2,575 research outputs found
Development of a chemical heater for a Mars rough-landing capsule
Chemical reaction heater for Mars rough-landing capsul
Dapagliflozin stimulates glucagon secretion at high glucose: experiments and mathematical simulations of human A-cells.
Glucagon is one of the main regulators of blood glucose levels and dysfunctional stimulus secretion coupling in pancreatic A-cells is believed to be an important factor during development of diabetes. However, regulation of glucagon secretion is poorly understood. Recently it has been shown that Na(+)/glucose co-transporter (SGLT) inhibitors used for the treatment of diabetes increase glucagon levels in man. Here, we show experimentally that the SGLT2 inhibitor dapagliflozin increases glucagon secretion at high glucose levels both in human and mouse islets, but has little effect at low glucose concentrations. Because glucagon secretion is regulated by electrical activity we developed a mathematical model of A-cell electrical activity based on published data from human A-cells. With operating SGLT2, simulated glucose application leads to cell depolarization and inactivation of the voltage-gated ion channels carrying the action potential, and hence to reduce action potential height. According to our model, inhibition of SGLT2 reduces glucose-induced depolarization via electrical mechanisms. We suggest that blocking SGLTs partly relieves glucose suppression of glucagon secretion by allowing full-scale action potentials to develop. Based on our simulations we propose that SGLT2 is a glucose sensor and actively contributes to regulation of glucagon levels in humans which has clinical implications
Persuasive Technology for Learning in Business Context
"Persuasive Design is a relatively new concept which employs general principles of persuasion that can be implemented in persuasive technology. This concept has been introduced by BJ Fogg in 1998, who since then has further extended it to use computers for changing attitudes and behaviour. Such principles can be applied very well in learning and teaching: in traditional human-led learning, teachers always have employed persuasion as one of the elements of teaching. Persuasive technology moves these principles into the digital domain, by focusing on technology that inherently stimulates learners to learn more quickly and effectively. This is very relevant for the area of Business Management in several aspects: Consumer Behavior, Communications, Human Resource, Marketing & Advertising, Organisational Behavior & Leadership. The persuasive principles identified by BJ Fogg are: reduction, tunnelling, tailoring, suggestion, self-monitoring, surveillance, conditioning, simulation, social signals. Also relevant is the concept of KAIROS, which means the just-in-time, at the right place provision of information/stimulus. In the EuroPLOT project (2010-2013) we have developed persuasive learning objects and tools (PLOTs) in which we have applied persuasive designs and principles. In this context, we have developed a pedagogical framework for active engagement, based on persuasive design in which the principles of persuasive learning have been formalised in a 6-step guide for persuasive learning. These principles have been embedded in two tools – PLOTmaker and PLOTLearner – which have been developed for creating persuasive learning objects. The tools provide specific capability for implementing persuasive principles at the very beginning of the design of learning objects. The feasibility of employing persuasive learning concepts with these tools has been investigated in four different case studies with groups of teachers and learners from realms with distinctly different teaching and learning practices: Business Computing, language learning, museum learning, and chemical substance handling. These case studies have involved the following learner target groups: school children, university students, tertiary students, vocational learners and adult learners. With regards to the learning context, they address archive-based learning, industrial training, and academic teaching. Alltogether, these case studies include participants from Sweden, Africa (Madagascar), Denmark, Czech Republic, and UK. One of the outcomes of this investigation was that one cannot apply a common set of persuasive designs that would be valid for general use in all situations: on the contrary, the persuasive principles are very specific to learning contexts and therefore must be specifically tailored for each situation. Two of these case studies have a direct relevance to education in the realm of Business Management: Business Computing and language learning (for International Business). In this paper we will present the first results from the evaluation of persuasive technology driven learning in these two relevant areas.
