Possible role for K+ in endothelium-derived hyperpolarizing factor–linked dilatation in rat middle cerebral artery

Background and Purpose— Endothelium-derived hyperpolarizing factor (EDHF) and K+ are vasodilators in the cerebral circulation. Recently, K+ has been suggested to contribute to EDHF-mediated responses in peripheral vessels. The EDHF response to the protease-activated receptor 2 ligand SLIGRL was characterized in cerebral arteries and used to assess whether K+ contributes as an EDHF. Methods— Rat middle cerebral arteries were mounted in either a wire or pressure myograph. Concentration-response curves to SLIGRL and K+ were constructed in the presence and absence of a variety of blocking agents. In some experiments, changes in tension and smooth muscle cell membrane potential were recorded simultaneously. Results— SLIGRL (0.02 to 20 μmol/L) stimulated concentration and endothelium-dependent relaxation. In the presence of NG-nitro-L-arginine methyl ester, relaxation to SLIGRL was associated with hyperpolarization and sensitivity to a specific inhibitor of IKCa, 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (1μmol/L), reflecting activation of EDHF. Combined inhibition of KIR with Ba2+ (30μmol/L) and Na+/K+-ATPase with ouabain (1 μmol/L) markedly attenuated the relaxation to EDHF. Raising extracellular [K+] to 15 mmol/L also stimulated smooth muscle relaxation and hyperpolarization, which was also attenuated by combined application of Ba2+ and ouabain. Conclusions— SLIGRL evokes EDHF-mediated relaxation in the rat middle cerebral artery, underpinned by hyperpolarization of the smooth muscle. The profile of blockade of EDHF-mediated hyperpolarization and relaxation supports a pivotal role for IKCa channels. Furthermore, similar inhibition of responses to EDHF and exogenous K+ with Ba2+ and ouabain suggests that K+ may contribute as an EDHF in the middle cerebral artery.

Inheritance, access to resources and poverty in Serer families in Senegal

This research explores the relationship between inheritance, access to resources and the intergenerational transmission of poverty among the Serer ethnic group in rural and urban environments in Senegal. In many Sub-Saharan African countries, customary law excludes women from owning and inheriting assets, such as land and property. Yet, assets controlled by women often result in increased investments in the next generation's health, nutrition and schooling and reduce the intergenerational transmission of poverty. Qualitative research with 60 participants in Senegal reveals the important role that land, housing and financial assets may play in building resilience to household shocks and interrupting the intergenerational transmission of poverty. However, the protection afforded by these assets was often dependent on other factors, including human, social and environmental capital. The death of a spouse or parent had major emotional and material impacts on many Serer families. The inheritance and control of assets and resources was strongly differentiated among family members along lines of gender, age and generation. Younger widows and their children were particularly vulnerable to chronic poverty. Although inheritance disputes were rare, the research suggests they are more likely between co-wives in polygamous unions and their children, particularly in urban areas. In addition to experiencing economic and health-related shocks, many interviewees were exposed to a range of climate-related risks and environmental pressures which increased their vulnerability. Family members coped with these shocks and risks by diversifying livelihoods, migrating to urban areas and other regions for work, participating in women's co-operatives and associations and developing supportive social networks with extended family and community members. Policies and practices that may help to alleviate poverty, safeguard women's and young people's inheritance and build resilience to financial, health-related and environmental shocks and risks include: - Social protection measures targeted towards poor widows and orphaned children, such as social and cash transfers to pay for basic needs including food, healthcare and children's schooling. - Micro-finance initiatives and credit and savings schemes, alongside training and capacity-building targeted to women and young people to develop income-generation activities and skills. - Free legal advice, support and advocacy for women and young people to pursue inheritance claims through the legal system. - Raising awareness about women's and children's legal rights and working with government and community and religious leaders to tackle discriminatory inheritance practices and contradictions caused by legal pluralism. - Increasing women's control of land and access to inputs, enhancing their business, organisational, and leadership skills and promoting civic participation in local, regional and national decision-making processes. - Improving access to basic services in rural areas, particularly healthcare, building the quality of education and promoting girls' access to education - Enhancing agricultural production and providing more employment opportunities, apprenticeships and vocational training for young people, particularly in rural areas.

