Is there excess co-movement of primary commodity prices? A co-integration test

It is a common perception that primary commodity prices tend to move together. This perception is especially common among commodity traders who may justify an increase in the price of one commodity because the prices of other commodities have increased. This commodity price co-movement can be identified among commodities that seem unrelated in terms of production or consumption substitutability or complementarity. But there is no reason for believing that prices of unrelated commodities should move together, except for macroeconomic shocks affecting commodity markets in general. For example, in a recession commodity prices decline across the board because demand declines; and in periods of generalinflation commodity prices rise, partly because commodities provide a hedge against inflation. However, after accounting for macroeconomic shocks, is co-movement among prices still evident? In this paper, the authors test for co-movement and excess co-movement of primary commodity prices using the econometric tests of co-integration in time series and the resulting error-correction models (ECM). The ECMs will be used to examine the existence of short-run excess co-movement between commodity prices, taking into consideration the long-run relationship between them.Crops&Crop Management Systems,Environmental Economics&Policies,Montreal Protocol,Markets and Market Access,Access to Markets

Shear Strength of Lightly Reinforced T-Beams

Fifteen lightly reinforced concrete T-beams, 11 with stirrups and four without stirrups, were tested to failure. The major variables rit the study were the amounts of flexural and shear reinforcement. The flexural steel varied from 0.5 to 1 percent, and the shear reinforcement varied from 0 to 110 psi (0.75 MPa). The test results are analyzed and compared with the shear design provisions of "Building Code Requirements for Reinforced Concrete (AC1 318-77)" and the recommendations of AC1 Committee 426, Shear and Diagonal Tension. The test results confirmed the findings of other investigators, that the present AC1 equations for the shear cracking load are unconservative for beams without stirrups, having a longitudinal reinforcing ratio less than 1 percent. However, for beams with stirrups the web reinforcement was 1.5 times as effective as predicted by AC1 318-77 and compensated for the lower shear strength of the concrete. It is recommended that the shear design provisions of AC1 318-77 be retained in their current form

Indicators for mapping and assessment of ecosystem condition and of the ecosystem service habitat maintenance in support of the EU Biodiversity Strategy to 2020

A systematic approach to map and assess the “maintenance of nursery populations and habitats” ecosystem service (ES) (hereinafter called “habitat maintenance”) has not yet emerged. In this article, we present an ecosystem service framework implementation at landscape level, by proposing an approach for calculating and combining a series of indicators with spatial modelling techniques. Necessary conceptual elements for this approach are: a) ecosystem condition, b) supply and demand of the targeted ecosystem service and c) spatial relationships between the Service Providing Units (SPU) and the Service Connecting Units (SCU). Ecosystem condition is quantified and mapped based on two indicators, the Biodiversity State and the Anthropogenic Impact. Quantification and mapping of supply and demand are based on the hypothesis that high supply can be activated in strictly protected areas and that a demand is localised in the Natura 2000 sites (N2K), considering them as the Service Benefit Areas (SBA). Wetlands are assessed as SCU between the SBA and the landscape areas where the habitat maintenance ES is supplied. By assessing wetlands as SCU, we intent to highlight their role as biodiversity stepping stones and as green infrastructures. Overall, we conclude that the EU biodiversity policy demand for no net loss and for a coherent N2K network can be met by enhancing the delivery of the habitat maintenance ES. This approach can assist policy-makers in prioritisation of conservation and restoration targets, in line with the EU biodiversity strategy to 2020 and the preparation of the post-2020 Strategy. One Ecosystem 4: e32704. https://doi.org/10.3897/oneeco.4.e3270

Premature Senescence and Cardiovascular Disease Following Cancer Treatments: Mechanistic Insights

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality, especially among the aging population. The response-to-injury model proposed by Dr. Russell Ross in 1999 emphasizes inflammation as a critical factor in atherosclerosis development, with atherosclerotic plaques forming due to endothelial cell (EC) injury, followed by myeloid cell adhesion and invasion into the blood vessel walls. Recent evidence indicates that cancer and its treatments can lead to long-term complications, including CVD. Cellular senescence, a hallmark of aging, is implicated in CVD pathogenesis, particularly in cancer survivors. However, the precise mechanisms linking premature senescence to CVD in cancer survivors remain poorly understood. This article aims to provide mechanistic insights into this association and propose future directions to better comprehend this complex interplay

