scholarly journals Regioselective N-alkylation of the 1H-indazole scaffold; ring substituent and N-alkylating reagent effects on regioisomeric distribution

2021 ◽  
Vol 17 ◽  
pp. 1939-1951
Author(s):  
Ryan M Alam ◽  
John J Keating
Keyword(s):  
Alkyl Halide ◽  
Sodium Hydride ◽  
Product Yield ◽  
Efficient Synthesis ◽  
Initial Screening ◽  
Electronic Effects ◽  
Therapeutic Drugs ◽  
Alkylating Reagents ◽  
High Degree ◽  
The Impact

The indazole scaffold represents a promising pharmacophore, commonly incorporated in a variety of therapeutic drugs. Although indazole-containing drugs are frequently marketed as the corresponding N-alkyl 1H- or 2H-indazole derivative, the efficient synthesis and isolation of the desired N-1 or N-2 alkylindazole regioisomer can often be challenging and adversely affect product yield. Thus, as part of a broader study focusing on the synthesis of bioactive indazole derivatives, we aimed to develop a regioselective protocol for the synthesis of N-1 alkylindazoles. Initial screening of various conditions revealed that the combination of sodium hydride (NaH) in tetrahydrofuran (THF) (in the presence of an alkyl bromide), represented a promising system for N-1 selective indazole alkylation. For example, among fourteen C-3 substituted indazoles examined, we observed > 99% N-1 regioselectivity for 3-carboxymethyl, 3-tert-butyl, 3-COMe, and 3-carboxamide indazoles. Further extension of this optimized (NaH in THF) protocol to various C-3, -4, -5, -6, and -7 substituted indazoles has highlighted the impact of steric and electronic effects on N-1/N-2 regioisomeric distribution. For example, employing C-7 NO2 or CO2Me substituted indazoles conferred excellent N-2 regioselectivity (≥ 96%). Importantly, we show that this optimized N-alkylation procedure tolerates a wide structural variety of alkylating reagents, including primary alkyl halide and secondary alkyl tosylate electrophiles, while maintaining a high degree of N-1 regioselectivity.

Prospects for the use of the “model budget” in the distribution of equalization grants in Russia

2019 ◽  
pp. 21-38
Author(s):  
Alexander N. Deryugin ◽  
Ilya A. Sokolov
Keyword(s):  
Intergovernmental Relations ◽  
Unfunded Mandates ◽  
Interregional Inequality ◽  
Alternative Approach ◽  
The Russian Federation ◽  
Regional Authorities ◽  
High Degree ◽  
Equalization Grants ◽  
The Impact ◽  
Budget Expenditure

The paper analyzes the impact of the “model budget” on the problems of intergovernmental relations in the Russian Federation: a high proportion of expenditure obligations of regional and local budgets and a high degree of interregional inequality in fiscal capacity and socio-economic development. It was concluded that the planned broader use of the “model budget” will not solve the problem of unfunded mandates and will lead first to a significant reduction in incentives for regional authorities to develop the territorial revenue base, and then to economic slowdown in the country. As an alternative approach to improving intergovernmental relations, options are being considered for adjusting the parameters of the equalization transfers distribution formula, the procedure for determining their total volume and calculating the budget expenditure index. In solving the problem of unfunded mandates, an equally important role is given to the procedure for preparing a financial and economic rationale for draft laws.

Агрономическая эффективность промышленной (голландской) технологии возделывания картофеля

2018 ◽  
Author(s):  
C. Coy ◽  
A.V. Shuravilin ◽  
O.A. Zakharova
Keyword(s):  
Heavy Metals ◽  
Regression Analysis ◽  
Positive Response ◽  
Growth Yield ◽  
Correlation And Regression Analysis ◽  
Yield And Quality ◽  
Quality Of Products ◽  
High Degree ◽  
The Impact

Приведены результаты исследований по изучению влияния промышленной технологии возделывания картофеля на развитие, урожайность и качество продукции. Выявлена положительная реакция растений на подкормку K2SO4 в период посадки. Корреляционно-регрессионный анализ урожайности и качества клубней выявил высокую степень достоверности результатов опыта. Содержание нитратов и тяжелых металлов в клубнях было ниже допустимых величин.The results of studies on the impact of industrial technology of potato cultivation on growth, yield and quality of products. There was a positive response of plants to fertilizer K2SO4 in the period of planting. Correlation and regression analysis of yield and quality of tubers revealed a high degree of reliability of the results of experience. The contents of nitrates and heavy metals in tubers was below the permissible values.

