Biological Roles and Therapeutic Potential of Hydroxy-Carboxylic Acid Receptors

In the recent past, deorphanization studies have described intermediates of energy metabolism to activate G protein-coupled receptors and to thereby regulate metabolic functions. GPR81, GPR109A, and GPR109B, formerly known as the nicotinic acid receptor family, are encoded by clustered genes and share a high degree of sequence homology. Recently, hydroxy-carboxylic acids were identified as endogenous ligands of GPR81, GPR109A, and GPR109B, and therefore these receptors have been placed into a novel receptor family of hydroxy-carboxylic acid (HCA) receptors. The HCA1 receptor (GPR81) is activated by the glycolytic metabolite 2-hydroxy-propionic acid (lactate), the HCA2 receptor is activated by the ketone body 3-hydroxy-butyric acid, and the HCA3 receptor (GPR109B) is a receptor for the β-oxidation intermediate 3-hydroxy-octanoic acid. While HCA1 and HCA2 receptors are present in most mammalian species, the HCA3 receptor is exclusively found in humans and higher primates. HCA receptors are expressed in adipose tissue and mediate anti-lipolytic effects in adipocytes through Gi-type G protein-dependent inhibition of adenylyl cyclase. HCA2 and HCA3 inhibit lipolysis during conditions of increased β-oxidation such as prolonged fasting, whereas HCA1 mediates the anti-lipolytic effects of insulin in the fed state. As HCA2 is a receptor for the established anti-dyslipidemic drug nicotinic acid, HCA1 and HCA3 also represent promising drug targets and several synthetic ligands for HCA receptors have been developed. In this article, we will summarize the deorphanization and pharmacological characterization of HCA receptors. Moreover, we will discuss recent progress in elucidating the physiological and pathophysiological role to further evaluate the therapeutic potential of the HCA receptor family for the treatment of metabolic disease

Measuring Relationship between Digital Skills and Employability

In the growing economies like Pakistan and other countries, digital skils such as computer, communication, internet and advance digital skills are predictable to offer possible employees a major rim in securing their jobs and also protecting relatively high-paying jobs. Digital skills are not dual it has ranges and stages. There are number of International organizations that are making efforts on improving the people’s employability. I need more data in order to know the relationship between digital skills and employability in terms of which level of digital skills are enough for civilizing emplyability.  In this study I observe the digital skills assosiation with the employabilty using the Paf-Kiet University and National Foods Limited as a comparative study. Findings highlighted that digital skills can be a interpreter of employnment, the level of digital skills necessary to achieve these jobs is very high as one might imagine. In the rising economies perspective, digital skills are linked with high status jobs mainly combine with other reasons such as higher education. Implementation strategy  on the basis of the finiding of this study in order to improve employabilty, advising that revise the education policy and training efforts should focus on digital skills. Key words: Digital Skills, employabilty, Students’s, Employers, Relationship

Evaluating The Factor Of Cost And Benefit Of Internal Audit

The financial and operational cost and benefits of internal auditing plays very vital role in the organizations. The main aim of this study is determine the importance and impact of both internal audit and internal audit outsourcing with in organizations. A 15 items perception of a financial and operational cost and benefit of internal audit usage survey was conduct to one organization of Oil and Gas Development Company Limited. The finding of the study shows that three variables were significant in the selection of internal audit but the two variables shows the negative results which indicate outsourcing is cheaper than in sourcing. A very common conclusion is that the internal facilities is more costly another choice to be used in outsourcing so that internal provider is less efficient than external providers as they developed the technological efficiencies, a study of this type would explain the factors dependable for the significance of in sourcing compare to outsourcing and to compare the cost and benefit of internal audit. Key Words: Cost, Benefit, Internal Audit, OGDCL, Pakista

Numerical Investigation of Double Corrugated Steel Plate Shear Walls

Recently, corrugated steel plate shear walls have been shown to be an efficient lateral force resisting system for building structures. Corrugated plates have higher out-of-plane stiffness and improved buckling stability in comparison with flat plates which result in improved hysteretic behavior. However, the thickness of the corrugated plates may be limited due to the cold-form process restrictions. This paper investigates the cyclic performance of double corrugated steel plate shear walls. One-story single-bay specimen was designed and modelled and parametric studies were performed. The parametric study considered the orientation of corrugated plates (horizontal or vertical), disconnection of infill plates from columns, disconnection of infill plates from each other, infill plate thickness and infill plate aspect ratio on cyclic performance of double corrugated steel plate shear walls. The present study results show that proper selection of the aforementioned parameters can lead to a desirable cyclic performance. In the end, a recommendation for calculating initial stiffness and ultimate strength of double corrugated steel plate shear walls is given

Micro foundations of strategic capability development: A case study within auto industry

The importance of firms’ adaptation processes is prominent in today’s business environment which is characterised by ever changing customers, technologies, and competition. Ever since Schumpeter’s (1942) classic work strategic renewal has been found crucial for firms’ adaptation to environmental change. The role of strategic renewal in firms’ adaptation processes includes development of capabilities for the purpose of sustainability of competitive advantage against environmental changes

Unpacking organisational culture for innovation in Australian mining industry

Innovation has become the backbone of organisations in today's increasingly changing environment. Research shows that many organisations fail to innovate due to a lack of a supportive culture. Particularly in the mining industry, with a dominant risk-averse mindset along with other barriers, such as capital intensiveness, frequent market fluctuations, and siloed and bureaucratic structures, developing an innovation culture is necessary for the future survival of the industry. However, the existing literature is still inconclusive regarding which cultural values promote innovation and is especially lacking in context-specific studies. Understanding of behaviours that should be promoted to support an innovation culture is still limited. Using a systematic literature review and 18 interviews with experts in the mining industry, this study unpacks the dimensions and behaviours that support innovation values in the context of the Australian mining industry. Findings from this study reveal 33 underlying cultural dimensions and specific organisational behaviours promoting an innovation culture. This study shed further light on how mining companies can support and promote an innovation culture

The Role Of Auditor Characteristics: Earnings Management and Audit Committee Effectiveness

This study aims to analyze the moderating effect of auditor characteristics on the relationship between audit committee effectiveness and earnings management. Mechanisms of good corporate governance can limit and control the opportunistic actions of management. A highly effective audit committee will reduce the prevalence of earnings management. In addition to the audit committee as an internal party that oversees the credibility of financial statements, it is also necessary to supervise external parties, through the use of external auditors. With expectations of reducing earnings manipulation, this study examines the effects of the combination of an effective audit committee and an independent auditor. The research sample selection uses a purposive judgmental non-probability sampling technique. The sample obtained is 754 firm years, consisting of three years of company observations in the Indonesian capital market between 2016 and 2018, except those in the financial sector. Earnings management is measured by accrual value using a modified Jones model. The independent variable of the study is the effectiveness of the audit committee (EFAC) which will be assessed using the DeZoort index. The results of the empirical testing support the research hypothesis; the more effective the audit committee is and the longer the external audit period is, the more prevalent earnings management will be. In addition, the more effective the audit committee is, coupled with the use of one of the big four auditors, the less prevalent earnings management will be, which means the auditor's reputation also strengthens the relationship between the effectiveness of the audit committee and earnings management. Further, the moderating effect of auditor specialization on the influence of the audit committee on earnings manipulation did not provide significant results