Almost Sure Stabilization for Adaptive Controls of Regime-switching LQ Systems with A Hidden Markov Chain

This work is devoted to the almost sure stabilization of adaptive control systems that involve an unknown Markov chain. The control system displays continuous dynamics represented by differential equations and discrete events given by a hidden Markov chain. Different from previous work on stabilization of adaptive controlled systems with a hidden Markov chain, where average criteria were considered, this work focuses on the almost sure stabilization or sample path stabilization of the underlying processes. Under simple conditions, it is shown that as long as the feedback controls have linear growth in the continuous component, the resulting process is regular. Moreover, by appropriate choice of the Lyapunov functions, it is shown that the adaptive system is stabilizable almost surely. As a by-product, it is also established that the controlled process is positive recurrent

State observability and observers of linear-time-invariant systems under irregular sampling and sensor limittations

Abstract-State observability and observer designs are investigated for linear-time-invariant systems in continuous time when the outputs are measured only at a set of irregular sampling time sequences. The problem is primarily motivated by systems with limited sensor information in which sensor switching generates irregular sampling sequences. State observability may be lost and the traditional observers may fail in general, even if the system has a full-rank observability matrix. It demonstrates that if the original system is observable, the irregularly sampled system will be observable if the sampling density is higher than some critical frequency, independent of the actual time sequences. This result extends Shannon's sampling theorem for signal reconstruction under periodic sampling to system observability under arbitrary sampling sequences. State observers and recursive algorithms are developed whose convergence properties are derived under potentially dependent measurement noises. Persistent excitation conditions are validated by designing sampling time sequences. By generating suitable switching time sequences, the designed state observers are shown to be convergent in mean square, with probability one, and with exponential convergence rates. Schemes for generating desired sampling sequences are summarized

Redefining Case Study

Abstract: In this paper the authors propose a more precise and encompass-ing definition of case study than is usually found. They support their defini-tion by clarifying that case study is neither a method nor a methodology nor a research design as suggested by others. They use a case study prototype of their own design to propose common properties of case study and demon-strate how these properties support their definition. Next, they present sev-eral living myths about case study and refute them in relation to their definition. Finally, they discuss the interplay between the terms case study and unit of analysis to further delineate their definition of case study. The target audiences for this paper include case study researchers, research de-sign and methods instructors, and graduate students interested in case study research

Entrepreneurial Value Creation in the Cloud: Exploring the Value Dimensions of the Business Model

Part 5: Research in ProgressInternational audienceCloud computing’s potential in creating and capturing business value is being increasingly acknowledged. Existing empirical studies of business value in cloud computing have focused on user organizations and large enterprises with legacy systems. Acknowledging the innovation opportunities created by cloud, we study entrepreneurial cloud service providers. In this paper we conduct an exploratory study of six cloud-based start-up firms in India. We examine the value dimensions of the business model concept to study entrepreneurial value creation in the cloud. We find that cloud is a key resource in the structural configuration of their business model and enables the value proposition

Preparation of biogenic gas vesicle nanostructures for use as contrast agents for ultrasound and MRI

Gas vesicles (GVs) are a unique class of gas-filled protein nanostructures that are detectable at subnanomolar concentrations and whose physical properties allow them to serve as highly sensitive imaging agents for ultrasound and MRI. Here we provide a protocol for isolating GVs from native and heterologous host organisms, functionalizing these nanostructures with moieties for targeting and fluorescence, characterizing their biophysical properties and imaging them using ultrasound and MRI. GVs can be isolated from natural cyanobacterial and haloarchaeal host organisms or from Escherichia coli expressing a heterologous GV gene cluster and purified using buoyancy-assisted techniques. They can then be modified by replacing surface-bound proteins with engineered, heterologously expressed variants or through chemical conjugation, resulting in altered mechanical, surface and targeting properties. Pressurized absorbance spectroscopy is used to characterize their mechanical properties, whereas dynamic light scattering (DLS)and transmission electron microscopy (TEM) are used to determine nanoparticle size and morphology, respectively. GVs can then be imaged with ultrasound in vitro and in vivo using pulse sequences optimized for their detection versus background. They can also be imaged with hyperpolarized xenon MRI using chemical exchange saturation transfer between GV-bound and dissolved xenon—a technique currently implemented in vitro. Taking 3–8 d to prepare, these genetically encodable nanostructures enable multimodal, noninvasive biological imaging with high sensitivity and potential for molecular targeting

SEIPIN Regulates Lipid Droplet Expansion and Adipocyte Development by Modulating the Activity of Glycerol-3-phosphate Acyltransferase

