The construction of knowledge-based economies versus knowledge societies: The cases of Germany and Singapore

In the past decades, terms such as knowledge-based economy (KBE)\u27, and \u27information/knowledge society\u27 have been adopted by governments worldwide in order to underline their interest in developing their economies and societies further and assure future growth. Many governments used these catchwords as labels for government programs and action plans aiming at economic and social prosperity. This aim of national governments to construct knowledge-based economies, information/knowledge societies, the actions taken and especially the ability or disability to do so, is the topic of this paper. As two cases of comparison act Singapore and Germany. (DIPF/Orig.

Should the General Practitioner Consider Mesotherapy (Intradermal Therapy) to Manage Localized Pain?

Wide variations in the types of pain and response to analgesic pharmacotherapy mean that a variety of treatment strategies are needed. One approach is mesotherapy (intradermal therapy). This consists of microinjections into the skin and is ideally suited to the management of localized pain. Advantages include increasing the duration of drug activity, reduced risk of adverse events and interactions, and possible synergy with other therapies. Mesotherapy provides general practitioners with another tool for the treatment of local pain. However, it is important to provide patients with full details of the pros and cons of this approach and obtain informed patient consent

MECHANISMS OF DRUG-ESCAPE AND RELAPSE IN MULTIPLE MYELOMA: INTERPLAY BETWEEN ADAR1 AND NOTCH IN ABERRANT RNA EDITING

Multiple myeloma (MM) is a plasma cell malignancy that accounts for more than 10% of all blood cancers. Despite a wide variety of available lines of treatment, virtually all patients experience cycles of remission/relapse or become unresponsive to treatment. A growing body of evidence highlights the contribution of clonal heterogeneity to disease progression and resistance to therapy. In recent years the importance of post-transcriptional regulatory mechanisms (such as RNA editing) in cancer has emerged. RNA editing is particularly intriguing as a potential source of genetic diversity, as can affect several mRNA features, including stability, localization, nuclear retention, and alternative splicing. In mammals, most RNA editing is carried out by Adenosine Deaminases acting on dsRNA (ADAR) that catalyze the hydrolytic deamination of adenosines (A) to inosines (I). In particular, ADAR1 has been associated with disease progression and cancer stem cell maintenance in both solid tumors and hematopoietic malignancies. The central aim of this work was to investigate ADAR1 as a mechanism of clonal heterogeneity and drug resistance in MM. We postulated that ADAR1-dependent aberrant A-to-I RNA editing in MM cells could drive transcriptome \u201creprogramming\u201d in MM tumor cells, thus contributing to disease relapse and drug resistance. We also sought to identify cell-intrinsic and microenvironment-derived mechanisms that promote aberrant ADAR1-mediated RNA editing. We hypothesized that BM inflammatory signals, promoted by MM deregulated pathways such as Notch, sustain ADAR1-mediated reprogramming. We observed significantly increased ADAR1 expression in plasma cell leukemia (PCL), the advanced, highly drug-resistant stage of MM, and detected aberrant RNA editing in GLI1 and APOBEC3D transcripts by a novel RNA editing site-specific qPCR assay (RESSqPCR) that we developed. Furthermore, we established successful MM xenografts by intrahepatic transplantation of ADAR1-enriched PCL samples, thus providing a robust new in vivo model and platform for testing new therapeutic strategies aimed at treating drug-resistant forms of MM. We showed that continuous in vitro exposure to the anti-MM agent and immunomodulatory drug (IMiD), lenalidomide, induced ADAR1 expression and widespread aberrant RNA editing activity in MM cells, coupled with increased self-renewal capacity and a cancer stem cell phenotype. Furthermore, we observed that pro-inflammatory IL-6 promoted RNA editing, suggesting that MM-associated microenvironmental factors may play a key role in triggering ADAR1-associated malignant transcriptome recoding. Notably, IL-6 production from human BM stromal cells and from MM cells can be inhibited by silencing the overexpressed Notch ligands Jagged1 and Jagged2 in MM cells. In keeping with these findings, ADAR1 overexpression and deregulated RNA editing represents a unique source of RNA and protein diversity, and may endow survival advantages to MM cells in selective environments, such as the BM niche or under the pressure of chemotherapy. This work therefore identifies ADAR1 as a potential new diagnostic and therapeutic target in MM, and inhibition of this pathway, or its regulators and editing substrates, could provide a dynamic avenue to prevent disease relapse and disease progression and achieve long-term survival

Projecting the contribution of assisted reproductive technology to completed cohort fertility

