifying its relationship to customer satisfaction and behavioral intention. The study was conducted among 500 bank customers by using revised SERVQUAL instrument with 26 items. Behavioral intention of the customers was measured by using the behavioral intention battery. The researcher has used a seven point likert scaling to measure the expected and perceived service quality (performance) and the behavioral intention of the customer. The instrument was selected as the most reliable device to measure the difference-score conceptualization. It is used to evaluate service gap between expectation and perception of service quality. Modifications are made on the SERVQUAL instrument to make it specific to the Banking sector. Questions were added to the instrument like Seating space for waiting (Tangibility), Parking space in the Bank (Tangibility), Variety of products / schemes available (Tangibility), Banks sincere steps to handling Grievances of the customers (Responsiveness). The findings of the study revealed that the customer’s perception (performance) is lower than expectation of the service quality rendered by banks. Responsiveness and Assurance SQ dimensions were the most important dimensions in service quality scored less SQ gap. The study concluded that the individual service quality dimensions have a positive impact on Overall Satisfaction.

THE SUBJECT FIELD OF INSTITUTIONAL EDUCATION: THE SENSE AND PROSPECTS OF DEVELOPMENT IN UKRAINE

2020 ◽  
pp. 25-38
Author(s):  
Irina Mordous
Keyword(s):  
Decisive Role ◽  
Subject Field ◽  
National Education ◽  
Progressive Development ◽  
Separate Area ◽  
Economic Transformations ◽  
The Difference ◽  
The Individual ◽  
Political Economic

The development of modern civilization attests to its decisive role in the progressive development of institutions. They identified the difference between Western civilization and the rest of the world. Confirmation of the institutional advantages of the West was its early industrialization. The genesis and formation of institutionalism in its ideological and conceptualmethodological orientation occurs as a process alternative to neoclassic in the context of world heterodoxia, which quickly spread in social science. Highlighting institutional education as a separate area of sociocultural activity is determined by the factor of differentiation of institutional theory as a whole. A feature of institutional education is its orientation toward the individual and his/her transformation into a personality. The content of institutional education is revealed through the analysis of the institution, which includes a set of established customs, traditions, ways of thinking, behavioral stereotypes of individuals and social groups. The dynamics of socio-political, economic transformations in Ukraine requires a review of the foundations of national education and determination of the prospects for its development in the 21st century in the context of institutionalism.

Quantitative indicators of air traffic controllers’ attitude to the danger of errors

2020 ◽  
pp. 68-78
Author(s):  
O. M. Reva ◽  
V. V. Kamyshin ◽  
S. P. Borsuk ◽  
V. A. Shulhin ◽  
A. V. Nevynitsyn
Keyword(s):  
Human Factor ◽  
Differential Method ◽  
Air Traffic ◽  
Professional Activity ◽  
Aviation Accidents ◽  
Air Traffic Controllers ◽  
The Difference ◽  
Level Of Significance ◽  
The Individual ◽  
High Level

The negative and persistent impact of the human factor on the statistics of aviation accidents and serious incidents makes proactive studies of the attitude of “front line” aviation operators (air traffic controllers, flight crewmembers) to dangerous actions or professional conditions as a key component of the current paradigm of ICAO safety concept. This “attitude” is determined through the indicators of the influence of the human factor on decision-making, which also include the systems of preferences of air traffic controllers on the indicators and characteristics of professional activity, illustrating both the individual perception of potential risks and dangers, and the peculiarities of generalized group thinking that have developed in a particular society. Preference systems are an ordered (ranked) series of n = 21 errors: from the most dangerous to the least dangerous and characterize only the danger preference of one error over another. The degree of this preference is determined only by the difference in the ranks of the errors and does not answer the question of how much time one error is more dangerous in relation to another. The differential method for identifying the comparative danger of errors, as well as the multistep technology for identifying and filtering out marginal opinions were applied. From the initial sample of m = 37 professional air traffic controllers, two subgroups mB=20 and mG=7 people were identified with statisti-cally significant at a high level of significance within the group consistency of opinions a = 1%. Nonpara-metric optimization of the corresponding group preference systems resulted in Kemeny’s medians, in which the related (middle) ranks were missing. Based on these medians, weighted coefficients of error hazards were determined by the mathematical prioritization method. It is substantiated that with the ac-cepted accuracy of calculations, the results obtained at the second iteration of this method are more ac-ceptable. The values of the error hazard coefficients, together with their ranks established in the preference systems, allow a more complete quantitative and qualitative analysis of the attitude of both individual air traffic controllers and their professional groups to hazardous actions or conditions.

