Miracle-dz/UniFAR-FTUs huggingface dataset:
Cardiac Ryanodine Receptor (Ryr2)-mediated Calcium Signals Specifically Promote Glucose Oxidation via Pyruvate Dehydrogenase*

Cardiac ryanodine receptor (Ryr2) Ca2+ release channels and cellular metabolism are both disrupted in heart disease. Recently, we demonstrated that total loss of Ryr2 leads to cardiomyocyte contractile dysfunction, arrhythmia, and reduced heart rate. Acute total Ryr2 ablation also impaired metabolism, but it was not clear whether this was a cause or consequence of heart failure. Previous in vitro studies revealed that Ca2+ flux into the mitochondria helps pace oxidative metabolism, but there is limited in vivo evidence supporting this concept. Here, we studied heart-specific, inducible Ryr2 haploinsufficient (cRyr2Δ50) mice with a stable 50% reduction in Ryr2 protein. This manipulation decreased the amplitude and frequency of cytosolic and mitochondrial Ca2+ signals in isolated cardiomyocytes, without changes in cardiomyocyte contraction. Remarkably, in the context of well preserved contractile function in perfused hearts, we observed decreased glucose oxidation, but not fat oxidation, with increased glycolysis. cRyr2Δ50 hearts exhibited hyperphosphorylation and inhibition of pyruvate dehydrogenase, the key Ca2+-sensitive gatekeeper to glucose oxidation. Metabolomic, proteomic, and transcriptomic analyses revealed additional functional networks associated with altered metabolism in this model. These results demonstrate that Ryr2 controls mitochondrial Ca2+ dynamics and plays a specific, critical role in promoting glucose oxidation in cardiomyocytes. Our findings indicate that partial RYR2 loss is sufficient to cause metabolic abnormalities seen in heart disease.
Flexibility of Syntrophic Enzyme Systems in Desulfovibrio Species Ensures Their Adaptation Capability to Environmental Changes

ABSTRACT The mineralization of organic matter in anoxic environments relies on the cooperative activities of hydrogen producers and consumers obligately linked by interspecies metabolite exchange in syntrophic consortia that may include sulfate reducing species such as Desulfovibrio. To evaluate the metabolic flexibility of syntrophic Desulfovibrio to adapt to naturally fluctuating methanogenic environments, we studied Desulfovibrio alaskensis strain G20 grown in chemostats under respiratory and syntrophic conditions with alternative methanogenic partners, Methanococcus maripaludis and Methanospirillum hungatei, at different growth rates. Comparative whole-genome transcriptional analyses, complemented by G20 mutant strain growth experiments and physiological data, revealed a significant influence of both energy source availability (as controlled by dilution rate) and methanogen on the electron transfer systems, ratios of interspecies electron carriers, energy generating systems, and interspecies physical associations. A total of 68 genes were commonly differentially expressed under syntrophic versus respiratory lifestyle. Under low-energy (low-growth-rate) conditions, strain G20 further had the capacity to adapt to the metabolism of its methanogenic partners, as shown by its differing gene expression of enzymes involved in the direct metabolic interactions (e.g., periplasmic hydrogenases) and the ratio shift in electron carriers used for interspecies metabolite exchange (hydrogen/formate). A putative monomeric [Fe-Fe] hydrogenase and Hmc (high-molecular-weight-cytochrome c3) complex-linked reverse menaquinone (MQ) redox loop become increasingly important for the reoxidation of the lactate-/pyruvate oxidation-derived redox pair, DsrCred and Fdred, relative to the Qmo-MQ-Qrc (quinone-interacting membrane-bound oxidoreductase; quinone-reducing complex) loop. Together, these data underscore the high enzymatic and metabolic adaptive flexibility that likely sustains Desulfovibrio in naturally fluctuating methanogenic environments.
Demand Estimation For Agricultural Processing Co-Products