Te inf uence of ergonomic factors on the formation of occupational risk of health disorders of agricultural machine operators

2019 ◽  
Vol 1 (7) ◽  
pp. 400-405
Author(s):  
Tamara A. Novikova ◽  
Aleksey N. Danilov ◽  
Vladimir F. Spirin
Keyword(s):  
Physical Activity ◽  
Functional Condition ◽  
Anthropometric Data ◽  
Agricultural Machine ◽  
Machine Operators ◽  
Health Disorders ◽  
Space Layout ◽  
Combine Harvesters ◽  
High Degree ◽  
The Impact

Introduction. T e leading place in the structure of occupational morbidity of agricultural machine operators is occupied by vertebroneurological diseases, the development of which can be associated with the impact of ergonomic factors of labor activity. T e aim of the study is to assess the ergonomic factors of working conditions on mobile agricultural machinery and to identify their impact on the formation of health disorders of agricultural machine operators. Materials and methods. Complex physiological and ergonomic researches at operation of tractors and combine harvesters of old samples of domestic production including an assessment of the organization of workplaces on compliance to requirements of ergonomics and anthropometric data of workers, temporary, statodynamic, biomechanical characteristics of working poses and movements, a functional condition of machine operators (130 people aged 20–45 years with professional experience of work not less than three years) in dynamics of a work shift are carried out. Anthropometric studies were conducted among male machine operators (663 people) aged 18–59 years and with experience in the profession for more than three years. Results. The discrepancy between the size and space-layout parameters of workplaces ergonomic requirements and anthropometric data of machine operators, causing the formation of uncomfortable working positions, increasing physical activity and the severity of the labor process. A high degree of correlation between changes in the parameters of the neuromuscular system and the severity of the discrepancy between the ergonomic parameters of anthropometric characteristics of machine operators (r=0,7). T e results of the research allowed to determine the priority measures for the prevention of vertebroneurological diseases in agricultural machine operators. Conclusions. T e organization of workplaces on domestic tractors and combine harvesters of old samples does not meet the ergonomic requirements and anthropometric data of machine operators, which is the reason for the formation of an uncomfortable working posture, increased statodynamic physical activity, early development of fatigue and fatigue in the process, which can cause the development of pathological conditions of the spine and ligamentous apparatus. Ergonomic improvement of workplaces is one of the priority measures to preserve the health of agricultural machine operators.

scholarly journals Advertising Media Impact in Consumer Buying Behavior

2019 ◽  
Vol 8 ◽  
pp. 54-56
Author(s):  
Ashmita Dahal Chhetri
Keyword(s):  
Consumer Behavior ◽  
Young Male ◽  
Electronic Media ◽  
Buying Behavior ◽  
Media Impact ◽  
High Degree ◽  
The Impact ◽  
Buying Behaviors ◽  
The Relationship ◽  
Better Than

Advertisements have been used for many years to influence the buying behaviors of the consumers. Advertisements are helpful in creating the awareness and perception among the customers of a product. This particular research was conducted on the 100 young male and female who use different brands of product to check the influence of advertisement on their buying behavior while creating the awareness and building the perceptions. Correlation, regression and other statistical tools were used to identify the relationship between these variables. The results revealed that the relationship between media and consumer behavior is positive. The adve1tising impact on sales and there is positive and high degree relationship between advertising and consumer behavior. The impact on advertising of a product of electronic media is better than non-electronic media.

scholarly journals Measuring spatial price differentials at the basic heading level: a comparison of stochastic index number methods

2021 ◽  
Author(s):  
Sebastian Weinand
Keyword(s):  
Price Level ◽  
Consumer Price Index ◽  
Index Number ◽  
Price Data ◽  
Estimation Efficiency ◽  
Spatial Price ◽  
Price Comparisons ◽  
High Degree ◽  
The Impact

