Inducible hydrogen sulfide synthesis in chondrocytes and mesenchymal progenitor cells: is H2S a novel cytoprotective mediator in the inflamed joint?

Hydrogen sulfide (H(2)S) has recently been proposed as an endogenous mediator of inflammation and is present in human synovial fluid. This study determined whether primary human articular chondrocytes (HACs) and mesenchymal progenitor cells (MPCs) could synthesize H(2)S in response to pro-inflammatory cytokines relevant to human arthropathies, and to determine the cellular responses to endogenous and pharmacological H(2)S. HACs and MPCs were exposed to IL-1β, IL-6, TNF-α and lipopolysaccharide (LPS). The expression and enzymatic activity of the H(2)S synthesizing enzymes cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE) were determined by Western blot and zinc-trap spectrophotometry, respectively. Cellular oxidative stress was induced by H(2)O(2), the peroxynitrite donor SIN-1 and 4-hydroxynonenal (4-HNE). Cell death was assessed by 3-(4,5-dimethyl-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. Mitochondrial membrane potential (DCm) was determined in situ by flow cytometry. Endogenous H(2) S synthesis was inhibited by siRNA-mediated knockdown of CSE and CBS and pharmacological inhibitors D,L-propargylglycine and aminoxyacetate, respectively. Exogenous H(2)S was generated using GYY4137. Under basal conditions HACs and MPCs expressed CBS and CSE and synthesized H(2)S in a CBS-dependent manner, whereas CSE expression and activity was induced by treatment of cells with IL-1β, TNF-α, IL-6 or LPS. Oxidative stress-induced cell death was significantly inhibited by GYY4137 treatment but increased by pharmacological inhibition of H(2)S synthesis or by CBS/CSE-siRNA treatment. These data suggest CSE is an inducible source of H(2)S in cultured HACs and MPCs. H(2)S may represent a novel endogenous mechanism of cytoprotection in the inflamed joint, suggesting a potential opportunity for therapeutic intervention.

Joint criminal enterprise

The doctrine of joint criminal enterprise is in disarray. Despite repeated judicial scrutiny at the highest level, the doctrine's scope, proper doctrinal basis and function in relation to other modes of complicity remain uncertain. This article examines the doctrine's elements and underlying principles. It argues that while joint criminal enterprise is largely used to make individuals liable for offences committed by their associates in excess of the common criminal purpose, its proper function is to police the limits of associate liability and thus to exculpate rather than inculpate. The doctrine governs not only instances of accessorial liability; it also applies where the parties involved are joint principal offenders. As this puts into question the prevalent view that joint criminal enterprise is a form of secondary participation that results in accessorial liability, the article concludes that it is best seen as a doctrine sui generis.

Premature impairment of methylation pathway and cardiac metabolic dysfunction in fa/fa obese Zucker rats

Increasing evidence suggests that obesity is a chronic inflammatory disease, in which adipose tissue is involved in a network of endocrine signals to modulate energy homeostasis. These oxidative-inflammatory pathways, which are associated with cardiovascular complications, are also observed during the aging process. In this study, we investigated the interaction between aging and the development of obesity in a hyperphagic rat model. Metabolic profiles of the liver, white adipose tissue (WAT) and heart from young and adult Zucker lean (fa/+) and obese (fa/fa) rats were characterized using a (1)H NMR-based metabonomics approach. We observed premature metabolic modifications in all studied organs in obese animals, some of which were comparable to those observed in adult lean animals. In the cardiac tissue, young obese rats displayed lower lactate and scyllo-inositol levels associated with higher creatine, choline and phosphocholine levels, indicating an early modulation of energy and membrane metabolism. An early alteration of the hepatic methylation and transsulfuration pathways in both groups of obese rats indicated that these pathways were affected before diabetic onset. These findings therefore support the hypothesis that obesity parallels some metabolic perturbations observed in the aging process and provides new insights into the metabolic modifications occurring in pre-diabetic state.

Joint compensation of multiple RF impairments in MIMO STBC systems

In this paper, we propose a compensation method for the joint effect of high-power amplifier (HPA) nonlinearity, in-phase/quadrature-phase (I/Q) imbalance and crosstalk in multiple-input multiple-output (MIMO) orthogonal space-time block coding (OSTBC) systems. The performance of the MIMO OSTBC equipped with the proposed compensation mechanism is evaluated in terms of average symbol error probability and system capacity, in Rayleigh fading channels. Numerical results are provided and show the effects on performance of several system parameters, namely, the HPA parameters, image-leakage ratio, crosstalk, numbers of antennas, and phase-shift keying modulation order.

