A Mixed-Integer Programming Model for Optimal Allocation of COVID-19 Vaccines in Davao City

With the emergence of COVID-19 in Davao City, the need to acquire herd immunity through vaccination is paramount in averting the further spread of the disease in addition to complying with health and safety protocols. This study presents a reformulation of Smalley et al.’s (2015) oral cholera vaccine—mixed-integer programming model (OCV-MIP) to fit the context of the COVID-19 vaccination campaign in the city for 5 years, with consideration of the possible need for annual revaccination, given limited supply and budget resources, to minimize COVID-19 cases further. The population is divided into subgroups with associated incidence rates serving as the basis for the optimal allocation of vaccines. Different ways of population stratification by some combinations of risk areas and age group divisions were explored. The results revealed that it is optimal to prioritize the vaccination of subgroups with the highest incidence rates. Keywords: forecasting · COVID-19 · Davao City · LINGO · Mixed-Integer Programming · Optimization · Philippines · SARS-CoV-2 · Vaccine

Metabolic control of DNA methylation in naive pluripotent cells.

Naive epiblast and embryonic stem cells (ESCs) give rise to all cells of adults. Such developmental plasticity is associated with genome hypomethylation. Here, we show that LIF-Stat3 signaling induces genomic hypomethylation via metabolic reconfiguration. Stat3-/- ESCs show decreased α-ketoglutarate production from glutamine, leading to increased Dnmt3a and Dnmt3b expression and DNA methylation. Notably, genome methylation is dynamically controlled through modulation of α-ketoglutarate availability or Stat3 activation in mitochondria. Alpha-ketoglutarate links metabolism to the epigenome by reducing the expression of Otx2 and its targets Dnmt3a and Dnmt3b. Genetic inactivation of Otx2 or Dnmt3a and Dnmt3b results in genomic hypomethylation even in the absence of active LIF-Stat3. Stat3-/- ESCs show increased methylation at imprinting control regions and altered expression of cognate transcripts. Single-cell analyses of Stat3-/- embryos confirmed the dysregulated expression of Otx2, Dnmt3a and Dnmt3b as well as imprinted genes. Several cancers display Stat3 overactivation and abnormal DNA methylation; therefore, the molecular module that we describe might be exploited under pathological conditions

Metabolic control of DNA methylation in naive pluripotent cells.

Naive epiblast and embryonic stem cells (ESCs) give rise to all cells of adults. Such developmental plasticity is associated with genome hypomethylation. Here, we show that LIF-Stat3 signaling induces genomic hypomethylation via metabolic reconfiguration. Stat3-/- ESCs show decreased α-ketoglutarate production from glutamine, leading to increased Dnmt3a and Dnmt3b expression and DNA methylation. Notably, genome methylation is dynamically controlled through modulation of α-ketoglutarate availability or Stat3 activation in mitochondria. Alpha-ketoglutarate links metabolism to the epigenome by reducing the expression of Otx2 and its targets Dnmt3a and Dnmt3b. Genetic inactivation of Otx2 or Dnmt3a and Dnmt3b results in genomic hypomethylation even in the absence of active LIF-Stat3. Stat3-/- ESCs show increased methylation at imprinting control regions and altered expression of cognate transcripts. Single-cell analyses of Stat3-/- embryos confirmed the dysregulated expression of Otx2, Dnmt3a and Dnmt3b as well as imprinted genes. Several cancers display Stat3 overactivation and abnormal DNA methylation; therefore, the molecular module that we describe might be exploited under pathological conditions

Entrepreneurial growth and ownership under market socialism in China: a longitudinal case study of small business growth

How firms grow is still a mystery and a definitive explanation remains elusive. This is especially the case for emerging economies, where the development of research into business growth has been notably slow whilst emerging business ventures are developing at hyper speed. Since most empirical studies have focused on the quantitative differences in growth across firms, this paper adopts a longitudinal case study approach to explore the qualitative differences in terms of how various types of firm achieve their growth outcomes in the organisational development process over a prolonged period of time. Through a theoretical lens which focuses on growth process approaches, this study not only demonstrates that entrepreneurial processes take different forms and dimensions in different contexts, but it also provides insights into the interactions of various organisational factors underpinning the strategies and changes that lead to contrasting growth outcomes. Case study findings assert that the ownership factor is a key contingent factor that shapes management structure and resources which, in turn, affect particular entrepreneurial outcomes. Furthermore, a combination of leadership style and the approach to knowledge management also play critical roles in the learning process which, tends to determine the strategy choice of either high or low value added product strategy. The findings of this research are that small firms with a low value product strategy can improve their survival chances and growth through the vertical broadening of a product portfolio in synchrony with increasing production and technology advancement. The case study companies show a tendency to reinforce their industry position by adopting contrasting choices for growth. The paper addresses the challenges and managerial implications for Western company managers in different growth contexts