AbstractSpatial price comparisons rely to a high degree on the quality of the underlying price data that are collected within or across countries. Below the basic heading level, these price data often exhibit large gaps. Therefore, stochastic index number methods like the Country–Product–Dummy (CPD) method and the Gini–Eltetö–Köves–Szulc (GEKS) method are utilised for the aggregation of the price data into higher-level indices. Although the two index number methods produce differing price level estimates when prices are missing, the present paper demonstrates that both can be derived from exactly the same stochastic model. For a specific case of missing prices, it is shown that the formula underlying these price level estimates differs between the two methods only in weighting. The impact of missing prices on the efficiency of the price level estimates is analysed in two simulation studies. It can be shown that the CPD method slightly outperforms the GEKS method. Using micro data of Germany’s Consumer Price Index, it can be observed that more narrowly defined products improve estimation efficiency.

scholarly journals Rural Financial Development Impacts on Agricultural Technology Innovation: Evidence from China

2021 ◽  
Vol 18 (3) ◽  
pp. 1110
Author(s):  
Yuyu Liu ◽  
Duan Ji ◽  
Lin Zhang ◽  
Jingjing An ◽  
Wenyan Sun
Keyword(s):  
Economic Development ◽  
Financial Development ◽  
Agricultural Development ◽  
Technology Innovation ◽  
Agricultural Technology ◽  
Rural Finance ◽  
Rural Economic Development ◽  
High Degree ◽  
The Impact ◽  
Positive Effect

Agricultural technology innovation is key for improving productivity, sustainability, and resilience in food production and agriculture to contribute to public health. Using panel data of 31 provinces in China from 2003 to 2015, this study examines the impact of rural financial development on agricultural technology innovation from the perspective of rural financial scale and rural finance efficiency. Furthermore, it examines how the effects of rural financial development vary in regions with different levels of marketization and economic development. The empirical results show that the development of rural finance has a significant and positive effect on the level of agricultural technology innovation. Rural finance efficiency has a significantly positive effect on innovation in regions with a low degree of marketization, while the rural financial scale has a significantly positive effect on technological innovation in regions with a high degree of marketization. Further analysis showed that improving the level of agricultural technology innovation is conducive to rural economic development. This study provides new insights into the effects of rural financial development on sustainable agricultural development from the perspective of agricultural technology innovation.

scholarly journals Greater fit and a greater gap

2019 ◽  
Vol 26 (4) ◽  
pp. 561-594
Author(s):  
Steven A. Brieger ◽  
Dirk De Clercq ◽  
Jolanda Hessels ◽  
Christian Pfeifer
Keyword(s):  
Life Satisfaction ◽  
Institutional Environment ◽  
Entrepreneurial Activity ◽  
Worker Rights ◽  
Content Type ◽  
Person Environment Fit ◽  
High Power Distance ◽  
High Degree ◽  
The Impact ◽  
Low Uncertainty

Purpose The purpose of this paper is to understand how national institutional environments contribute to differences in life satisfaction between entrepreneurs and employees. Design/methodology/approach Leveraging person–environment fit and institutional theories and using a sample of more than 70,000 entrepreneurs and employees from 43 countries, the study investigates how the impact of entrepreneurial activity on life satisfaction differs in various environmental contexts. An entrepreneur’s life satisfaction arguably should increase when a high degree of compatibility or fit exists between his or her choice to be an entrepreneur and the informal and formal institutional environment. Findings The study finds that differences in life satisfaction between entrepreneurs and employees are larger in countries with high power distance, low uncertainty avoidance, extant entrepreneurship policies, low commercial profit taxes and low worker rights. Originality/value This study sheds new light on how entrepreneurial activity affects life satisfaction, contingent on the informal and formal institutions in a country that support entrepreneurship by its residents.

The academic profession in Russia’s two capitals: The impact of 20 years of transition

2017 ◽  
Vol 16 (5) ◽  
pp. 626-644 ◽  
Author(s):  
Elizaveta Sivak ◽  
Maria Yudkevich
Keyword(s):  
Large Scale ◽  
Academic Career ◽  
Academic Profession ◽  
University Faculty ◽  
Key Characteristics ◽  
Personal Strain ◽  
High Degree ◽  
The Impact ◽  
Russian Universities