Solvent-dependent modulation of metal–metal electronic interactions in a dinuclear cyanoruthenate complex: a detailed electrochemical, spectroscopic and computational study

The dinuclear complex [{Ru(CN)4}2(μ-bppz)]4− shows a strongly solvent-dependent metal–metal electronic interaction which allows the mixed-valence state to be switched from class 2 to class 3 by changing solvent from water to CH2Cl2. In CH2Cl2 the separation between the successive Ru(II)/Ru(III) redox couples is 350 mVand the IVCT band (from the UV/Vis/NIR spectroelectrochemistry) is characteristic of a borderline class II/III or class III mixed valence state. In water, the redox separation is only 110 mVand the much broader IVCT transition is characteristic of a class II mixed-valence state. This is consistent with the observation that raising and lowering the energy of the d(π) orbitals in CH2Cl2 or water, respectively, will decrease or increase the energy gap to the LUMO of the bppz bridging ligand, which provides the delocalisation pathway via electron-transfer. IR spectroelectrochemistry could only be carried out successfully in CH2Cl2 and revealed class III mixed-valence behaviour on the fast IR timescale. In contrast to this, time-resolved IR spectroscopy showed that the MLCTexcited state, which is formulated as RuIII(bppz˙−)RuII and can therefore be considered as a mixed-valence Ru(II)/Ru(III) complex with an intermediate bridging radical anion ligand, is localised on the IR timescale with spectroscopically distinct Ru(II) and Ru(III) termini. This is because the necessary electron-transfer via the bppz ligand is more difficult because of the additional electron on bppz˙− which raises the orbital through which electron exchange occurs in energy. DFT calculations reproduce the electronic spectra of the complex in all three Ru(II)/Ru(II), Ru(II)/Ru(III) and Ru(III)/Ru(III) calculations in both water and CH2Cl2 well as long as an explicit allowance is made for the presence of water molecules hydrogen-bonded to the cyanides in the model used. They also reproduce the excited-state IR spectra of both [Ru(CN)4(μ-bppz)]2– and [{Ru(CN)4}2(μ-bppz)]4− very well in both solvents. The reorganization of the water solvent shell indicates a possible dynamical reason for the longer life time of the triplet state in water compared to CH2Cl2.

Influence of probabilistic climate projections on building energy simulation

The Chartered Institute of Building Service Engineers (CIBSE) produced a technical memorandum (TM36) presenting research on future climate impacting building energy use and thermal comfort. One climate projection for each of four CO2 emissions scenario were used in TM36, so providing a deterministic outlook. As part of the UK Climate Impacts Programme (UKCIP) probabilistic climate projections are being studied in relation to building energy simulation techniques. Including uncertainty in climate projections is considered an important advance to climate impacts modelling and is included in the latest UKCIP data (UKCP09). Incorporating the stochastic nature of these new climate projections in building energy modelling requires a significant increase in data handling and careful statistical interpretation of the results to provide meaningful conclusions. This paper compares the results from building energy simulations when applying deterministic and probabilistic climate data. This is based on two case study buildings: (i) a mixed-mode office building with exposed thermal mass and (ii) a mechanically ventilated, light-weight office building. Building (i) represents an energy efficient building design that provides passive and active measures to maintain thermal comfort. Building (ii) relies entirely on mechanical means for heating and cooling, with its light-weight construction raising concern over increased cooling loads in a warmer climate. Devising an effective probabilistic approach highlighted greater uncertainty in predicting building performance, depending on the type of building modelled and the performance factors under consideration. Results indicate that the range of calculated quantities depends not only on the building type but is strongly dependent on the performance parameters that are of interest. Uncertainty is likely to be particularly marked with regard to thermal comfort in naturally ventilated buildings.