Assisted reproductive technology (ART) is having an increasing influence on the fertility trends of high income countries characterised by a pattern of delayed childbearing. However, knowledge about the relationship between ART and completed fertility is limited and the extent to which delayed births are realized later in life through ART remains unexplored. Using data from Australian fertility clinics and national birth registries, the aim of this study is twofold: to project the contribution of ART for cohorts of women that have not yet completed their reproductive life; and to estimate the role played by ART in the fertility recuperation process. The proportion of children born after ART treatment is estimated to increase from 2.1% among women born in 1968 to 4.8-5.8% among women born in 1986. ART is projected to substantially affect the extent to which childbearing delay will be compensated at older ages, indicating that its availability may become an important factor in helping women to fulfil their reproductive plans later in life

Economic and environmental sustainability dimensions of a fashion supply chain: A quantitative model

Paper aim: The paper presents a model to assess the economic and the environmental sustainability dimensions of a fashion supply chain and tests it on a company. Originality: The gap intended to fill is the lack of models in this context having this purpose, and, in general, the necessity to develop models and metrics allowing to quantitatively assess the economic and environmental dimensions of supply chains. Research method: The fashion supply chain has been divided into five processes. Hence, an analytic model was developed by considering the total costs incurring in each process (economic evaluation), and the annual kilograms of CO2 emitted (environmental perspective). The model was then applied to a case study. Data was obtained from interviews with the management. Main findings: Results show that from the economic perspective supply impacts the most, while from the environmental one the most polluting activity is production. Implications for theory and practice: The model is easy to apply and to understand and allows to identify the activities in the supply chain where the majority of costs/emissions are generated. It is therefore expected to be useful for undertaking operational decisions aimed at decreasing the economic or environmental impact of a fashion supply chain

A model for assessing economic and environmental sustainability dimensions of a fashion supply chain and a case study

Due to the recent attention gained by sustainability issues in the context of supply chains, the aim of this study is to present a model developed under Microsoft Excel™ for the assessment of the economic and environmental dimensions of a fashion supply chain, sector that deserves particular attention being one of the most polluting in the world. The assessment of the economic dimension is made through the evaluation of the total cost incurred in each process of the supply chain, while the environmental aspect is evaluated in terms of the carbon dioxide emissions generated. Specifically, in this paper the modelling of the warehouse function is detailed. To test the effectiveness of the model a case study is carried out on a fashion company based in the North of Italy; the key results are reported in the manuscript, showing where the majority of costs and emissions are generated. Information obtained from this tool can support the company's management in their operational decisions and show where to focus their attention to enhance the economic and environmental sustainability

Chilled aeration to control pests and maintain grain quality during the summer storage of wheat in north central region of Kansas: Presentation

Chilled aeration allows to cool grain, independent of ambient conditions, to "safe" temperatures where insect, fungi, and spoilage is reduced to the minimum. The objective of this research was to evaluate the advantages of using grain chilling to preserve the quality of grain and reduce post-harvest losses, compared to conventional aeration and storage strategies used during the summer storage of wheat in Central Kansas, U.S.A. The research trials were developed in two 1,350 metric ton (t) steel silos in a Farmer’s Cooperative during the summer and fall of 2015 and 2016. One of the silos was chilled and the other was used as a control managed by the Cooperative. Variables evaluated were: grain temperature, moisture content (MC), grain quality, insect development and reproduction rate. The chilling treatment reduced the grain temperature from 28°C- 39°C to a minimum of 17°C- 17.6°C in less than 250 hours. Grain temperatures below 25°C were not possible during the summer using ambient aeration. Minimum variation of MC was observed in the Chilled silo while ambient aeration reduced the MC by 0.5%. Reproduction rates of RFB and LGB were significantly reduced by chilled temperatures lower than 17°C. Lower temperatures also reduced insects discovered in probe traps and insect damaged kernels (IDK). The energy cost of the grain chiller was between 0.26 US $/t- 0.32 US$/t higher than ambient aeration.Chilled aeration allows to cool grain, independent of ambient conditions, to "safe" temperatures where insect, fungi, and spoilage is reduced to the minimum. The objective of this research was to evaluate the advantages of using grain chilling to preserve the quality of grain and reduce post-harvest losses, compared to conventional aeration and storage strategies used during the summer storage of wheat in Central Kansas, U.S.A. The research trials were developed in two 1,350 metric ton (t) steel silos in a Farmer’s Cooperative during the summer and fall of 2015 and 2016. One of the silos was chilled and the other was used as a control managed by the Cooperative. Variables evaluated were: grain temperature, moisture content (MC), grain quality, insect development and reproduction rate. The chilling treatment reduced the grain temperature from 28°C- 39°C to a minimum of 17°C- 17.6°C in less than 250 hours. Grain temperatures below 25°C were not possible during the summer using ambient aeration. Minimum variation of MC was observed in the Chilled silo while ambient aeration reduced the MC by 0.5%. Reproduction rates of RFB and LGB were significantly reduced by chilled temperatures lower than 17°C. Lower temperatures also reduced insects discovered in probe traps and insect damaged kernels (IDK). The energy cost of the grain chiller was between 0.26 US $/t- 0.32 US$/t higher than ambient aeration