Berardinelli-Seip congenital lipodystrophy 2 (BSCL2) is caused by loss-of-function mutations in SEIPIN, a protein implicated in both adipogenesis and lipid droplet expansion but whose molecular function remains obscure. Here, we identify physical and functional interactions between SEIPIN and microsomal isoforms of glycerol-3-phosphate acyltransferase (GPAT) in multiple organisms. Compared to controls, GPAT activity was elevated in SEIPIN-deficient cells and tissues and GPAT kinetic values were altered. Increased GPAT activity appears to underpin the block in adipogenesis and abnormal lipid droplet morphology associated with SEIPIN loss. Overexpression of Gpat3 blocked adipogenesis, and Gpat3 knockdown in SEIPIN-deficient preadipocytes partially restored differentiation. GPAT overexpression in yeast, preadipocytes, and fly salivary glands also formed supersized lipid droplets. Finally, pharmacological inhibition of GPAT in Seipin-/- mouse preadipocytes partially restored adipogenesis. These data identify SEIPIN as an evolutionarily conserved regulator of microsomal GPAT and suggest that GPAT inhibitors might be useful for the treatment of human BSCL2 patients

Lipidomic profiling identifies signatures of metabolic risk

BACKGROUND: Metabolic syndrome (MetS), the clustering of metabolic risk factors, is associated with cardiovascular disease risk. We sought to determine if dysregulation of the lipidome may contribute to metabolic risk factors. METHODS: We measured 154 circulating lipid species in 658 participants from the Framingham Heart Study (FHS) using liquid chromatography-tandem mass spectrometry and tested for associations with obesity, dysglycemia, and dyslipidemia. Independent external validation was sought in three independent cohorts. Follow-up data from the FHS were used to test for lipid metabolites associated with longitudinal changes in metabolic risk factors. RESULTS: Thirty-nine lipids were associated with obesity and eight with dysglycemia in the FHS. Of 32 lipids that were available for replication for obesity and six for dyslipidemia, 28 (88%) replicated for obesity and five (83%) for dysglycemia. Four lipids were associated with longitudinal changes in body mass index and four were associated with changes in fasting blood glucose in the FHS. CONCLUSIONS: We identified and replicated several novel lipid biomarkers of key metabolic traits. The lipid moieties identified in this study are involved in biological pathways of metabolic risk and can be explored for prognostic and therapeutic utility.The Framingham Heart Study is funded by National Institutes of Health (NIH) contract N01-HC-25195. This study was made possible by a CRADA between BG Medicine, Inc., Boston University, and the NHLBI, and the laboratory work for this research was supported by the Division of Intramural Research of the National Heart, Lung, and Blood Institute (NHLBI). Analytical work was funded by the Division of Intramural Research of NHLBI as well as the Center for Information Technology, NIH, Bethesda, MD. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services. The PESA study is supported by a non-competitive unrestricted grant shared between the National Center for Cardiovascular Research Carlos III (CNIC) and the Bank of Santander. The PESA study is a noncommercial study independent of the health and pharmaceutical industry. The CNIC is supported by the Spanish Ministry of Science, Innovation and Universities, the Instituto de Salud Carlos III, and the proCNIC Foundation. The study was partially funded by a grant from AstraZeneca (TANSNIP project). JMO is supported by the US Department of Agriculture, under agreement no. 8050-51000-098-00D. MPO and MJ acknowledge an Institute of Health Carlos III grant (PI 17-00134). This research was in part funded by the Spanish Ministry of Economy and Competitiveness, Institute of Health Carlos III (PI14/00328), co-financed by FEDER funds from the European Union ('A way to built Europe'), and the Generalitat of Catalonia, Department of Health(SLT002/16/00250) and Department of Business and Knowledge(2017SGR696) to R.P. MJ is a Serra Hunter Fellow.S

Chronic elevation of pulmonary microvascular pressure in chronic heart failure reduces bi-directional pulmonary fluid flux

Aims. Chronic heart failure leads to pulmonary vascular remodelling and thickening of the alveolar–capillary barrier. We examined whether this protective effect may slow resolution of pulmonary oedema consistent with decreased bi-directional fluid flux. Methods and results. Seven weeks following left coronary artery ligation, we measured both fluid flux during an acute rise in left atrial pressure (n = 29) and intrinsic alveolar fluid clearance (n = 45) in the isolated rat lung. Chronic elevation of pulmonary microvascular pressure prevented pulmonary oedema and decreased lung compliance when left atrial pressure was raised to 20 cmH2O, and was associated with reduced expression of endothelial aquaporin 1 (P = 0.03). However, no other changes were found in mediators of fluid flux or cellular fluid channels. In isolated rat lungs, chronic LV dysfunction (LV end-diastolic pressure and infarct circumference) was also inversely related to alveolar fluid clearance (P ≤ 0.001). The rate of pulmonary oedema reabsorption was estimated by plasma volume expansion in eight patients with a previous clinical history of chronic heart failure and eight without, who presented with acute pulmonary oedema. Plasma volume expansion was reduced at 24 h in those with chronic heart failure (P = 0.03). Conclusions. Chronic elevation of pulmonary microvascular pressure in CHF leads to decreased intrinsic bi-directional fluid flux at the alveolar–capillary barrier. This adaptive response defends against alveolar flooding, but may delay resolution of alveolar oedema.A National Health and Medical Research Council (NHMRC) grant (#375129); Australian and New Zealand College of Anaesthetists (ANZCA) grant (#08/020); the Flinders Medical Centre Foundation