Analysis and compensation for the joint effects of HPA nonlinearity, I/Q imbalance and crosstalk in MIMO beamforming systems

In this paper, we investigate the joint effects of high-power amplifier (HPA) nonlinearity, in-phase/quadrature-phase (I/Q) imbalance and crosstalk, on the performance of multiple-input multiple-output (MIMO) transmit beamforming (TB) systems, and propose a compensation method for the three impairments together. The performance of the MIMO TB system equipped with the proposed compensation scheme is evaluated in terms of average symbol error probability and capacity when transmissions are performed over uncorrelated Rayleigh fading channels. Numerical results are provided and show the effects on performance of several system parameters, namely, the HPA parameters, image-leakage ratio, crosstalk, numbers of antennas, length of pilot symbols and phase-shift keying modulation order.

The Joint UK Land Environment Simulator (JULES), model description – part 1: energy and water fluxes

This manuscript describes the energy and water components of a new community land surface model called the Joint UK Land Environment Simulator (JULES). This is developed from the Met Office Surface Exchange Scheme (MOSES). It can be used as a stand alone land surface model driven by observed forcing data, or coupled to an atmospheric global circulation model. The JULES model has been coupled to the Met Office Unified Model (UM) and as such provides a unique opportunity for the research community to contribute their research to improve both world-leading operational weather forecasting and climate change prediction systems. In addition JULES, and its forerunner MOSES, have been the basis for a number of very high-profile papers concerning the land-surface and climate over the last decade. JULES has a modular structure aligned to physical processes, providing the basis for a flexible modelling platform.

The joint influence of personal achievement goals and classroom goal structures on achievement-relevant outcomes

The authors provide an analytic framework for studying the joint influence of personal achievement goals and classroom goal structures on achievement-relevant outcomes. This framework encompasses 3 models (the direct effect model, indirect effect model, and interaction effect model), each of which addresses a different aspect of the joint influence of the 2 goal levels. These 3 models were examined together with a sample of 1,578 Japanese junior high and high school students from 47 classrooms. Results provided support for each of the 3 models: Classroom goal structures were not only direct, but also indirect predictors of intrinsic motivation and academic self-concept, and some cross-level interactions between personal achievement goals and classroom goal structures were observed (indicating both goal match and goal mismatch effects). A call is made for more research that takes into consideration achievement goals at both personal and structural levels of representation. (PsycINFO Database Record (c) 2012 APA, all rights reserved)(journal abstract)

An integrated multi-stage model of knowledge management in international joint ventures: identifying a trigger for knowledge exploration and knowledge harvest

This paper examines the evolution of knowledge management from the initial knowledge migration stage, through adaptation and creation, to the reverse knowledge migration stage in international joint ventures (IJVs). While many studies have analyzed these stages (mostly focusing on knowledge transfer), we investigated the path-dependent nature of knowledge flow in IJVs. The results from the empirical analysis based on a survey of 136 Korean parent companies of IJVs reveal that knowledge management in IJVs follows a sequential, multi-stage process, and that the knowledge transferred from parents to IJVs must first be adapted within its new environment before it reaches the creation stage. We also found that only created knowledge is transferred back to parents.

Plasma free fatty acids do not provide the link between obesity and insulin resistance or β-cell dysfunction: results of the Reading, Imperial, Surrey, Cambridge, Kings (RISCK) study

