Friskrivningsklausuler från anställdas grova vårdslöshet och uppsåt - en studie och kritisk analys av gällande rätt

Syftet med uppsatsen är att utreda vilken möjlighet som finns i svensk rätt att i kommersiella avtal friskriva sig från principalansvaret. Som huvudregel gäller avtalsfrihet i kommersiella avtal, men vad gäller ansvarsfriskrivningar är friheten till viss del begränsad. De oskrivna principer som reglerar vilken omfattning en ansvarsfriskrivning får har till stor del utretts i både praxis och doktrin och blir alltmer framtolkade då det är fråga om eget vållande av skada. Den här uppsatsen ämnar istället utreda förhållandet då det är annan som vållat skadan, i det här fallet specifikt arbetstagare. Vad angår sådana ansvarsfriskrivningar är rättsläget fortfarande oklart vilket skapar en betydande risk för kontrahenter till kommersiella avtal vilka har anställda. Principalansvaret och dess räckvidd har varit föremål för diskussion under lång tid då ett alltför långtgående ansvar för arbetsgivaren medför risk för obilliga resultat. Ansvaret är främst utomobligatoriskt men till följd av rättstillämpningen ifråga om åsidosättandet av ansvarsbegränsningar har det fått betydelse även i kontraktuella förhållanden. Uppsatsen undersöker således sammanförandet av avtalsrätt och de syften som lagstiftaren haft i åtanke vid införandet av principalansvaret för att möjliggöra en diskussion kring huruvida rättstillämpningens angrepp på problemet är ändamålsenligt. Genomgående i uppsatsen följer ett kollisionsperspektiv. Centralt för utredningen är att det är fråga om två regleringar i motsatsförhållande som måste sammanföras vilket inte har gjorts på ett tillfredsställande sätt. Vikten av att domstolar följer syftet med en tillämpning av 36§ AvtL och att således en helhetsbedömning av avtalet ska ske lyfts fram som den viktigaste komponenten i frågan och den tidigare skapade gränsen beroende av grad av vållande ter sig ohållbar i de fall då fråga är om begränsning av principalansvaret vid grovt vållande eller uppsåt

The electrophysiology of the betacell based on single transmembrane protein characteristics

The electrophysiology of betacells is at the origin of insulin secretion. Betacells exhibit a complex behaviour upon stimulation with glucose including repeated and uninterrupted bursting. Mathematical modelling is most suitable to improve knowledge about the function of various transmembrane currents provided the model is based on reliable data. This is the first attempt to build a mathematical model for the betacell-electrophysiology in a bottom-up approach which relies on single protein conductivity data. The results of previous whole-cell-based models are reconsidered. The full simulation including all prominent transmembrane proteins in betacells is used to provide a functional interpretation of their role in betacell-bursting and an updated vantage point of betacell-electrophysiology. As a result of a number of in silico knock-out- and block-experiments the novel model makes some unexpected predictions: Single-channel conductivity data imply that calcium-gated potassium currents are rather small. Thus, their role in burst interruption has to be revisited. An alternative role in high calcium level oscillations is proposed and an alternative burst interruption model is presented. It also turns out that sodium currents are more relevant than expected so far. Experiments are proposed to verify these predictions.Comment: 28 pages, 5 figures, 54 references, 14 pages supplementary materia

Pulsatility of insulin release – a clinically important phenomenon

The mechanisms and clinical importance of pulsatile insulin release are presented against the background of more than half a century of companionship with the islets of Langerhans. The insulin-secreting β-cells are oscillators with intrinsic variations of cytoplasmic ATP and Ca2+. Within the islets the β-cells are mutually entrained into a common rhythm by gap junctions and diffusible factors (ATP). Synchronization of the different islets in the pancreas is supposed to be due to adjustment of the oscillations to the same phase by neural output of acetylcholine and ATP. Studies of hormone secretion from the perfused pancreas of rats and mice revealed that glucose induces pulses of glucagon anti-synchronous with pulses of insulin and somatostatin. The anti-synchrony may result from a paracrine action of somatostatin on the glucagon-producing α-cells. Purinoceptors have a key function for pulsatile release of islet hormones. It was possible to remove the glucagon and somatostatin pulses with maintenance of those of insulin with an inhibitor of the P2Y1 receptors. Knock-out of the adenosine A1 receptor prolonged the pulses of glucagon and somatostatin without affecting the duration of the insulin pulses. Studies of isolated human islets indicate similar relations between pulses of insulin, glucagon, and somatostatin as found during perfusion of the rodent pancreas. The observation of reversed cycles of insulin and glucagon adds to the understanding how the islets regulate hepatic glucose production. Current protocols for pulsatile intravenous infusion therapy (PIVIT) should be modified to mimic the anti-synchrony between insulin and glucagon normally seen in the portal blood

