EPR, ENDOR and DFT Studies on X-Irradiated Single Crystals of L-Lysine Monohydrochloride Monohydrate and L-Arginine Monohydrocloride Monohydrate

When proteins and DNA interact, arginine and lysine are the two amino acids most often in close contact with the DNA. In order to understand the radiation damage to DNA in vivo, which is always associated with protein, it is important to learn the radiation chemistry of arginine and lysine independently, and when complexed to DNA. This work studied X-irradiated single crystals of L-lysine monohydrochloride dihydrate (L-lysine·HCl·2H2O) and L-arginine monohydrochloride monohydrate (L-arginine·HCl·H2O) with EPR, ENDOR, EIE techniques and DFT calculations. In both crystal types irradiated at 66K, the carboxyl anion radical and the decarboxylation radical were detected. DFT calculations supported these assignments. Specifically, the calculations performed on the cluster models for the carboxyl anion radicals reproduced the proton transfers to the carboxyl group from the neighboring molecules through the hydrogen bonds. Moreover, computations supported the identification of one radical type as the guanidyl radical anion with an electron trapped by the guanidyl group. In addition, the radical formed by dehydrogenation of C5 was identified in the L-arginine·HCl·H2O crystals irradiated at 66K. For both crystal types, the deamination radicals and the dehydrogenation radicals were identified following irradiation at 298K. Different conformations of main-chain deamination radicals were detected at 66K and at 298K. In L-lysine·HCl·2H2O, these conformations are the result of the different rotation angles of the side chain. In L-arginine·HCl·H2O, one conformation at 66K has no O-H dipolar protons while the others have two O-H dipolar protons. In L-lysine·HCl·2H2O, two radicals with very similar sets of hyperfine couplings were identified as the result of dehydrogenation from C3 and C5. Two other radicals in low concentration detected only at 66K, were tentatively assigned as the radical dehydrogenated from C3 and the side-chain deamination radical. In L-argnine·HCl·H2O, the radicals from dehydrogenation at C5 and C2 also were identified. DFT calculations supported these assignments and reproduced conformations of these radicals.Finally, based on the radicals detected in the crystal irradated at 66K and at 298K, the annealing experiments from the irradiation at 66K, and the previous studies on the irradiated amino acids, the mechanisms of the irradiation damage on lysinie and arginine were proposed

Exploring the impact of South Africa's immigration policy (2000-to 2006) on the medical doctors' shortage—a critical realist perspective

South Africa is facing a severe shortage of medical doctors and has a government that is sceptical of reliance of foreign skills known as skilled immigration. The government and the national Department of Health (DoH) have implemented a variety of intervention measures in order to alleviate the negative impact of this shortage caused by medical skills shortage in the sector. However, the DoH's reluctance to recruit foreign medical doctors, and particularly its prohibition on the recruitment of doctors from South Africa's neighbouring countries, undermines the government's effort to increase the number of doctors in the health system. Skilled immigration, the importation of scarce skills from outside the country, made little progress with the enactment of the Immigration Act 13 of 2002. The priority of South Africa's immigration policy is still focused on controlling skilled immigration, as is underlined by its protectionism and restrictiveness. The Department of Home Affairs' (DHA) immigration policy and its counterproductive approach to attracting skilled foreign labour has drawn criticism from a wide range of people including academics, politicians and businesspeople. The DHA itself has in its white papers of 1999 and of 2017 admitted that its inflexible approach to immigration has resulted in the country's failure to attract skilled foreign workers. In this study, I use archived parliamentary meeting minutes and parliamentary documents as the primary data source to understand the deliberations of stakeholders on skilled immigration which resulted in the Immigration Act 13 of 2002. The Act had a direct effect on the DoH's approach to the recruitment of foreign medical doctors. More specifically, this dissertation aims to explore how stakeholders who were involved in the drafting process of the Immigration Act 13 of 2002 deliberated on the existing cultural and structural conditions that resulted in the Immigration Bill which preceded the Act. By exploring the changes in the immigration policy, the dissertation aims to understand the impact of the immigration policy and institutional xenophobia on the recruitment of foreign doctors. Margaret Archer's (1995) morphogenetic/morphostatic cycle is used to understand the development of South Africa's immigration policy from 2000 to 2006 as this was the period in which the discussion of the Immigration Bill started. I argue that institutional xenophobia which is manifested in South Africans' antagonism towards foreign nationals, the deeply-entrenched employment equity policy that promotes national workers, the weakened state of the civil society, and the consolidated power of the government in decision-making all contributed to the DoH's decision to restrict the recruitment of foreign medical doctors. In the absence of government's support, it is unlikely that there will be a conducive environment to put in place a skilled immigration policy that can harness skilled foreigners' skills and facilitate skilled foreigners' entry. This dissertation suggests that the government critically review its immigration policy which is deepening South Africa's skills gap in the medical field. This dissertation further recommends the government to consider the option of allowing foreign doctors to work in the private sector. This would not only increase the overall number of doctors in the health sector, it would also dispel the public's concern that the employment of foreign doctors would cost a hefty amount at the expense of the public

