Modelling India’s coal production with a negatively skewed curve-fitting model

India’s coal demand is forecast to increase at a rapid pace in the future due to the country’s economic and population growth. Analyzing the scope for future production of India’s domestic coal resources, therefore, plays a vital role in the country’s development of sound energy policies. This paper presents a quantitative scenario analysis of India’s potential future coal production by using a negatively skewed curve-fitting model and a range of estimates of the country’s ultimately recoverable resources (URR) of coal. The results show that the resource base is sufficient for India’s coal production to keep increasing over the next few decades, to reach between 2400 and 3200 Mt/y at 2050, depending on the assumed value of URR. A further analysis shows that the high end of this range, which corresponds to our ‘GSI’ scenario, can be considered as the probable upper-bound to India’s domestic coal production. Comparison of production based on the ‘GSI’ scenario with India’s predicted demand shows that the domestic production of coal will be insufficient to meet the country’s rising coal demand, with the gap between demand and production increasing from its current value of about 268 Mt/y to reach 300 Mt/y in 2035, and 700 Mt/y by 2050. This increasing gap will be challenging for the energy security of India

Phenotypic diversity, disease progression, and pathogenicity of MVK missense variants in mevalonic aciduria

Mevalonic aciduria (MVA) and hyperimmunoglobulinemia D syndrome (MKD/HIDS) are disorders of cholesterol biosynthesis caused by variants in the MVK gene and characterized by increased urinary excretion of mevalonic acid. So far, 30 MVA patients have been reported, suffering from recurrent febrile crises and neurologic impairment. Here, we present an in-depth analysis of the phenotypic spectrum of MVA and provide an in-silico pathogenicity model analysis of MVK missense variants. The phenotypic spectrum of 11 MVA patients (age range 0-51 years) registered in the Unified European Registry for Inherited Metabolic Disorders database was systematically analyzed using terms of the Human Phenotype Ontology. Biochemical, radiological as well as genetic characteristics were investigated. Six of eleven patients have reached adulthood and four have reached adolescence. One of the adolescent patients died at the age of 16 years and one patient died shortly after birth. Symptoms started within the first year of life, including episodic fever, developmental delay, ataxia, and ocular involvement. We also describe a case with absence of symptoms despite massive excretion of mevalonic acid. Pathogenic variants causing MVA cluster within highly conserved regions, which are involved in mevalonate and ATP binding. The phenotype of adult and adolescent MVA patients is more heterogeneous than previously assumed. Outcome varies from an asymptomatic course to early death. MVK variants cluster in functionally important and highly conserved protein domains and show high concordance regarding their expected pathogenicity

Phenotypic diversity, disease progression, and pathogenicity of MVK missense variants in mevalonic aciduria

none21siMevalonic aciduria (MVA) and hyperimmunoglobulinemia D syndrome (MKD/HIDS) are disorders of cholesterol biosynthesis caused by variants in the MVK gene and characterized by increased urinary excretion of mevalonic acid. So far, 30 MVA patients have been reported, suffering from recurrent febrile crises and neurologic impairment. Here, we present an in-depth analysis of the phenotypic spectrum of MVA and provide an in-silico pathogenicity model analysis of MVK missense variants. The phenotypic spectrum of 11 MVA patients (age range 0-51 years) registered in the Unified European Registry for Inherited Metabolic Disorders database was systematically analyzed using terms of the Human Phenotype Ontology. Biochemical, radiological as well as genetic characteristics were investigated. Six of eleven patients have reached adulthood and four have reached adolescence. One of the adolescent patients died at the age of 16 years and one patient died shortly after birth. Symptoms started within the first year of life, including episodic fever, developmental delay, ataxia, and ocular involvement. We also describe a case with absence of symptoms despite massive excretion of mevalonic acid. Pathogenic variants causing MVA cluster within highly conserved regions, which are involved in mevalonate and ATP binding. The phenotype of adult and adolescent MVA patients is more heterogeneous than previously assumed. Outcome varies from an asymptomatic course to early death. MVK variants cluster in functionally important and highly conserved protein domains and show high concordance regarding their expected pathogenicity.openBrennenstuhl H.; Nashawi M.; Schroter J.; Baronio F.; Beedgen L.; Gleich F.; Jeltsch K.; von Landenberg C.; Martini S.; Simon A.; Thiel C.; Tsiakas K.; Opladen T.; Kolker S.; Hoffmann G.F.; Haas D.; Garcia-Cazorla A.; Dionisi-Vici C.; Martinelli D.; Kozich V.; Scarpa M.Brennenstuhl H.; Nashawi M.; Schroter J.; Baronio F.; Beedgen L.; Gleich F.; Jeltsch K.; von Landenberg C.; Martini S.; Simon A.; Thiel C.; Tsiakas K.; Opladen T.; Kolker S.; Hoffmann G.F.; Haas D.; Garcia-Cazorla A.; Dionisi-Vici C.; Martinelli D.; Kozich V.; Scarpa M