Discovery of the Barium Isotopes

Thirty-eight barium isotopes have so far been observed; the discovery of these isotopes is discussed. For each isotope a brief summary of the first refereed publication, including the production and identification method, is presented.Comment: to be published in At. Data Nucl. Data Table

Emergent global oscillations in heterogeneous excitable media: The example of pancreatic beta cells

Using the standard van der Pol-FitzHugh-Nagumo excitable medium model I demonstrate a novel generic mechanism, diversity, that provokes the emergence of global oscillations from individually quiescent elements in heterogeneous excitable media. This mechanism may be operating in the mammalian pancreas, where excitable beta cells, quiescent when isolated, are found to oscillate when coupled despite the absence of a pacemaker region.Comment: See home page http://lec.ugr.es/~julya

Discovery of Calcium, Indium, Tin, and Platinum Isotopes

Currently, twenty-four calcium, thirty-eight indium, thirty-eight tin and thirty-nine platinum isotopes have been observed and the discovery of these isotopes is discussed here. For each isotope a brief synopsis of the first refereed publication, including the production and identification method, is presented.Comment: to be published in At. Data Nuclear Data Tables, This updated paper combines manuscripts: 1004.4934 (Calcium), 1004.5266 (Indium), 1003.5127 (Tin), and 1006.4033 (Platinum

Discovery of palladium, antimony, tellurium, iodine, and xenon isotopes

Currently, thirty-eight palladium, thirty-eight antimony, thirty-nine tellurium, thirty-eight iodine, and forty xenon isotopes have been observed and the discovery of these isotopes is discussed here. For each isotope a brief synopsis of the first refereed publication, including the production and identification method, is presented.Comment: to be published in At. Data Nucl. Data Table

Oscillations, Intercellular Coupling, and Insulin Secretion in Pancreatic β Cells

Insulin is a potent metabolic regulator that is released by pancreatic beta-cells, which respond to body glucose concentrations. Here the authors explain the physiological basis of insulin release

Complex Patterns of Metabolic and Ca²⁺ Entrainment in Pancreatic Islets by Oscillatory Glucose

Glucose-stimulated insulin secretion is pulsatile and driven by intrinsic oscillations in metabolism, electrical activity, and Ca(2+) in pancreatic islets. Periodic variations in glucose can entrain islet Ca(2+) and insulin secretion, possibly promoting interislet synchronization. Here, we used fluorescence microscopy to demonstrate that glucose oscillations can induce distinct 1:1 and 1:2 entrainment of oscillations (one and two oscillations for each period of exogenous stimulus, respectively) in islet Ca(2+), NAD(P)H, and mitochondrial membrane potential. To our knowledge, this is the first demonstration of metabolic entrainment in islets, and we found that entrainment of metabolic oscillations requires voltage-gated Ca(2+) influx. We identified diverse patterns of 1:2 entrainment and showed that islet synchronization during entrainment involves adjustments of both oscillatory phase and period. All experimental findings could be recapitulated by our recently developed mathematical model, and simulations suggested that interislet variability in 1:2 entrainment patterns reflects differences in their glucose sensitivity. Finally, our simulations and recordings showed that a heterogeneous group of islets synchronized during 1:2 entrainment, resulting in a clear oscillatory response from the collective. In summary, we demonstrate that oscillatory glucose can induce complex modes of entrainment of metabolically driven oscillations in islets, and provide additional support for the notion that entrainment promotes interislet synchrony in the pancreas

Complex Patterns of Metabolic and Ca²⁺ Entrainment in Pancreatic Islets by Oscillatory Glucose

Glucose-stimulated insulin secretion is pulsatile and driven by intrinsic oscillations in metabolism, electrical activity, and Ca(2+) in pancreatic islets. Periodic variations in glucose can entrain islet Ca(2+) and insulin secretion, possibly promoting interislet synchronization. Here, we used fluorescence microscopy to demonstrate that glucose oscillations can induce distinct 1:1 and 1:2 entrainment of oscillations (one and two oscillations for each period of exogenous stimulus, respectively) in islet Ca(2+), NAD(P)H, and mitochondrial membrane potential. To our knowledge, this is the first demonstration of metabolic entrainment in islets, and we found that entrainment of metabolic oscillations requires voltage-gated Ca(2+) influx. We identified diverse patterns of 1:2 entrainment and showed that islet synchronization during entrainment involves adjustments of both oscillatory phase and period. All experimental findings could be recapitulated by our recently developed mathematical model, and simulations suggested that interislet variability in 1:2 entrainment patterns reflects differences in their glucose sensitivity. Finally, our simulations and recordings showed that a heterogeneous group of islets synchronized during 1:2 entrainment, resulting in a clear oscillatory response from the collective. In summary, we demonstrate that oscillatory glucose can induce complex modes of entrainment of metabolically driven oscillations in islets, and provide additional support for the notion that entrainment promotes interislet synchrony in the pancreas