In the stability of paints and varnishes for protective and decorative wood finish

2016 ◽  
Author(s):  
Ю.И. Цой
Keyword(s):  
Organic Solvents ◽  
Evaluation Criteria ◽  
Ternary Systems ◽  
Solubility Parameters ◽  
Formaldehyde Resin ◽  
Film Forming ◽  
The Difference ◽  
Molecular Forces ◽  
The Stability ◽  
Thermodynamic Interaction

Задача получения однородного состава ЛКМ сводится к правильному выбору пленкообразователей и соответствующих растворителей и, в случае необходимости, разбавителей и добавок. На основе положений теории растворимости была проведена оценка совместимости компонентов и стабильности таких систем. Критериями оценки были приняты параметры растворимости и термодинамического взаимодействия. Исследовали совместимость алкидных лаков с аминоформальдегидными смолами в бутаноле, и результаты этих исследований представлены в треугольной фазовой диаграмме. Для оценки совместимости смол по результатам расчета параметров термодинамического взаимодействия были построены спинодали для тройных систем. Как показывает анализ результатов проведенных исследований, даже при большой разности ?? = |?12 – ?13| = 0,2 наблюдается небольшая область несовместимости. С уменьшением разности ?? область несовместимости сужается. При ?23 > ?с область несовместимости расширяется как для ? = 0,2, так и для ?? = 0,1 и ?? = 0. Таким образом, для таких систем на совместимость компонентов, в первую очередь, влияет их взаимодействие между собой – чем оно больше, тем лучше они совместимы. Проведенные исследования показали, что парциальные параметры растворимости, учитывающие природу когезионных сил, более объективно характеризуют растворимость пленкообразующих смол в органических растворителях, чем их общий параметр растворимости. Растворимость пленкообразующих алкидных и этерифицированных аминоформальдегидных смол в органических растворителях обусловлена термодинамическим взаимодействием молекулярных сил различной природы. Стабильность смеси алкидной и этерифицированной аминоформальдегидной смолы в бутаноле обусловлена в большей степени термодинамическим взаимодействием молекулярных сил; при этом степень бутанолизации меламиноформальдегидной смолы оказывает наибольшее влияние на стабильность cистемы. Проведенные исследования по стабильности лакокрасочных смесей из различных пленкообразующих смол на основе рассмотренных критериев оценки могут быть использованы для совершенствования технологии защитно-декоративной отделки древесины. The problem of obtaining a homogeneous composition of the coatings is reduced to the proper selection of film-forming agents, and diluent and, if appropriate, diluents and additives. On the basis of the theory of solubility, we have carried out the assessment of the compatibility of the components and stability of such systems. The evaluation criteria were adopted the parameters of the solubility and thermodynamic interaction. Researched the compatibility with alkyd varnishes aminoformaldehyde resin in butanol, and the results of these studies are presented in the triangular phase diagram. To evaluate the compatibility of the resins according to the results of calculation of thermodynamic parameters of interaction were built spinodal for ternary systems. As the analysis of the results of the studies, even when the difference ??|?12 – ?13| = 0,2 there is a small area of incompatibility. With the decrease of the difference ? ? region incompatibility narrows. When ?23> ?с region incompatibility extends to ?? = 0,2, and for ?? = 0.1 and ?? = 0. Thus, for such systems, compatibility of components, primarily, affects their interaction with each other – the further away it is, the better they are compatible. Studies have shown that the partial solubility parameters, which take into account the nature of cohesive forces, more objectively characterize the solubility of film-forming resins in organic solvents than their total solubility parameter. The solubility and film-forming aminoformaldehyde esterified alkyd resins in organic solvents due to thermodynamic interaction of molecular forces of different nature. Тhe stability of the mixture and aminoformaldehyde esterified alkyd resin in butanol is generated largely by thermodynamic forces of molecular interaction; the degree of butanolate melamine-formaldehyde resin has the greatest effect on the stability of the system. Conducted research on the stability of the paint mixtures of various film-forming resins on the basis of the evaluation criteria can be used to improve the technology of protective and decorative wood finish.