A stratification model of surface snow at Dome Fuji Station, Antarctica

A stratification model of surface snow on the ice sheet, which includes snow density evolution, is proposed. Using the temperature profile in the surface snow layer obtained at Dome Fuji Station, Antarctica, snow density evolution under various accumulation conditions was simulated. It is demonstrated that water vapor diffusion is very important for the snow density evolution, and temperature and accumulation at the snow surface are the most important factors that determine the future snow density profile below the surface

Competitive Strategy Suggestions for Electric Vehicle Companies -- Based on Consumer Purchasing Driving Factors

Promoting the use of electric vehicles can better contribute to environmental protection. Over the past decade, governments have provided a lot of support to the electric vehicle industry, attracting many companies enter into the industry. The sharp increase in sales and the market’s optimistic attitude towards the electric vehicle industry has prompted fierce competition in the industry. Previous studies on the strategies of electric vehicle companies focused on the analysis of corporate value chain and external environment, and paid little attention to the needs of consumers. This paper combines the consumer purchase theory with the corporate competitive strategy and helps the electric vehicle company to develop competitive strategy by determining the driving factors that affect consumers’ purchase of electric vehicles. To get a more complete understanding of consumer buying factors, this paper adopts mixed methods approach including semi-structured interview and survey. The research finds that consumers still believe that government policies have a significant impact on the development of the electric vehicle industry, mainly because of the attractiveness of environmentally friendly initiatives and car purchase subsidies to consumers. Through the investigation, this paper suggests that electric vehicle companies obtain major competitive advantages mainly by means of image differentiation, service differentiation and cost reduction. If the enterprise is rich in resources, it can adopt a focus strategy to focus on the battery technology of electric vehicles or to meet a specific market segment, otherwise the focus strategy will be risky

Online Meta-Critic Learning for Off-Policy Actor-Critic Methods

Off-Policy Actor-Critic (Off-PAC) methods have proven successful in a variety of continuous control tasks. Normally, the critic's action-value function is updated using temporal-difference, and the critic in turn provides a loss for the actor that trains it to take actions with higher expected return. In this paper, we introduce a novel and flexible meta-critic that observes the learning process and meta-learns an additional loss for the actor that accelerates and improves actor-critic learning. Compared to the vanilla critic, the meta-critic network is explicitly trained to accelerate the learning process; and compared to existing meta-learning algorithms, meta-critic is rapidly learned online for a single task, rather than slowly over a family of tasks. Crucially, our meta-critic framework is designed for off-policy based learners, which currently provide state-of-the-art reinforcement learning sample efficiency. We demonstrate that online meta-critic learning leads to improvements in avariety of continuous control environments when combined with contemporary Off-PAC methods DDPG, TD3 and the state-of-the-art SAC.Comment: NeurIPS 202

Metformin and Lactic Acidosis in Diabetic Patients

Metformin is the basic drug in the clinical treatment of Diabetes, often used in the treatment of Type 2 Diabetes Mellitus (T2DM).Its effect has been fully verified in the clinical treatment of T2DM. However, in the treatment of T2DM with metformin, there is still a certain probability of related lactic acidosis, and the fatality rate is high. Therefore, is the use of metformin drug treatment a direct risk factor for lactic acidosis in diabetic patients? This paper will review the hypoglycemic mechanism of metformin and related studies on lactic acidosis, so as to further explore the relationship between metformin and lactic acidosis in diabetic patients, and provide help and reference for metformin drugs in the clinical treatment of T2DM