Although the 2007 financial crisis, and the ensuing world-wide recession, has caused policy makers to want to 're-stabilize' the financial sector as well as 'rebalance' economies away from finance ...toward the 'real' economy, this article claims that to bring finance back to serve the real economy, it is fundamental to (a) also de-financialize companies in the real economy, and (b) think clearly how to structure finance so that it can provide the long-term committed patient capital required by innovation. Without this, the risk is that current policy produces a healthy financial sector (bailed out, ring-fenced, and re-structured) in a deeply sick economy, which continues to reward value extraction over value creation activities. PUBLICATION ABSTRACT
We report the discovery and analysis of a massive, compact, hierarchical triple system (TIC 470710327) initially identified by citizen scientists in data obtained by NASA’s Transiting Exoplanet ...Survey Satellite (TESS). Spectroscopic follow-up observations obtained with the HERMES spectrograph, combined with eclipse-timing variations (ETVs), confirm that the system is comprised of three OB stars, with a compact 1.10 d eclipsing binary and a non-eclipsing tertiary on a 52.04 d orbit. Dynamical modelling of the system (from radial velocity and ETVs) reveal a rare configuration wherein the tertiary star (O9.5-B0.5V; 14–17 Mꙩ) is more massive than the combined mass of the inner binary (10.9–13.2 Mꙩ). Given the high mass of the tertiary, we predict that this system will undergo multiple phases of mass transfer in the future, and likely end up as a double neutron star gravitational wave progenitor or an exotic Thorne–Żytkow object. Further observational characterization of this system promises constraints on both formation scenarios of massive stars as well as their exotic evolutionary end-products.
Platelet release by megakaryocytes is regulated by a concert of environmental and autocrine factors. We previously showed that constitutively released adenosine diphosphate by human megakaryocytes ...leads to platelet production. Here we show that adenosine diphosphate elicits, in human megakaryocytes, an increase in cytosolic calcium concentration, followed by a plateau, which is lowered in the absence of extracellular calcium, suggesting the involvement of Store-Operated Calcium Entry. Indeed, we demonstrate that megakaryocytes express the major candidates to mediate Store-Operated Calcium Entry, stromal interaction molecule 1, Orai1 and canonical transient receptor potential 1, which are activated upon either pharmacological or physiological depletion of the intracellular calcium pool. This mechanism is inhibited by phospholipase C or inositol-3-phosphate receptor inhibitors and by a specific calcium entry blocker. Studies on megakaryocyte behavior, on extracellular matrix proteins that support proplatelet extension, show that calcium mobilization from intracellular stores activates signaling cascades that trigger megakaryocyte adhesion and proplatelet formation, and promotes extracellular calcium entry which is primarily involved in the regulation of the contractile force responsible for megakaryocyte motility. These findings provide the first evidence that both calcium mobilization from intracellular stores and extracellular calcium entry specifically regulate human megakaryocyte functions.
Pre-slaughter transportation may affect poultry welfare and mortality rates. A retrospective analysis was conducted to examine the effect of environmental, management and individual factors on the ...percentage of dead birds during pre-slaughter transportation (dead-on-arrival, DOA). The variables accounted for in the analyses included: environmental temperature, travel duration, genetic line, gender, crate type and crate stocking density. Among the 41 452 loads of turkeys (34 696 388 birds) and 3241 of end of lay hens (21 788 124 birds) transported to three large abattoirs in northern Italy in a 3-year period, the median DOA was 0.14% in turkeys, and 0.38% in hens. In turkeys, travel duration longer than 30 min, temperature higher than 26°C and high in-crate densities were associated with increased DOA. In winter (⩽2°C), high stocking densities did not reduce the mortality risk from cold stress; on the contrary, for stocking densities either near to or just above the maximum density in EC Reg. 1/2005, the DOA risk was greater than for loads with densities of 10 kg/m2 less than the EC maximum. Male birds and specific genetic lines also showed a higher DOA. In hens, transportation lasting longer than 2 h and the brown-feathered breed were associated with higher DOA. Dead-on-arrival progressively increased with travel duration, remaining constant between 4 and 6 h and peaking at 8 h (median: 0.57%). The maximum DOA increase was detected during winter. These results show that several species-specific factors may lead to increased risk of mortality.