Natural Products: Experimental Efficient Agents for Inflammatory Bowel Disease Therapy

2020 ◽  
Vol 25 (46) ◽  
pp. 4893-4913 ◽  
Author(s):  
Fan Cao ◽  
Jie Liu ◽  
Bing-Xian Sha ◽  
Hai-Feng Pan
Keyword(s):  
Inflammatory Bowel Disease ◽  
Natural Products ◽  
Immune System ◽  
Bowel Disease ◽  
Therapeutic Potential ◽  
Adaptive Immune System ◽  
Receptor Protein ◽  
Intestinal Epithelia ◽  
Inflammatory Bowel ◽  
The Individual

: Inflammatory bowel disease (IBD) is a chronic, elusive disorder resulting in relapsing inflammation of intestine with incompletely elucidated etiology, whose two representative forms are ulcerative colitis (UC) and Crohn’s disease (CD). Accumulating researches have revealed that the individual genetic susceptibility, environmental risk elements, intestinal microbial flora, as well as innate and adaptive immune system are implicated in the pathogenesis and development of IBD. Despite remarkable progression of IBD therapy has been achieved by chemical drugs and biological therapies such as aminosalicylates, corticosteroids, antibiotics, anti-tumor necrosis factor (TNF)-α, anti-integrin agents, etc., healing outcome still cannot be obtained, along with inevitable side effects. Consequently, a variety of researches have focused on exploring new therapies, and found that natural products (NPs) isolated from herbs or plants may serve as promising therapeutic agents for IBD through antiinflammatory, anti-oxidant, anti-fibrotic and anti-apoptotic effects, which implicates the modulation on nucleotide- binding domain (NOD) like receptor protein (NLRP) 3 inflammasome, gut microbiota, intestinal microvascular endothelial cells, intestinal epithelia, immune system, etc. In the present review, we will summarize the research development of IBD pathogenesis and current mainstream therapy, as well as the therapeutic potential and intrinsic mechanisms of NPs in IBD.

Quality-of-Life Measurement in Advanced Cancer: Assessing the Individual

1999 ◽  
Vol 17 (11) ◽  
pp. 3603-3611 ◽  
Author(s):  
Dympna Waldron ◽  
Ciaran A. O'Boyle ◽  
Michael Kearney ◽  
Michael Moriarty ◽  
Desmond Carney
Keyword(s):  
Quality Of Life ◽  
Advanced Cancer ◽  
Internal Validity ◽  
Semistructured Interview ◽  
Incurable Cancer ◽  
Life Measurement ◽  
The Difference ◽  
The Individual ◽  
Very High

PURPOSE: Despite the increasing importance of assessing quality of life (QoL) in patients with advanced cancer, relatively little is known about individual patient's perceptions of the issues contributing to their QoL. The Schedule for the Evaluation of Individual Quality of Life (SEIQoL) and the shorter SEIQoL–Direct Weighting (SEIQoL-DW) assess individualized QoL using a semistructured interview technique. Here we report findings from the first administration of the SEIQoL and SEIQoL-DW to patients with advanced incurable cancer. PATIENTS AND METHODS: QoL was assessed on a single occasion using the SEIQoL and SEIQoL-DW in 80 patients with advanced incurable cancer. RESULTS: All patients were able to complete the SEIQoL-DW, and 78% completed the SEIQoL. Of a possible score of 100, the median QoL global score was as follows: SEIQoL, 61 (range, 24 to 94); SEIQoL-DW, 60.5 (range, 6 to 95). Psychometric data for SEIQoL indicated very high levels of internal consistency (median r = .90) and internal validity (median R2 = 0.88). Patients' judgments of their QoL were unique to the individual. Family concerns were almost universally rated as more important than health, the difference being significant when measured using the SEIQoL-DW (P = .002). CONCLUSION: Patients with advanced incurable cancer were very good judges of their QoL, and many patients rated their QoL as good. Judgments were highly individual, with very high levels of consistency and validity. The primacy given to health in many QoL questionnaires may be questioned in this population. The implications of these findings are discussed with regard to clinical assessment and advance directives.

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