The potential inefficiency of using marketing margins in applied commodity price analysis, forecasting and risk management

This paper examines the implications of using marketing margins in applied commodity price analysis. The marketing-margin concept has a long and distinguished history, but it has caused considerable controversy. This is particularly the case in the context of analyzing the distribution of research gains in multi-stage production systems. We derive optimal tax schemes for raising revenues to finance research and promotion in a downstream market, derive the rules for efficient allocation of the funds, and compare the rules with an without the marketing-margin assumption. Applying the methodology to quarterly time series on the Australian beef-cattle sector and, with several caveats, we conclude that, during the period 1978:2 - 1988:4, the Australian Meat and Livestock Corporation optimally allocated research resources.

Ovarian expression of insulin-like peptide 3 (INSL3) and its receptor (RXFP2) during development of bovine antral follicles and corpora lutea and measurement of circulating INSL3 levels during synchronized estrous cycles

Insulin-like peptide 3 (INSL3), a major product of testicular Leydig cells, is also expressed by the ovary but its functional role remains poorly understood. Here, we quantified expression of INSL3 and its receptor RXFP2 in theca interna (TIC) and granulosa (GC) compartments of developing bovine antral follicles and in corpora lutea (CL). INSL3 and RXFP2 mRNA levels were much higher in TIC than GC and increased progressively during follicle maturation with INSL3 peaking in large (11-18mm) estrogen-active follicles and RXFP2 peaking in 9-10mm follicles before declining in larger (11-18mm) follicles. Expression of both INSL3 and RXFP2 in CL was much lower than in TIC. In situ hybridization and immunohistochemistry confirmed abundant expression of INSL3 mRNA and protein in TIC. These observations indicate follicular TIC rather than CL as the primary site of both INSL3 production and action, implying a predominantly auto-/paracrine role in TIC. To corroborate the above findings, we showed that in vitro exposure of TIC to a luteinizing concentration of LH greatly attenuated expression of both INSL3 and its receptor while increasing progesterone secretion and expression of STAR and CYP11A1. Moreover, in vivo, a significant cyclic variation in plasma INSL3 was observed during synchronized estrous cycles. INSL3 and estradiol-17β followed a similar pattern, both increasing after luteolysis, before falling sharply after the LH surge. Thus, theca-derived INSL3, likely from the dominant pre-ovulatory follicle, is detectable in peripheral blood of cattle and expression is down-regulated during luteinisation induced by the pre-ovulatory LH surge. Collectively, these findings underscore the likely role of INSL3 as an important intrafollicular modulator of TIC function/steroidogenesis, whilst raising doubts about its potential contribution to CL function.

Should kids pay their own way?

Children are expensive to raise. Ensuring that they are raised such that they are able to lead a minimally decent life costs time and money, and lots of both. Who is responsible for bearing the costs of the things that children are undoubtedly owed? This is a question that has received comparatively little scrutiny from political philosophers, despite children being such a drain on public and private finances alike. To the extent that there is a debate, two main views can be identified. The Parents Pay view says that parents, responsible for the existence of the costs, must foot the bill. The Society Pays view says that a next generation is a benefit to all, and so to allow parents to foot the bill alone is the worst kind of free-riding. In this paper, I introduce a third potentially liable party currently missing from the debate: children themselves. On my backward-looking view, we are entitled to ask people to contribute to the raising of children on the basis that they have benefited from being raised themselves.

L3 syntactic transfer selectivity and typological determinacy: the typological primacy model

The present article addresses the following question: what variables condition syntactic transfer? Evidence is provided in support of the position that third language (L3) transfer is selective, whereby, at least under certain conditions, it is driven by the typological proximity of the target L3 measured against the other previously acquired linguistic systems (cf. Rothman and Cabrelli Amaro, 2007, 2010; Rothman, 2010; Montrul et al., 2011). To show this, we compare data in the domain of adjectival interpretation between successful first language (L1) Italian learners of English as a second language (L2) at the low to intermediate proficiency level of L3 Spanish, and successful L1 English learners of L2 Spanish at the same levels for L3 Brazilian Portuguese. The data show that, irrespective of the L1 or the L2, these L3 learners demonstrate target knowledge of subtle adjectival semantic nuances obtained via noun-raising, which English lacks and the other languages share. We maintain that such knowledge is transferred to the L3 from Italian (L1) and Spanish (L2) respectively in light of important differences between the L3 learners herein compared to what is known of the L2 Spanish performance of L1 English speakers at the same level of proficiency (see, for example, Judy et al., 2008; Rothman et al., 2010). While the present data are consistent with Flynn et al.’s (2004) Cumulative Enhancement Model, we discuss why a coupling of these data with evidence from other recent L3 studies suggests necessary modifications to this model, offering in its stead the Typological Primacy Model (TPM) for multilingual transfer.