This paper studies the dynamics of key characteristics of the academic profession in Russia based on the analysis of university faculty in the two largest cities in Russia – Moscow and St Petersburg. We use data on Russian university faculty from two large-scale comparative studies of the academic profession (‘The Carnegie Study’ carried out in 1992 in 14 countries, including Russia, and ‘The Changing Academic Profession Study’, 2007–2012, with 19 participating countries and which Russia joined in 2012) to look at how faculty’s characteristics and attitudes toward different aspects of their academic life changed over 20 years (1992–2011) such as faculty’s views on reasons to leave or to stay at a university, on university’s management and the role of faculty in decision making. Using the example of universities in the two largest Russian cities, we demonstrate that the high degree of overall centralization of governance in Russian universities barely changed in 20 years. Our paper provides comparisons of teaching/research preferences and views on statements concerning personal strain associated with work, academic career perspectives, etc., not only in Russian universities between the years 1992 and 2012, but also in Russia and other ‘Changing Academic Profession’ countries.

scholarly journals Identification of the degree of impact of dams on the hydrologic regime of semi-arid rivers: an evaluation of the DHRAM method

RBRH ◽  
2017 ◽  
Vol 22 (0) ◽  
Author(s):  
Naiah Caroline Rodrigues de Souza ◽  
◽  
Andrea Sousa Fontes ◽  
Lafayette Dantas da Luz ◽  
Sandra Maria Conceição Pinheiro ◽  
...  
Keyword(s):  
Hydrological Regime ◽  
Flow Regulation ◽  
Hydrologic Regime ◽  
Local Conditions ◽  
Operating Rules ◽  
Hydrologic Variability ◽  
High Degree ◽  
The Impact ◽  
Semi Arid

ABSTRACT The flow regulation that results from the implantation of dams causes consequences to the river ecosystems due to the modification on the characteristics of the hydrologic regime. The investigation of these changes become relevant, mainly in semi-arid regions where there is a great amount of these hydraulic structures and lack of such analyzes. Considering the above, this paper aims to evaluate the Dundee Hydrological Regime Alteration Method (DHRAM) through the classification of the degree of impact of dams located on rivers Itapicuru, Paraguaçu and their tributaries, verifying the adequacy of its use to represent the semi-arid hydrologic regime. Thereby, the DHRAM was applied in three versions: considering the thresholds that define the scores to classify the degree of impact in its original set (accordingly to Black et al. (2005)); with the adjustment of those thresholds to local conditions; and, with the regrouping of variables and adjustment of thresholds. The results showed that the method in its original set is applicable to semi-arid rivers, however it tends to be very restrictive against the high natural hydrologic variability characteristic of these rivers, and it ends up pointing to a high degree of alteration for dams that are known for not causing a very siginifcant flow regulation. The DHRAM with the regrouping of variables and the adjustment of thresholds presented the classification that approached the most to the known characteristics of the studied dams, being useful for the evaluation of the impact of dams still in project, and also to guide the adoption of operating rules that minimize the most significant hydrologic alterations that are identified.

scholarly journals Back to the Future? Immunoglobulin Therapy for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Healthcare ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1546
Author(s):  
Helen Brownlie ◽  
Nigel Speight
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Subcutaneous Administration ◽  
Immunoglobulin Therapy ◽  
Chronic Fatigue ◽  
Myalgic Encephalomyelitis ◽  
Placebo Control ◽  
Fatigue Syndrome ◽  
Symptom Exacerbation ◽  
High Degree ◽  
The Impact

The findings of controlled trials on use of intravenous immunoglobulin G (IV IgG) to treat myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are generally viewed as representing mixed results. On detailed review, a clearer picture emerges, which suggests that the potential therapeutic value of this intervention has been underestimated. Our analysis is consistent with the propositions that: (1) IgG is highly effective for a proportion of patients with severe and well-characterised ME/CFS; (2) responders can be predicted with a high degree of accuracy based on markers of immune dysfunction. Rigorous steps were taken in the research trials to record adverse events, with transient symptom exacerbation commonly experienced in both intervention and placebo control groups, suggesting that this reflected the impact of participation on people with an illness characterised by post-exertional symptom exacerbation. Worsening of certain specific symptoms, notably headache, did occur more commonly with IgG and may have been concomitant to effective treatment, being associated with clinical improvement. The findings emerging from this review are supported by clinical observations relating to treatment of patients with severe and very severe ME/CFS, for whom intramuscular and subcutaneous administration provide alternative options. We conclude that: (1) there is a strong case for this area of research to be revived; (2) pending further research, clinicians would be justified in offering a course of IgG to selected ME/CFS patients at the more severe end of the spectrum. As the majority of trial participants had experienced an acute viral or viral-like onset, we further suggest that IgG treatment may be pertinent to the care of some patients who remain ill following infection with SARS-CoV-2 virus.

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