Therapeutic Potential for Regulation of the Nuclear Factor Kappa-B Transcription Factor p65 to Prevent Cellular Senescence and Activation of Pro-Inflammatory in Mesenchymal Stem Cells

Mesenchymal stem cells have an important potential in the treatment of age-related diseases. In the last years, small extracellular vesicles derived from these stem cells have been proposed as cell-free therapies. Cellular senescence and proinflammatory activation are involved in the loss of therapeutic capacity and in the phenomenon called inflamm-aging. The regulators of these two biological processes in mesenchymal stem cells are not well-known. In this study, we found that p65 is activated during cellular senescence and inflammatory activation in human umbilical cord-derived mesenchymal stem cell. To demonstrate the central role of p65 in these two processes, we used small-molecular inhibitors of p65, such as JSH-23, MG-132 and curcumin. We found that the inhibition of p65 prevents the cellular senescence phenotype in human umbilical cord-derived mesenchymal stem cells. Besides, p65 inhibition produced the inactivation of proinflammatory molecules as components of a senescence-associated secretory phenotype (SASP) (interleukin-6 and interleukin-8 (IL-6 and IL-8)). Additionally, we found that the inhibition of p65 prevents the transmission of paracrine senescence between mesenchymal stem cells and the proinflammatory message through small extracellular vesicles. Our work highlights the important role of p65 and its inhibition to restore the loss of functionality of small extracellular vesicles from senescent mesenchymal stem cells and their inflamm-aging signature.     

Proteomics of plaques and novel sources of potential biomarkers for atherosclerosis

Cardiovascular disease (CVD) is the leading cause of death and loss of productive life years in the world. The underlying syndrome of CVD, atherosclerosis, is a complex disease process, which involves lipid metabolism, inflammation, innate and adaptive immunity, and many other pathophysiological aspects. Furthermore, CVD is influenced by genetic as well as environmental factors. Early detection of CVD and identification of patients at risk are crucial to reduce the burden of disease and to allow personalized treatment. As established risk factors fail to accurately predict which part of the population is likely to suffer from the disease, novel biomarkers are urgently needed. Proteomics can play a significant role in identifying these biomarkers. In this review, we describe the progress made in proteome profiling of the atherosclerotic plaque and several novel sources of potential biomarkers, including circulating cells and plasma extracellular vesicles. The importance of longitudinal biobanking in biomarker discovery is highlighted and exemplified by several plaque proteins identified in the biobank study Athero-Express. Finally, we discuss the PTMs of proteins that are involved in atherosclerosis, which may become one of the foci in the ongoing quest for biomarkers through proteomics of plaque and other matrices relevant to the progression of atherosclerosis.     

Marginal abatement costs of greenhouse gas emissions: A meta-analysis

In this paper, we carry out a meta-analysis of recent studies into the costs of greenhouse gas mitigation policies that aim at the long-term stabilisation of these gases in the atmosphere. We find the cost estimates of the studies to be sensitive to the stringency of the stabilisation target, the assumed emissions baseline, the way in which the time profile of emissions is determined in the model, the choice of control variable (CO₂ only versus multigas), the number of regions and energy sources in the model and, to a lesser degree, the scientific “forum” in which the study was developed. We find that marginal abatement costs of the stringent long-term targets that are currently considered by the European Commission are still very uncertain but might exceed the costs that have been suggested by recent policy assessments.     

Performance optimization of spectroscopic process analyzers

To increase the power and the robustness of spectroscopic process analyzers, methods are needed that suppress the spectral variation that is not related to the property of interest in the process stream. An approach for the selection of a suitable method is presented. The approach uses the net analyte signal (NAS) to analyze the situation and to select methods to suppress the nonrelevant spectral variation. The empirically determined signal-to-noise of the NAS is used as a figure of merit. The advantages of the approach are (i). that the error of the reference method does not affect method selection and (ii). that only a few spectral measurements are needed. A diagnostic plot is proposed that guides the user in the evaluation of the particular suppression method. As an example, NIR spectroscopic monitoring of a mol-sieve separation process is used.     

