Effects of intraparticle heat and mass transfer during devolatilization of a single coal particle

The objective of the present work is to elucidate the influence of intraparticle mass and heat transfer phenomena on the overall rate and product yields during devolatilization of a single coal particle in an inert atmosphere. To this end a mathematical model has been formulated which covers transient devolatilization kinetics and intraparticle mass and heat transport. Secondary deposition reactions of tarry volatiles also are included. These specific features of the model allow a quantitative assessment to be made of the impact of major process conditions such as the coal particle size, the ambient pressure and the heating rate on the tar, gas and total volatile yield during devolatilization. Model predictions are compared to a limited number of experimental results, both from the present work and from various literature sources

Proeve van een nieuwe grondwet: hoofdstuk 7, openbare lichamen

Characteristic for the Concept as a whole is its — generally laudable — curtailment and simplification. In the field of ‘public bodies’ details as well as more important principles have become victims of this modernization. Undoubtedly this opens new and valuable possibilities for the legislator, especially in the field of municipal and provincial administration. An essential lack, however, is the omission of a clear statement of the principle and the main instruments of functional and territorial decentralization, a principle that is called a postulate’ in the explanatory statement of the Concept itself. The author deplores especially the proposed omission of the constitutional guarantee of a certain amount of autonomy of the townships and provinces, as is provided in the present constitution. He rejects the argument that no program issues, however important, should be included in the constitution. A principle such as that of decentralization, essential as it is for our legislation, deserves a place in our constitution. 'The author uses quotations from the constitutions of several European countries to demonstrate that the principle of decentralization is usually embedded in their constitutions. In a detailed, flexible constitution this principle would deserve extensive elaboration; in a constitution such as the authors of the Concept would like to see — i.e. a rigid, concise and formally juridical one —, it should at least be mentioned as a main principle

Excavation at Aguas Buenas, Robinson Crusoe Island, Chile, of a gunpowder magazine and the supposed campsite of Alexander Selkirk, together with an account of early navigational dividers

Excavations were undertaken of a ruined building at Aguas Buenas, identified as an 18th-century Spanish gunpowder magazine. Evidence was also found for the campsite of an early European occupant of the island. A case is made that this was Alexander Selkirk, a castaway here from 1704 to 1709. Selkirk was the model for Defoe’s Robinson Crusoe. A detailed discussion is given of a fragment of copper alloy identifi ed as being from a pair of navigational dividers

Fructose-1,6-Bisphosphatase Overexpression in Pancreatic β-Cells Results in Reduced Insulin Secretion : A New Mechanism for Fat-Induced Impairment of β-Cell Function

OBJECTIVE—Fructose-1,6-bisphosphatase (FBPase) is a gluconeogenic enzyme that is upregulated in islets or pancreatic β-cell lines exposed to high fat. However, whether specific β-cell upregulation of FBPase can impair insulin secretory function is not known. The objective of this study therefore is to determine whether a specific increase in islet β-cell FBPase can result in reduced glucose-mediated insulin secretion

Future glucose-lowering drugs for type 2 diabetes

The multivariable and progressive natural history of type 2 diabetes limits the effectiveness of available glucose-lowering drugs. Constraints imposed by comorbidities (notably cardiovascular disease and renal impairment) and the need to avoid hypoglycaemia, weight gain, and drug interactions further complicate the treatment process. These challenges have prompted the development of new formulations and delivery methods for existing drugs alongside research into novel pharmacological entities. Advances in incretin-based therapies include a miniature implantable osmotic pump to give continuous delivery of a glucagon-like peptide-1 receptor agonist for 6-12 months and once-weekly tablets of dipeptidyl peptidase-4 inhibitors. Hybrid molecules that combine the properties of selected incretins and other peptides are at early stages of development, and proof of concept has been shown for small non-peptide molecules to activate glucagon-like peptide-1 receptors. Additional sodium-glucose co-transporter inhibitors are progressing in development as well as possible new insulin-releasing biological agents and small-molecule inhibitors of glucagon action. Adiponectin receptor agonists, selective peroxisome proliferator-activated receptor modulators, cellular glucocorticoid inhibitors, and analogues of fibroblast growth factor 21 are being considered as potential new approaches to glucose lowering. Compounds that can enhance insulin receptor and post-receptor signalling cascades or directly promote selected pathways of glucose metabolism have suggested opportunities for future treatments. However, pharmacological interventions that are able to restore normal β-cell function and β-cell mass, normalise insulin action, and fully correct glucose homoeostasis are a distant vision

The structure of the PanD/PanZ protein complex reveals negative feedback regulation of pantothenate biosynthesis by coenzyme A.

Coenzyme A (CoA) is an ubiquitous and essential cofactor, synthesized from the precursor pantothenate. Vitamin biosynthetic pathways are normally tightly regulated, including the pathway from pantothenate to CoA. However, no regulation of pantothenate biosynthesis has been identified. We have recently described an additional component in the pantothenate biosynthetic pathway, PanZ, which promotes the activation of the zymogen, PanD, to form aspartate ?-decarboxylase (ADC) in a CoA-dependent manner. Here we report the structure of PanZ in complex with PanD, which reveals the structural basis for the CoA dependence of this interaction and activation. In addition, we show that PanZ acts as a CoA-dependent inhibitor of ADC catalysis. This inhibitory effect can effectively regulate the biosynthetic pathway to pantothenate, and thereby also regulate CoA biosynthesis. This represents a previously unobserved mode of metabolic regulation whereby a cofactor-utilizing protein negatively regulates the biosynthesis of the same cofactor

Metformin reduces liver glucose production by inhibition of fructose-1-6-bisphosphatase.

Metformin is a first-line drug for the treatment of individuals with type 2 diabetes, yet its precise mechanism of action remains unclear. Metformin exerts its antihyperglycemic action primarily through lowering hepatic glucose production (HGP). This suppression is thought to be mediated through inhibition of mitochondrial respiratory complex I, and thus elevation of 5'-adenosine monophosphate (AMP) levels and the activation of AMP-activated protein kinase (AMPK), though this proposition has been challenged given results in mice lacking hepatic AMPK. Here we report that the AMP-inhibited enzyme fructose-1,6-bisphosphatase-1 (FBP1), a rate-controlling enzyme in gluconeogenesis, functions as a major contributor to the therapeutic action of metformin. We identified a point mutation in FBP1 that renders it insensitive to AMP while sparing regulation by fructose-2,6-bisphosphate (F-2,6-P2), and knock-in (KI) of this mutant in mice significantly reduces their response to metformin treatment. We observe this during a metformin tolerance test and in a metformin-euglycemic clamp that we have developed. The antihyperglycemic effect of metformin in high-fat diet-fed diabetic FBP1-KI mice was also significantly blunted compared to wild-type controls. Collectively, we show a new mechanism of action for metformin and provide further evidence that molecular targeting of FBP1 can have antihyperglycemic effects