The creativity of action: Property, Kin and the social in African artisanal mining

Analyses of neo-liberal change in African mining tend to frame discussion through the lens of an overarching structural perspective. Far less attention has been paid to the way change is enacted within social relations in mining communities. To this end, our chapter considers how development in the Tanzanian mineral sector transforms people’s relationships and stimulates new iterations of power and agency within local trajectories of development, focusing on the case of artisanal gold mining in Mgusu village in Geita region, Tanzania. The aim is to trace how neo-liberal change configures market rationality and property relations in ways that can fundamentally alter social relationships within the local community, occupational groups and families, raising both opportunities for wealth accumulation and the potential to entrench poverty. The creative action involved in these processes generates new associational ties and repertoires of practice, as miners’ respond to change and the need to protect their livelihoods.

Palm oil, land rights and ecosystem services in Gbarpolu County, Liberia

As part of the rebuilding efforts following the long civil war, the Liberian government has renegotiated long-term contracts with international investors to exploit natural resources. Substantial areas of land have been handed out in large-scale concessions across Liberia during the last five years. While this may promote economic growth at the national level, such concessions are likely to have major environmental, social and economic impacts on local communities, who may not have been consulted on the proposed developments. This report examines the potential socio-economic and environmental impacts of a proposed large-scale oil palm concession in Bopolu District, Gbarpolu County in Liberia. The research provided an in-depth mapping of current resource use, livelihoods and ecosystems services, in addition to analysis of community consultation and perceptions of the potential impacts of the proposed development. This case study of a palm oil concession in Liberia highlights wider policy considerations regarding large-scale land acquisitions in the global South: • Formal mechanisms may be needed to ensure the process of Free, Prior, Informed Consent takes place effectively with affected communities and community land rights are safeguarded. • Rigorous Environmental and Social Impact Assessments need to be conducted before operations start. Accurate mapping of customary land rights, community resources and cultural sites, livelihoods, land use, biodiversity and ecosystems services is a critical tool in this process. • Greater clarity and awareness-raising of land tenure laws and policies is needed at all levels. Good governance and capacity-building of key institutions would help to ensure effective implementation of relevant laws and policies. • Efforts are needed to improve basic services and infrastructure in rural communities and invest in food crop cultivation in order to enhance food security and poverty alleviation. Increasing access to inputs, equipment, training and advice is especially important if male and female farmers are no longer able to practice shifting cultivation due to the reduction/ loss of customary land and the need to farm more intensively on smaller areas of land.

Separation of performance-approach and performance-avoidance achievement goals: A broader analysis

In the literature on achievement goals, performance-approach goals (striving to do better than others) and performance-avoidance goals (striving to avoid doing worse than others) tend to exhibit a moderate to high correlation, raising questions about whether the 2 goals represent distinct constructs. In the current article, we sought to examine the separability of these 2 goals using a broad factor-analytic approach that attended to issues that have been overlooked or underexamined in prior research. Five studies provided strong evidence for the separation of these 2 goal constructs: Separation was observed not only with exploratory factor analysis across different age groups and countries (Studies 1a and 1b) but also with change analysis (Study 2), ipsative factor analysis (Study 3), within-person analysis (Study 4), and behavioral genetics analysis (Study 5). We conclude by discussing the implications of the present research for the achievement goal literature, as well as the psychological literature in general.