The M/G/1 queue with permanent customers

The authors examine an M/G/1 FCFS (first come, first served) queue with two types of customers: ordinary customers, who arrive according to a Poisson process, and permanent customers, who immediately return to the end of the queue after having received a service. The influence of the permanent customers on queue length and sojourn times of the Poisson customers is studied using results from queuing theory and from the theory of branching processes. In particular, it is shown that, when the service time distributions of the Poisson customers and all K permanent customers are negative exponential with identical means, the queue length and sojourn time distributions of the Poisson customers are the (K+1)-fold convolution of those for the case without permanent customers     

Rites of separation in strategic psychotherapy.

Points out that the creation and use of rituals is found in various aspects of the human experience. In strategic psychotherapy, rites of separation are used to aid clients in taking leave of the past. These rituals have a common structure, but their form and content vary according to the personality, needs, and experiences of clients. (23 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The Transboundary Impacts of Trade Liberalization and Climate Change on the Nile Basin Economies and Water Resource Availability

A multi-country, multi-sector computable general equilibrium (CGE) model is used for the first time to evaluate the economic and water resource availability effects of trade liberalization (removal of import tariffs) and facilitation (reducing non-tariff barriers) under climate change in the Nile Basin. The analysis uses the GTAP 9 Database and the GTAP-W model that distinguishes between rainfed and irrigated agriculture and implements water as a factor of production directly substitutable in the production process of irrigated agriculture. A full trade liberalization and improved trade facilitation scenario is considered with and without climate change. The study reveals that trade liberalization and facilitation generates substantial economic benefits and enhances economic growth and welfare in the Nile basin. The effect of instituting a free trade policy on water savings is found to be limited, while climate change improves water supply and hence irrigation water use, enhancing economic growth and welfare in the basin.     

Communicating (nature‐based) flood‐mitigation schemes using flood‐excess volume

As interest mounts in nature‐based solutions (NBS) for flood mitigation as complementary options to civil‐engineering measures, possible flood‐protection strategies have become more diverse and hence complicated to assess. We offer a straightforward and educational protocol targeted for effectiveness analysis and decision making involving stakeholder participation. It is based on the concept of flood‐excess volume (FEV), the volume exceeding a threshold and generating flood damage, and explores what fraction of FEV is reduced, and at what cost, by particular flood‐mitigation measures. Quantification and interpretation of cost scenarios are facilitated using a graphical display that is easy to understand and encapsulates concepts of flood magnitude, FEV and protection‐measures efficacy. It is exemplified for two recent extreme‐flood events on the River Calder in Mytholmroyd (Yorkshire, United Kingdom) and the River Brague in Biot (Alpes‐Maritimes, France). Each case has different flood‐mitigation measures such as natural water‐retention measures, tree planting, river‐bed widening, or use of reservoirs and floods walls. Our straightforward protocol enables fast, quantifiable and easy‐to‐understand exploration of protection strategies using multiple measures, and in doing so highlights the issue of NBS scalability.     

Study of a Classical Strobe Composition

Many strobe compositions were discovered in the past but only a few have been studied and none of them were fully understood. This article aimed at introducing the ternary composition of ammonium perchlorate as oxidizer, magnalium as fuel, and barium sulfate as metal salt. Parameters that influence its performances are analyzed. First, the binary compositions ammonium perchlorate/magnesium and ammonium perchlorate/magnalium were studied to observe the differences in behavior by using magnalium instead of magnesium. Next, variations were applied to the ternary composition changing the fuel: oxidizer:metal salt ratio. Finally the effect of potassium dichromate was analyzed. It is often added to the composition because it is known to improve the regularity and sharpness of flashes. The burning behavior was recorded using a high speed camera, together with emission spectra using a Charged‐Coupled Device (CCD) camera coupled with a spectrometer and the temporal evolution of the intensity with a photodiode coupled with an oscilloscope. The results of the experiment give first insights into the physical and chemical mechanisms and give directions to the further study on strobe reactions.     

Waiting-time approximations for cyclic-service systems with switchover times

Mean waiting-time approximations are derived for a single-server multi-queue system with nonexhaustive cyclic service. Nonzero switchover times of the server between consecutive queues are assumed. The main tool used in the derivation is a pseudo-conservation law recently found by Watson (1984). The approximation is simpler and, as extensive simulations show, more accurate than existing approximations. Moreover, it gives very good insight into the qualitative behaviour of cyclic-service queueing systems.