Aims To investigate the relationship between adiposity and plasma free fatty acid levels and the influence of total plasma free fatty acid level on insulin sensitivity and β-cell function. Methods An insulin sensitivity index, acute insulin response to glucose and a disposition index, derived from i.v. glucose tolerance minimal model analysis and total fasting plasma free fatty acid levels were available for 533 participants in the Reading, Imperial, Surrey, Cambridge, Kings study. Bivariate correlations were made between insulin sensitivity index, acute insulin response to glucose and disposition index and both adiposity measures (BMI, waist circumference and body fat mass) and total plasma free fatty acid levels. Multivariate linear regression analysis was performed, controlling for age, sex, ethnicity and adiposity. Results After adjustment, all adiposity measures were inversely associated with insulin sensitivity index (BMI: β = −0.357; waist circumference: β = −0.380; body fat mass: β = −0.375) and disposition index (BMI: β = −0.215; waist circumference: β = −0.248; body fat mass: β = −0.221) and positively associated with acute insulin response to glucose [BMI: β = 0.200; waist circumference: β = 0.195; body fat mass β = 0.209 (P values <0.001)]. Adiposity explained 13, 4 and 5% of the variation in insulin sensitivity index, acute insulin response to glucose and disposition index, respectively. After adjustment, no adiposity measure was associated with free fatty acid level, but total plasma free fatty acid level was inversely associated with insulin sensitivity index (β = −0.133), acute insulin response to glucose (β = −0.148) and disposition index [β = −0.218 (P values <0.01)]. Plasma free fatty acid concentration accounted for 1.5, 2 and 4% of the variation in insulin sensitivity index, acute insulin response to glucose and disposition index, respectively. Conclusions Plasma free fatty acid levels have a modest negative association with insulin sensitivity, β-cell secretion and disposition index but no association with adiposity measures. It is unlikely that plasma free fatty acids are the primary mediators of obesity-related insulin resistance or β-cell dysfunction.

Gaussian anamorphosis in the analysis step of the EnKF: a joint state-variable/observation approach

The analysis step of the (ensemble) Kalman filter is optimal when (1) the distribution of the background is Gaussian, (2) state variables and observations are related via a linear operator, and (3) the observational error is of additive nature and has Gaussian distribution. When these conditions are largely violated, a pre-processing step known as Gaussian anamorphosis (GA) can be applied. The objective of this procedure is to obtain state variables and observations that better fulfil the Gaussianity conditions in some sense. In this work we analyse GA from a joint perspective, paying attention to the effects of transformations in the joint state variable/observation space. First, we study transformations for state variables and observations that are independent from each other. Then, we introduce a targeted joint transformation with the objective to obtain joint Gaussianity in the transformed space. We focus primarily in the univariate case, and briefly comment on the multivariate one. A key point of this paper is that, when (1)-(3) are violated, using the analysis step of the EnKF will not recover the exact posterior density in spite of any transformations one may perform. These transformations, however, provide approximations of different quality to the Bayesian solution of the problem. Using an example in which the Bayesian posterior can be analytically computed, we assess the quality of the analysis distributions generated after applying the EnKF analysis step in conjunction with different GA options. The value of the targeted joint transformation is particularly clear for the case when the prior is Gaussian, the marginal density for the observations is close to Gaussian, and the likelihood is a Gaussian mixture.

Clonal expansion of early to mid-life mitochondrial DNA point mutations drives mitochondrial dysfunction during human ageing

Age-related decline in the integrity of mitochondria is an important contributor to the human ageing process. In a number of ageing stem cell populations, this decline in mitochondrial function is due to clonal expansion of individual mitochondrial DNA (mtDNA) point mutations within single cells. However the dynamics of this process and when these mtDNA mutations occur initially are poorly understood. Using human colorectal epithelium as an exemplar tissue with a well-defined stem cell population, we analysed samples from 207 healthy participants aged 17-78 years using a combination of techniques (Random Mutation Capture, Next Generation Sequencing and mitochondrial enzyme histochemistry), and show that: 1) non-pathogenic mtDNA mutations are present from early embryogenesis or may be transmitted through the germline, whereas pathogenic mtDNA mutations are detected in the somatic cells, providing evidence for purifying selection in humans, 2) pathogenic mtDNA mutations are present from early adulthood (<20 years of age), at both low levels and as clonal expansions, 3) low level mtDNA mutation frequency does not change significantly with age, suggesting that mtDNA mutation rate does not increase significantly with age, and 4) clonally expanded mtDNA mutations increase dramatically with age. These data confirm that clonal expansion of mtDNA mutations, some of which are generated very early in life, is the major driving force behind the mitochondrial dysfunction associated with ageing of the human colorectal epithelium.