Co-products of processing agricultural commodities are often marketed through private transaction rather than through public markets or those in which public transaction information is recorded or available. The resulting lack of historical price information prohibits the use of positive time series techniques to estimate demand. Demand estimates for co-products are of value to both livestock producers, who obtain them for use in livestock rations, and processors, who must sell or otherwise dispose of them. Linear programming has long been used, first by researchers and later as a mainstream tool for nutritionists and producers, to formulate least-cost livestock rations. Here it is used as a normative technique to estimate step function demand schedules for co-products by individual livestock classes within a crop-reporting district. Regression is then used to smooth step function demand schedules by fitting demand data to generalized Leontief cost functions. Seemingly unrelated regression is used to estimate factor demand first adjusted for data censoring using probit analysis. Demand by individual livestock classes is aggregated over the number of livestock within a region. Quantities demanded by beef cows for each of the three co-products considered, sugarbeet pulp, wheat middlings, and potato waste, are large relative to other species because of their predominance in the district. At the current price for sugarbeet pulp, quantity demanded by district livestock is low. However quantity demanded is price elastic and becomes much greater at lower prices. Wheat middlings can be an important component of livestock rations, even at higher prices. At a price slightly below the current price, local livestock demand would exhaust the wheat middlings produced at the district's only wheat processing plant. Potato waste is most appropriate for ruminant diets because these animals are able to consume a large quantity of this high moisture feedstuff. Potato waste can be a cost-effective component in beef and dairy rations. Practically, livestock markets for potato waste must be in close proximity to a potato processing plant. Its high moisture content limits the distance it can be economically transported. At current prices, potato waste can be economically included in the ration for beef cows on a farm nearly 100 miles from the processing plant, although storage challenges may restrict use of the feed to closer operations.
Compliance: an over‐looked business strategy

Purpose - The purpose of this paper is to discuss the merits of self-regulation and the art of embedding it within an organisation, not as a secondary activity but as a core and fundamental business skill that ensures the survival of a business entity in the long term. Design/methodology/approach - The objective is achieved by considering compliance leadership as a strategy within a modern company. If the highest layer of stewardship of the firm (directors) explicitly accepts a conventional definition of business ethics (the law, best practice, a set of values in a specific hierarchy), then the author can measure this agreement and benchmark it against the highest known standards of corporate governance. Findings - Rational shareholders and managers will behave morally and find acceptable categorical imperatives to govern their behaviour. The delivery and preservation of long-term value demand that firms build capabilities to self-regulate and co-shape their environment, particularly if highly regulated. The paper suggests a way to organise the compliance leadership within some well-known business structures and present the idea that the chief executive officer of a firm who operates in a complex regulatory environment must make compliance a significant part if not the core element of his or her overall strategy. Research limitations/implications - Some arguments highlighting weaknesses in the Kantian arguments have not been fully discussed. A global initiative that measures the relationship between ethical maturity and share price has not been undertaken in the writing of this paper. Practical implications - Twenty-first century management must ensure the health and resilience of their company's culture to successfully manage and overcome the daily ethical questions that arise across all levels and layers of the organisation as a first priority and that whole business models can be built around this mission. Regulators should be accountable for recognising cultural crisis within the firms they regulate in order to balance the reliance on quantitative measurements of success and to navigate the complexity of the largest players in the market. Originality/value - The paper builds on earlier research by the author that rational norms of behaviour are core business capabilities that will produce industry leaders that can change the risk landscape of the industries wherein these firms operate. This new leadership will be demanded by the rational shareholder and will transform firms into stakeholder firms capable of interacting with their environment and creating and sustaining value over the longest term.
Enhanced Imperialist Competitive Algorithm for the Cell Formation Problem Using Sequence Data

Imperialist Competitive Algorithm (ICA) is a recent meta-heuristic method that is inspired by the social evolutions for solving NP-Hard problems. The ICA is a population-based algorithm which has achieved a great performance in comparison to other metaheuristics. This study is about developing enhanced ICA approach to solve the Cell Formation Problem (CFP) using sequence data. In addition to the conventional ICA, an enhanced version of ICA, namely EICA, applies local search techniques to add more intensification aptitude and embed the features of exploration and intensification more successfully. Suitable performance measures are used to compare the proposed algorithms with some other powerful solution approaches in the literature. In the same way, for checking the proficiency of algorithms, forty test problems are presented. Five benchmark problems have sequence data, and other ones are based on 0-1 matrices modified to sequence based problems. Computational results elucidate the efficiency of the EICA in solving CFP problems. Keywords—Cell formation problem, Group technology, Imperialist competitive algorithm, Sequence data.
Sectoral and Aggregate Inflation Dynamics in the Euro Area