An ERK5-NRF2 Axis Mediates Senescence-Associated Stemness and Atherosclerosis

BACKGROUND: ERK5 (extracellular signal-regulated kinase 5) is a dual kinase transcription factor containing an N-terminal kinase domain and a C-terminal transcriptional activation domain. Many ERK5 kinase inhibitors have been developed and tested to treat cancer and inflammatory diseases. However, recent data have raised questions about the role of the catalytic activity of ERK5 in proliferation and inflammation. We aimed to investigate how ERK5 reprograms myeloid cells to the proinflammatory senescent phenotype, subsequently leading to atherosclerosis. METHODS: A ERK5 S496A (dephosphorylation mimic) knock in (KI) mouse model was generated using CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat-associated 9), and atherosclerosis was characterized by hypercholesterolemia induction. The plaque phenotyping in homozygous ERK5 S496A KI and wild type (WT) mice was studied using imaging mass cytometry. Bone marrow-derived macrophages were isolated from hypercholesterolemic mice and characterized using RNA sequencing and functional in vitro approaches, including senescence, mitochondria reactive oxygen species, and inflammation assays, as well as by metabolic extracellular flux analysis. RESULTS: We show that atherosclerosis was inhibited in ERK5 S496A KI mice. Furthermore, ERK5 S496 phosphorylation mediates both senescence-associated secretory phenotype and senescence-associated stemness by upregulating AHR (aryl hydrocarbon receptor) in plaque and bone marrow-derived macrophages isolated from hypercholesterolemic mice. We also discovered that ERK5 S496 phosphorylation could induce NRF2 (NFE2-related factor 2) SUMOylation at a novel K518 site to inhibit NRF2 transcriptional activity without altering ERK5 catalytic activity and mediates oxidized LDL (low-density lipoprotein)-induced senescence-associated secretory phenotype. Specific ERK5 kinase inhibitors (AX15836 and XMD8-92) also inhibited ERK5 S496 phosphorylation, suggesting the involvement of ERK5 S496 phosphorylation in the anti-inflammatory effects of these ERK5 kinase inhibitors. CONCLUSIONS: We discovered a novel mechanism by which the macrophage ERK5-NRF2 axis develops a unique senescence-associated secretory phenotype/stemness phenotype by upregulating AHR to engender atherogenesis. The finding of senescence-associated stemness phenotype provides a molecular explanation to resolve the paradox of senescence in proliferative plaque by permitting myeloid cells to escape the senescence-induced cell cycle arrest during atherosclerosis formation

Determining PTEN Functional Status by Network Component Deduced Transcription Factor Activities

PTEN-controlled PI3K-AKT-mTOR pathway represents one of the most deregulated signaling pathways in human cancers. With many small molecule inhibitors that target PI3K-AKT-mTOR pathway being exploited clinically, sensitive and reliable ways of stratifying patients according to their PTEN functional status and determining treatment outcomes are urgently needed. Heterogeneous loss of PTEN is commonly associated with human cancers and yet PTEN can also be regulated on epigenetic, transcriptional or post-translational levels, which makes the use of simple protein or gene expression-based analyses in determining PTEN status less accurate. In this study, we used network component analysis to identify 20 transcription factors (TFs) whose activities deduced from their target gene expressions were immediately altered upon the re-expression of PTEN in a PTEN-inducible system. Interestingly, PTEN controls the activities (TFA) rather than the expression levels of majority of these TFs and these PTEN-controlled TFAs are substantially altered in prostate cancer mouse models. Importantly, the activities of these TFs can be used to predict PTEN status in human prostate, breast and brain tumor samples with enhanced reliability when compared to straightforward IHC-based or expression-based analysis. Furthermore, our analysis indicates that unique sets of PTEN-controlled TFAs significantly contribute to specific tumor types. Together, our findings reveal that TFAs may be used as “signatures” for predicting PTEN functional status and elucidate the transcriptional architectures underlying human cancers caused by PTEN loss

MYC functions are specific in biological subtypes of breast cancer and confers resistance to endocrine therapy in luminal tumours.

BACKGROUND: MYC is amplified in approximately 15% of breast cancers (BCs) and is associated with poor outcome. c-MYC protein is multi-faceted and participates in many aspects of cellular function and is linked with therapeutic response in BCs. We hypothesised that the functional role of c-MYC differs between molecular subtypes of BCs. METHODS: We therefore investigated the correlation between c-MYC protein expression and other proteins involved in different cellular functions together with clinicopathological parameters, patients' outcome and treatments in a large early-stage molecularly characterised series of primary invasive BCs (n=1106) using immunohistochemistry. The METABRIC BC cohort (n=1980) was evaluated for MYC mRNA expression and a systems biology approach utilised to identify genes associated with MYC in the different BC molecular subtypes. RESULTS: High MYC and c-MYC expression was significantly associated with poor prognostic factors, including grade and basal-like BCs. In luminal A tumours, c-MYC was associated with ATM (P=0.005), Cyclin B1 (P=0.002), PIK3CA (P=0.009) and Ki67 (P<0.001). In contrast, in basal-like tumours, c-MYC showed positive association with Cyclin E (P=0.003) and p16 (P=0.042) expression only. c-MYC was an independent predictor of a shorter distant metastases-free survival in luminal A LN+ tumours treated with endocrine therapy (ET; P=0.013). In luminal tumours treated with ET, MYC mRNA expression was associated with BC-specific survival (P=0.001). In ER-positive tumours, MYC was associated with expression of translational genes while in ER-negative tumours it was associated with upregulation of glucose metabolism genes. CONCLUSIONS: c-MYC function is associated with specific molecular subtypes of BCs and its overexpression confers resistance to ET. The diverse mechanisms of c-MYC function in the different molecular classes of BCs warrants further investigation particularly as potential therapeutic targets