Differential cross section for neutron-proton bremsstrahlung
The neutron-proton bremsstrahlung process is known to be
sensitive to meson exchange currents in the nucleon-nucleon interaction. The
triply differential cross section for this reaction has been measured for the
first time at the Los Alamos Neutron Science Center, using an intense, pulsed
beam of up to 700 MeV neutrons to bombard a liquid hydrogen target. Scattered
neutrons were observed at six angles between 12 and 32, and the
recoil protons were observed in coincidence at 12, 20, and
28 on the opposite side of the beam. Measurement of the neutron and
proton energies at known angles allows full kinematic reconstruction of each
event. The data are compared with predictions of two theoretical calculations,
based on relativistic soft-photon and non-relativistic potential models.Comment: 5 pages, 3 figure
Persuasive Technology for Learning and Teaching – The EuroPLOT Project
The concept of persuasive design has demonstrated its benefits by changing human behavior in certain situations, but in the area of education and learning, this approach has rarely been used. To change this and to study the feasibility of persuasive technology in teaching and learning, the EuroPLOT project (PLOT = Persuasive Learning Objects and Technologies) has been funded 2010-2013 by the Education, Audiovisual and Culture Executive Agency (EACEA) in the Life-long Learning (LLL) programme. In this program two tools have been developed (PLOTMaker and PLOTLearner) which allow to create learning objects with inherently persuasive concepts embedded. These tools and the learning objects have been evaluated in four case studies: language learning (Ancient Hebrew), museum learning (Kaj Munk Museum, Denmark), chemical handling, and academic Business Computing. These case studies cover a wide range of different learning styles and learning groups, and the results obtained through the evaluation of these case studies show the wide range of success of persuasive learning. They also indicate the limitations and areas where improvements are required
Electroencephalogram variability in patients with cirrhosis associates with the presence and severity of hepatic encephalopathy
BACKGROUND & AIMS: The outputs of physiological systems fluctuate in a complex manner even under resting conditions. Decreased variability or increased regularity of these outputs is documented in several disease states. Changes are observed in the spatial and temporal configuration of the electroencephalogram (EEG) in patients with hepatic encephalopathy (HE), but there is no information on the variability of the EEG signal in this condition. The aim of this study was to measure and characterize EEG variability in patients with cirrhosis and to determine its relationship to neuropsychiatric status. METHODS: Eyes-closed, awake EEGs were obtained from 226 patients with cirrhosis, classified, using clinical and psychometric criteria, as neuropsychiatrically unimpaired (n=127) or as having minimal (n=21) or overt (n=78) HE, and from a reference population of 137 healthy controls. Analysis of EEG signal variability was undertaken using continuous wavelet transform and sample entropy. RESULTS: EEG variability was reduced in the patients with cirrhosis compared with the reference population (coefficient of variation: 21.2% [19.3-23.4] vs. 22.4% [20.8-24.5]; p<0.001). A significant association was observed between EEG variability and neuropsychiatric status; thus, variability was increased in the patients with minimal HE compared with their neuropsychiatrically unimpaired counterparts (sample entropy: 0.98 [0.87-1.14] vs. 0.83 [0.75-0.95]; p=0.02), and compared with the patients with overt HE (sample entropy: 0.98 [0.87-1.14] vs. 0.82 [0.71-1.01]; p=0.01). CONCLUSIONS: Variability of the EEG is associated with both the presence and severity of HE. This novel finding may provide new insights into the pathophysiology of HE and provide a means for monitoring patients over time. LAY SUMMARY: Decreased variability or increased regularity of physiological systems is documented in several disease states. Variability of the electroencephalogram was found to be associated with both the presence and severity of brain dysfunction in patients with chronic liver disease
A Hierarchical Approach to Protein Molecular Evolution
Biological diversity has evolved despite the essentially infinite complexity
of protein sequence space. We present a hierarchical approach to the efficient
searching of this space and quantify the evolutionary potential of our approach
with Monte Carlo simulations. These simulations demonstrate that non-homologous
juxtaposition of encoded structure is the rate-limiting step in the production
of new tertiary protein folds. Non-homologous ``swapping'' of low energy
secondary structures increased the binding constant of a simulated protein by
relative to base substitution alone. Applications of our approach
include the generation of new protein folds and modeling the molecular
evolution of disease.Comment: 15 pages. 2 figures. LaTeX styl
Metformin, but not rosiglitazone, attenuates the increasing plasma levels of a new cardiovascular marker, fibulin-1, in patients with type 2 diabetes
OBJECTIVE
The extracellular matrix protein fibulin-1 is upregulated in the arterial wall in type 2 diabetes (T2D) and circulates in increased concentrations in diabetes. Metformin is an antidiabetic drug with beneficial cardiovascular disease effects in diabetes. We hypothesized that metformin would influence the increased level of plasma fibulin-1 in diabetes.
RESEARCH DESIGN AND METHODS
After a 4-week run-in period, 371 eligible patients with T2D were randomized to treatment groups in a factorial design including insulin alone (control), +metformin, +rosiglitazone, or +both metformin and rosiglitazone. Plasma fibulin-1 was analyzed at the beginning of the study and after 18 and 24 months.
RESULTS
Plasma fibulin-1 increased in all groups throughout the 2-year period; however, the increase was strongly attenuated among patients treated with metformin. A highly significant difference was observed when the mean change in plasma fibulin-1 was compared between metformin- and non–metformin-treated individuals both at 18 and 24 months of treatment, but rosiglitazone had no effect. Metformin and rosiglitazone alone reduced the HbA1c levels to comparable levels and in combination even further.
CONCLUSIONS
Metformin attenuates the increase in plasma fibulin-1 concentrations in T2D, independently of glycemic effects. Changes in fibulin-1 may reflect an important element in diabetic arteriopathy that can be influenced by metformin.
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