This paper synthesises the implications of recent statistical evidence regarding inflation persistence in the euro area. For aggregate data, the degree of inflation persistence appears to be very high for sample periods spanning multiple decades but falls dramatically once we allow for time variation in the mean level of inflation; furthermore, the timing of these breaks in mean generally coincides with observed shifts in the monetary policy regime. Finally, sectoral inflation series exhibit much less persistence than aggregate inflation, mainly because of the influence of transitory sector-specific shocks. (JEL: E31, C22, C43) (c) 2006 by the European Economic Association.
Improving unbalanced downsampling via maximum spanning trees for graph signals

The state-of-the-art downsampling method for graph signals has been constructed by using maximum spanning trees (MSTs) of the graphs. For the graph signals defined on unweighted densely connected graphs, such as social network data, the sampling rates via MST-based downsampling are not close to 1 over 2, leading to a unbalanced downsampling phenomenon on multi-level downsampling. The unbalance hinders the applications of MST-based downsampling on constructing graph signal multiscale transforms, such as graph wavelet decomposition and multiscale pyramid transform. In this paper, we propose a simple but efficient method to improve the performance of the MST-based method on downsampling balance. For every graph signal, we first propose an unbalance possibility to measure the unbalance of the MST-based downsampling. If the unbalance possibility is high, the downsampling will be conducted on an improved MST, which is constructed by rearranging the structure of the MST to reduce the downsampling unbalance. The experiment results on synthesis graph signal show that the proposed improved MST leads to balanced downsampling. That is, the sampling rates produced by the improved MST are closer to 1 over 2 in multi-level downsampling than the original MST-based method.
Stochastic equity volatility related to the leverage effect II: valuation of European equity options and warrants

We propose a general framework to assess the value of the financial claims issued by the firm, European equity options and warrantsin terms of the stock price. In our framework, the firm's asset is assumed to follow a standard stationary lognormal process with constant volatility. However, it is not the case for equity volatility. The stochastic nature of equity volatility is endogenous, and comes from the impact of a change in the value of the firm's assets on the financial leverage. In a previous paper we studied the stochastic process for equity volatility, and proposed analytic approximations for different capital structures. In this companion paper we derive analytic approximations for the value of European equity options and warrants for a firm financed by equity, debt and warrants. We first present the basic model, which is an extension of the Black-Scholes model, to value corporate securities either as a function of the stock price, or as a function of the firm's total assets. Since stock prices are observable, then for practical purposes, traders prefer to use the stock as the underlying instrument, we concentrate on valuation models in terms of the stock price. Second, we derive an exact solution for the valuation in terms of the stock price of (i) a European call option on the stock of a levered firm, i.e. a European compound call option on the total assets of the firm, (ii) an equity warrant for an all-equity firm, and (iii) an equity warrant for a firm financed by equity and debt. Unfortunately, to compute these solutions we need to specify the function of the stock price in terms of the firm's assets value. In general we are unable to specify this expression, but we propose tight bounds for the value of these options which can be easily computed as a function of the stock price. Our results provide useful extensions of the Black-Scholes model.
Technology transfer offices and commercialization of university intellectual property: performance and policy implications

The recent increase in the rate of commercialization of intellectual property at US and European universities has important performance and policy implications. We review recent studies of the antecedents and consequences of these activities and then draw some lessons learned for policy-makers. A key conclusion is that universities and regions must formulate and implement coherent and feasible technology transfer/commercialization strategies.
Option Put-Call Parity Relations When the Underlying Security Pays Dividends

The original put-call parity relations hold under the premise that the underlying security does not pay dividends before the expiration of the options. Similar to Hull (2003), this paper relaxes the non-dividend-paying assumption. The underlying security price in the original European-style put-call parity relation is adjusted downwards by the present value of expected dividends before the option expires. The upper bound of the American-style put-call parity relation is adjusted upwards by the amount of the present value of expected dividends. The results provide theoretical boundaries of options prices and expand application of put-call parity relations to all options on currencies and dividend-paying stocks and stock indices, both European-style and American-style.
Soluble Robo4 receptor inhibits in vivo angiogenesis and endothelial cell migration