State capitalism and social responsibility in China's banking industry

China’s financial system has experienced a series of major reforms in recent years. Efforts have been made towards introducing the shareholding system in state-owned commercial banks, restructuring of securities firms, re-organising equity of joint venture insurance companies, further improving the corporate governance structure, managing financial risks and ultimately establishing a system to protect investors (Xinhua, 2010). Financial product innovation, with the further opening up of financial markets and the development of the insurance and bond market, has increased liquidity as well as reduced financial risks. The U.S. subprime crisis indicated the benefit of financial innovations for the economy, but without proper control, they may lead to unexpected consequences. Kirkpatrick (2009) argues that failures and weaknesses in corporate governance arrangements and insufficient accounting standards and regulatory requirements attributed to the financial crisis. Similar to the financial crises of the last decade, the global financial crisis which sparked in 2008, surfaced a variety of significant corporate governance failures: the dysfunction of market mechanisms, the lack of transparency and accountability, misaligned compensation arrangements and the late response of government, all which encouraged management short-termism, poor risk management, as well as some fraudulent schemes. The unique characteristics of the Chinese banking system are an interesting point for studying post-crisis corporate governance reform. Considering that China modelled its governance system on the Anglo-American system, this paper examines the impact of the financial crisis on corporate governance reform in developed economies, and particularly, China’s reform of its financial sector. The paper further analyses the Chinese government’s role in bank supervision and risk management. In this regard, the paper contributes to the corporate governance literature within the Chinese context by providing insights into the contributing factors to the corporate governance failure that led to the global financial crisis. It also provides policy recommendations for China’s policy makers to seriously consider. The results suggest a need for the re-examination of corporate governance adequacy and the institutionalisation of business ethics. The paper’s next section provides a review of China’s financial system with reference to the financial crisis, followed by a critical evaluation of a capitalistic system and a review of Anglo-American and Continental European models. It then analyses the need for a new corporate governance model in China by considering the bank failures in developed economies and the potential risks and inefficiencies in a current State controlled system. The paper closes by reflecting the need for Chinese policy makers to continually develop, adapt and rewrite corporate governance practices capable of meeting the new challenge, and to pay attention to business ethics, an issue which goes beyond regulation.

Joint multiple dictionary learning for tensor sparse coding

Traditional dictionary learning algorithms are used for finding a sparse representation on high dimensional data by transforming samples into a one-dimensional (1D) vector. This 1D model loses the inherent spatial structure property of data. An alternative solution is to employ Tensor Decomposition for dictionary learning on their original structural form —a tensor— by learning multiple dictionaries along each mode and the corresponding sparse representation in respect to the Kronecker product of these dictionaries. To learn tensor dictionaries along each mode, all the existing methods update each dictionary iteratively in an alternating manner. Because atoms from each mode dictionary jointly make contributions to the sparsity of tensor, existing works ignore atoms correlations between different mode dictionaries by treating each mode dictionary independently. In this paper, we propose a joint multiple dictionary learning method for tensor sparse coding, which explores atom correlations for sparse representation and updates multiple atoms from each mode dictionary simultaneously. In this algorithm, the Frequent-Pattern Tree (FP-tree) mining algorithm is employed to exploit frequent atom patterns in the sparse representation. Inspired by the idea of K-SVD, we develop a new dictionary update method that jointly updates elements in each pattern. Experimental results demonstrate our method outperforms other tensor based dictionary learning algorithms.

JULES-crop: a parametrisation of crops in the Joint UK Land Environment Simulator

Studies of climate change impacts on the terrestrial biosphere have been completed without recognition of the integrated nature of the biosphere. Improved assessment of the impacts of climate change on food and water security requires the development and use of models not only representing each component but also their interactions. To meet this requirement the Joint UK Land Environment Simulator (JULES) land surface model has been modified to include a generic parametrisation of annual crops. The new model, JULES-crop, is described and evaluation at global and site levels for the four globally important crops; wheat, soybean, maize and rice. JULES-crop demonstrates skill in simulating the inter-annual variations of yield for maize and soybean at the global and country levels, and for wheat for major spring wheat producing countries. The impact of the new parametrisation, compared to the standard configuration, on the simulation of surface heat fluxes is largely an alteration of the partitioning between latent and sensible heat fluxes during the later part of the growing season. Further evaluation at the site level shows the model captures the seasonality of leaf area index, gross primary production and canopy height better than in the standard JULES. However, this does not lead to an improvement in the simulation of sensible and latent heat fluxes. The performance of JULES-crop from both an Earth system and crop yield model perspective is encouraging. However, more effort is needed to develop the parametrisation of the model for specific applications. Key future model developments identified include the introduction of processes such as irrigation and nitrogen limitation which will enable better representation of the spatial variability in yield.