Abstract Background and aims Prediabetes increases cardiovascular risk and is associated with excess mortality. In preclinical models, metformin has been shown to exert anti-ageing effects. In this ...study, we sought to assess whether metformin modulates putative effector longevity programs in prediabetic subjects. Methods and results In a randomized, single-blind, placebo-controlled trial, 38 prediabetic subjects received metformin (1500 mg/day) or placebo for 2 months. At baseline and after treatment, we collected anthropometric and metabolic parameters. Gene and protein levels of SIRT1 , mTOR , p53 , p66Shc , SIRT1 activity, AMPK activation, telomere length, and SIRT1 promoter chromatin accessibility were determined in peripheral blood mononuclear cells (PBMCs). Plasma N-glycans, non-invasive surrogate markers of ageing, were also analysed. Compared to baseline, metformin significantly improved metabolic parameters and insulin sensitivity, increased SIRT1 gene/protein expression and SIRT1 promoter chromatin accessibility, elevated mTOR gene expression with concomitant reduction in p70S6K phosphorylation in subjects' PBMCs, and modified the plasma N-glycan profile. Compared to placebo, metformin increased SIRT1 protein expression and reduced p70S6K phosphorylation (a proxy of mTOR activity). Plasma N-glycans were also favourably modified by metformin compared to placebo. Conclusion In individuals with prediabetes, metformin ameliorated effector pathways that have been shown to regulate longevity in animal models. ClinicalTrials.gov Identifier NCT01765946 – January 2013.
Background and Objectives
The aim of our study was to test a platelet‐rich plasma releasate (PRP‐R/SRGF) from CaCl2‐activated platelets as a source of growth factors for the expansion of mesenchymal ...stromal cells (MSCs). PRP‐R/SRGF, obtained with a low‐cost procedure, is characterized by a reduced variability of growth factor release.
Materials and Methods
PRP‐R/SRGF is a clinical‐grade quality solution obtained from CaCl2‐activated platelets. Its activity was evaluated by measuring the proliferation, the phenotype, the differentiation potential and the immunosuppressive properties of MSCs derived from bone marrow (BM) and adipose tissue (AT).
Results
PRP‐R/SRGF was more active than FBS to expand BM‐ and AT‐derived MSCs. PRP‐R/SRGF treatment did not affect the expression of typical MSCs surface markers, neither MSCs differentiation potential nor their capability to inhibit activated T‐cell proliferation.
Conclusions
The clinical‐grade PRP‐R/SRGF may be used in the clinical setting for the expansion of MSCs.
The steep increase in human West Nile virus (WNV) infections in 2011–2012 in north-eastern Italy prompted a refinement of the surveillance plan. Data from the 2010–2012 surveillance activities on ...mosquitoes, equines, and humans were analysed through Bernoulli space–time scan statistics, to detect the presence of recurrent WNV infection hotspots. Linear models were fit to detect the possible relationships between WNV occurrence in humans and its activity in mosquitoes. Clusters were detected for all of the hosts, defining a limited area on which to focus surveillance and promptly identify WNV reactivation. Positive relationships were identified between WNV in humans and in mosquitoes; although it was not possible to define precise spatial and temporal scales at which entomological surveillance could predict the increasing risk of human infections. This stresses the necessity to improve entomological surveillance by increasing both the density of trapping sites and the frequency of captures.
Background and Objectives
Clinical use of plasma rich in growth factors requires biochemical product control. We aimed to measure and modulate concentrations of growth factors in solutions deriving ...from platelet apheresis or whole blood.
Materials and Methods
Growth factor concentrations were measured 5’, 10’, 20’, 30’, 60’ after CaCl2 was added at 40°C to platelet‐apheresis products (n = 39) or after 60’ in platelet concentrates from whole blood (n = 13). Growth factor release was also obtained in platelet apheresis a) by incubation at 22°C or 40°C for 10’ or 30’ (n = 4); b) by repeated freeze–thaw (n = 9).
Results
Fibroblast growth factor (FGF), platelet‐derived growth factor (PDGF) isoforms AA and AB and transforming growth factor beta (TGF‐β) concentrations (pg/109 plt) were 25–60% higher in growth factors solutions from whole blood compared to platelet apheresis. Vascular endothelial growth factor (VEGF), TGF‐β and PDGF isoforms were released early (5–10’) during incubation: TGF‐β concentration increased also at 30’. FGF and epidermal growth factor (EGF) were released only after 30’. Incubation at 40°C/10’ increased VEGF (+70%) and decreased EGF (−30%) and PDGF‐BB (−50%) versus 22°C/30’. Shock significantly increased TGF‐β (1·6‐fold), EGF (1·5‐fold), FGF (4·5‐fold) and lowered PDGF isoforms (0·2‐ to 0·5‐fold) versus prolonged incubation at 40°C.
Conclusion
Platelets from platelet apheresis and whole‐blood release all investigated growth factors. The release can be regulated controlling incubation time and/or temperature and performing cell lysis.
We present a framework, called the Risk-Reward Nexus, to study the relationship between innovation and inequality. We ask the following question: What types of economic actors (workers, taxpayers, ...shareholders) make contributions of effort and money to the innovation process for the sake of future, inherently uncertain, returns? Are these the same types of economic actors who are able to appropriate returns from the innovation process if and when they appear? That is, who takes the risks and who gets the rewards? We argue that it is the collective, cumulative, and uncertain characteristics of the innovation process that make this disconnect between risks and rewards possible. We conclude by sketching out key policy implications of the Risk-Reward Nexus approach. PUBLICATION ABSTRACT