Roundabout receptors are molecular guidance molecules that function by interaction with Slit proteins to regulate axon guidance, neuronal migration, and leukocyte chemotaxis. We recently isolated a novel roundabout gene, called Robo4, which is restricted in expression to the endothelium, notably in areas of angiogenesis. The aim of this study was to use the soluble extracellular domain of Robo4 as a probe of function in angiogenesis and endothelial biology. Thus, the soluble extracellular domain of the receptor (Robo4Fc) showed diverse in vivo and in vitro activities including 1) inhibition of angiogenesis in vivo in the rodent subcutaneous sponge model, 2) inhibition of tube formation in the rat aortic ring assay, 3) inhibition of VEGF‐ and bFGF‐stimulated endothelial cell migration, and 4) inhibition of endothelial proliferation. To assess whether Robo4Fc was inhibiting Slit‐mediated effects, we determined whether Robo4 and Slit interact. Recombinant Slits‐1, ‐2, and ‐3 were shown by immunoprecipitation and BiaCore analysis to bind to Robo1 but not Robo4. Further study of the role of Robo4 in angiogenesis appears justified.
Performance measurement systems in the Finnish public sector

Purpose – This paper aims to identify the specific problems faced by the Finnish public sector organizations in designing and implementing performance measurement systems (PMS). Design/methodology/approach – An understanding of the problems is obtained by examining three case organizations in practice. In order to support the analysis of the empirical findings, a review of prior literature on the private and public sector PMSs is carried out.Findings – The design and implementation processes in the Finnish public sector organizations differ significantly from the way they are realized in industrial private sector companies. The four underlying reasons for problems in public sector organizations are the following: there are many stakeholders with conflicting needs; the end products and goals are undefined; there is a lack of property ownership and lacking management skills.Practical implications – By utilizing the results of the study, PMS design and implementation in the public sector can be carried out by.
You are AIRing too Much: Assessing the Privacy of Users in Crowdsourcing Environmental Data

With the availability of inexpensive sensors, the attractiveness of participatory sensing has increased tremendously in the last decade. However, when sensing is performed with devices owned by individuals, it raises several privacy issues with respect to the data producers, and hence reduces the incentive to contribute to the services. In this paper, we evaluate the extent to which a malicious server in a crowdsourcing air quality monitoring service can track the locations of users that contribute to the service. The participants periodically send information, such as temperature, relative humidity, carbon monoxide, and luminosity of their surrounding, using an off-the-shelf sensor connected to their mobile phones. The participants also send their coarse-grain location (i.e., disclosing the ID of the cell tower to which their mobile is coupled) along with the air quality data. We evaluate the precision with which the attacker can track the participants using only air quality data and location of the cell tower. We perform a thorough analysis of the privacy attack and show that it can accurately discover the destination of the users with a precision of more than 85% (up to 97%), if at least five consecutive samples are provided by the participants. We also discovered that the precision drops when the environmental sensors are affected by outside conditions (e.g., exposition to direct sunlight) but remains significant (54.5% for 20 consecutive samples).
The Fringes of Europe and EU Integration

Regions and cities in southern Europe are facing major problems in the present phase of European inte gration. Current changes in their spatial division of labour seem not to have been adequately understood by national and EU policy-makers as both are preoc cupied with the 'gap approach' and a linear view of the development process. Furthermore, the Maas tricht Treaty itself pays little attention to non- economic, non-competition issues in general and to urban and regional issues in particular. Southern fringes struggled a century ago for their integration into their national states and economies. For various historical reasons this project remained unfinished until the 1960s and 1970s. Now they have to start their struggle again under conditions of a zero-sum game in a culturally unknown environment.
Some behavioural considerations in the industrial location decision

Townroe P. M. (1972) Some behavioural considerations in the industrial location decision, Reg. Studies 6, 261–272. Behaviour patterns in the location decisions of a sample of 59 migrant manufacturing companies are related to the characteristics of the companies and of the moves. Chi-square tests are used to test for inter-relationships and a principal component analysis is applied to yield characteristic groups of companies. The results show great heterogeneity of behaviour and a wide divergence from an a priori pattern of “good management”.
Interface charge trapping and hot carrier reliability in high voltage SOI SJ LDMOSFET

This paper demonstrates and explains the effects of hot carrier injection and interface charge trapping correlated with impact ionization under normal on-state conditions in a highly dense low-resistance Super-Junction LDMOSFET. The study is done through extensive experimental measurements and numerical simulations using advanced trap models. The introduction of the SJ structure in the drift region of the LDMOSFET allows a shorter length and significantly higher drift doping both of which result in very low on-state resistance for a given breakdown voltage 170V. However careful design and optimization of the Super-junction layers is needed to avoid the combined effects of parastic JFET effect, impact ionization and charge trapping. The paper discusses these complex phenomena and gives solutions to increase robustness against instability problems.