Pantothenate Kinase 1 Is Required to Support the Metabolic Transition from the Fed to the Fasted State

Coenzyme A (CoA) biosynthesis is regulated by the pantothenate kinases (PanK), of which there are four active isoforms. The PanK1 isoform is selectively expressed in liver and accounted for 40% of the total PanK activity in this organ. CoA synthesis was limited using a Pank1−/− knockout mouse model to determine whether the regulation of CoA levels was critical to liver function. The elimination of PanK1 reduced hepatic CoA levels, and fasting triggered a substantial increase in total hepatic CoA in both Pank1−/− and wild-type mice. The increase in hepatic CoA during fasting was blunted in the Pank1−/− mouse, and resulted in reduced fatty acid oxidation as evidenced by abnormally high accumulation of long-chain acyl-CoAs, acyl-carnitines, and triglycerides in the form of lipid droplets. The Pank1−/− mice became hypoglycemic during a fast due to impaired gluconeogenesis, although ketogenesis was normal. These data illustrate the importance of PanK1 and elevated liver CoA levels during fasting to support the metabolic transition from glucose utilization and fatty acid synthesis to gluconeogenesis and fatty acid oxidation. The findings also suggest that PanK1 may be a suitable target for therapeutic intervention in metabolic disorders that feature hyperglycemia and hypertriglyceridemia

Topology of Economic Systems

An economic topology can have many uses to the academician, student and practitioner. Refining a topology of economic systems helps bring together seemingly disparate characteristics and point out potential long run trends. The progression of economic systems over time and also brief explanations of each system are given. We argue that most modern economic systems have some remnants of earlier forms, that is, most economies today are some mixture of what might be considered pure systems. Measurable characteristics to identify a particular system are developed that allows progress to or from a particular classification to be charted for individual countries

Topology of Economic Systems

An economic topology can have many uses to the academician, student and practitioner. Refining a topology of economic systems helps bring together seemingly disparate characteristics and point out potential long run trends. The progression of economic systems over time and also brief explanations of each system are given. We argue that most modern economic systems have some remnants of earlier forms, that is, most economies today are some mixture of what might be considered pure systems. Measurable characteristics to identify a particular system are developed that allows progress to or from a particular classification to be charted for individual countries

Freeform Powder Molding for Rapid Tooling

Tooling development can be quite time consuming and costly. Several iterations may be required, and later product or process modifications may necessitate tooling redesign. Rapid prototyping techniques capable of meeting the structural requirements of short-run and end-use tooling will have a significant impact on the product development cycle. This paper presents a technique for producing tooling using the Freeform Powder Molding process. Resulting tooling can be made from a wide variety of readily available metal powders, and mechanical properties can be tailored for customized tool design and fabrication. The example presented in this paper focuses on the rapid production of tooling for sheet metal formingMechanical Engineerin

Comorbid Medical Conditions as Predictors of Overall Survival in Glioblastoma Patients

Glioblastoma (GBM) is an aggressive central nervous system tumor with a poor prognosis. This study was conducted to determine any comorbid medical conditions that are associated with survival in GBM. Data were collected from medical records of all patients who presented to VCU Medical Center with GBM between January 2005 and February 2015. Patients who underwent surgery/biopsy were considered for inclusion. Cox proportional hazards regression modeling was performed to assess the relationship between survival and sex, race, and comorbid medical conditions. 163 patients met inclusion criteria. Comorbidities associated with survival on individual-characteristic analysis included: history of asthma (Hazard Ratio [HR]: 2.63; 95% Confidence Interval [CI]: 1.24–5.58; p = 0.01), hypercholesterolemia (HR: 1.95; 95% CI: 1.09–3.50; p = 0.02), and incontinence (HR: 2.29; 95% CI: 0.95–5.57; p = 0.07). History of asthma (HR: 2.22; 95% CI: 1.02–4.83; p = 0.04) and hypercholesterolemia (HR: 1.99; 95% CI: 1.11–3.56; p = 0.02) were associated with shorter survival on multivariable analysis. Surgical patients with GBM who had a prior history of asthma or hypercholesterolemia had significantly higher relative risk for mortality on individual-characteristic and multivariable analyses