Best practice in the training, appointment and remuneration of members of dispute boards for large infrastructure projects

This paper reports part of a qualitative study into evolving practice in the implementation of the Dispute Adjudication Board (DAB) construction dispute resolution technique, a variant of the Dispute Review Board (DRB) concept used in the US and Canada. Data was collected through a focus group interview of 20 highly experienced dispute resolution practitioners from engineering and the law. The group was assembled from members of FIDIC-NET with direct experience of project DABs. The part reported here concerns practice and procedure for establishing DABs. The main findings are that: constitution of the DABs is often delayed because of either project owners' ignorance of the DAB process or deterrence by the cost of the DABs; such owners also tend to insist on appointing DAB members from local engineers and lawyers without sufficient understanding of the DAB process; rates of remuneration of DAB members vary widely; the training provision for DAB membership and advocacy skills is inadequate; the process of selecting candidates for DAB membership and negotiating the tripartite agreement between each member and the contractual parties needs to be navigated with great care to avoid raising ethical problems. The research contribution is threefold. First, it highlights the importance of realistic fees for DAB members within a standard framework in achieving timely establishment of a board that works well as a team. Second, it illustrates the use of qualitative focus group interview to study the impact of new contract terms from multiple stakeholder perspectives. Finally, it identifies areas where further research is needed.

Research practices that can prevent an inflation of false-positive rates

Recent studies have indicated that research practices in psychology may be susceptible to factors that increase false-positive rates, raising concerns about the possible prevalence of false-positive findings. The present article discusses several practices that may run counter to the inflation of false-positive rates. Taking these practices into account would lead to a more balanced view on the false-positive issue. Specifically, we argue that an inflation of false-positive rates would diminish, sometimes to a substantial degree, when researchers (a) have explicit a priori theoretical hypotheses, (b) include multiple replication studies in a single paper, and (c) collect additional data based on observed results. We report findings from simulation studies and statistical evidence that support these arguments. Being aware of these preventive factors allows researchers not to overestimate the pervasiveness of false-positives in psychology and to gauge the susceptibility of a paper to possible false-positives in practical and fair ways.

High density lipoproteins (HDLs) and atherosclerosis; the unanswered questions

The concentration of high density lipoprotein-cholesterol (HDL-C) has been found consistently to be a powerful negative predictor of premature coronary heart disease (CHD) in human prospective population studies. There is also circumstantial evidence from human intervention studies and direct evidence from animal intervention studies that HDLs protect against the development of atherosclerosis. HDLs have several documented functions, although the precise mechanism by which they prevent atherosclerosis remains uncertain. Nor is it known whether the cardioprotective properties of HDL are specific to one or more of the many HDL subpopulations that comprise the HDL fraction in human plasma. Several lifestyle and pharmacological interventions have the capacity to raise the level of HDL-C, although it is not known whether all are equally protective. Indeed, despite the large body of information identifying HDLs as potential therapeutic targets for the prevention of atherosclerosis, there remain many unanswered questions that must be addressed as a matter of urgency before embarking wholesale on HDL-C-raising therapies as strategies to prevent CHD. This review summarises what is known and highlights what we still need to know.

Protection of dried probiotic bacteria from bile using bile adsorbent resins

Enteric coated oral tablets or capsules can deliver dried live cells directly into the intestine. Previously, we found that a live attenuated bacterial vaccine acquired sensitivity to intestinal bile when dried, raising the possibility that although gastric acid can be bypassed, significant loss of viability might occur on release from an enteric coated oral formulations. Here we demonstrate that some food-grade lyophilised preparations of Lactobacillus casei and Lactobacillus salivarius also show temporary bile sensitivity that can be rapidly reversed by rehydration. To protect dried bacterial cells from temporary bile sensitivity, we propose using bile acid adsorbing resins, such as cholestyramine, which are bile acid binding agents, historically used to lower cholesterol levels. Vcaps™ HPMC capsules alone provided up to 830-fold protection from bile. The inclusion of 50% w/w cholestyramine in Vcaps™ HPMC capsules resulted in release of up to 1700-fold more live Lactobacillus casei into simulated intestinal fluid containing 1% bile, when compared to dried cells added directly to bile. We conclude that delivery of dried live probiotic organisms to the intestine may be improved by providing protection from bile by addition of bile adsorbing resins and the use of HPMC capsules.