Investigation on the Performance of a Compact Three-Fluid Combined Membrane Contactor for Dehumidification in Electric Vehicles

In this paper, the performance of a compact Three-Fluid Combined Membrane Contactor (3F-CMC) is investigated using Computational Fluid Dynamics (CFD), supported and validated with a good agreement by an experimental campaign made on a fully working prototype. This internally-cooled membrane contactor is the core component of a hybrid air conditioning system for electric vehicles (EVs) developed in a successful H2020 project called XERIC. In the adopted numerical approach, the conjugate heat and mass transfer inside the 3F-CMC is described by non-isothermal incompressible flows and vapor transport through a PTFE hydrophobic membrane. The sensitivity of the 3F-CMC performance to air/desiccant flow rates, temperature, humidity, and desiccant concentration is analyzed numerically through the validated CFD codes. According to this study, the moisture removal increases by the inlet humidity ratio, nearly linearly. Under the considered conditions (where the inlet air temperature is 26.2C), when the inlet relative humidity (RH) is 75% the moisture removal is about 450% higher than the case RH = 37%, while the absorption effectiveness declines about 45%. Furthermore, this study shows that the amount of absorbed vapor flux rises by increasing the airflow rate; on the other hand, the higher the airflow rate, the lower is the overall absorption efficiency of the 3F-CMC. This investigation gives important suggestions on how to properly operate a 3F-CMC in order to achieve the requested performance, especially in hot and humid climates

Model cell membrane interaction with a bioinspired amphoteric polymer

We present recent investigation by means of nanoscale techniques on biocompatible linear polyamidoamines with amphoteric character, namely AGMA1 and ARGO7. These polymers have been shown of extremely promising and already proved medical interest, comprising their strong protection actions against virus infection, mainly papilloma and herpes and the extremely low toxicity of their DNA complexes, with respect to other used polymers such as PEI and protamine, applied in nanovector design for gene delivery. Our studies focus on the most important of these polymers, AGMA1, a prevailingly cationic 4-aminobutylguanidine-deriving PAA, whose mechanism of action is so far not fully understood. The current understanding is that its interaction with cell surfaces by means of glycosaminoglycans (HSPG) has a major role in its protective action against viruses. Yet, AGMA1 is active also against HPV-31, whose attachment does not appear to be dependent on HSPG. HPV-31, whose attachment does not appear to be dependent on HSPG. Therefore, AGMA1 binds other (as yet unidentified) receptors on the cell surface. As the known recipient is the HS carbohydrate moiety, other sugars rich membrane components have been proposed as probable AGMA1 target. Therefore, to shed a light on the mechanism of interaction of the polymer with sugar containing biologically relevant molecules, not HS, we have investigated AGMA1 in interaction with glycophyngolipids, Specifically, we studied multicomponent symmetric vesicles enriched in ganglioside GM1 built to mimic biological membrane domains, in the presence of AGMA1, At physiological pH, electrostatic effects should be the relevant interactions between GM1 and AGMA1. Taking advantage of the same mechanism we investigated the possibility of building lipid based core-shell particles to vehiculate AGMA1/siRNA complexes. Moreover, since it is probable that AGMA1 interacts with the barrier of mucus which cover the involved tissue we have extended our investigations also to mucin, constituting the biological barrier to the target tissues of the medical application of the polymers

Interaction of mucins with bioinspired polymers and drug delivery particles

Mucins are glycoproteins with high molecular weight and an abundance of negatively charged oligosaccharide side chains, representing the main components in the mucous gels apart from water. Mucin structure consists of a flexible backbone (mainly serine and threonine residues) which serves as anchoring points for oligosaccharide side chains, and hydrophobic \u201cnaked domains\u201d enriched in cysteine residues. The latter can form inter-molecular bonds via disulphide links, promoting mucin association in solution. Therefore, mucins can establish adhesive interactions with particulates/biomacromolecules via electrostatic interactions, van der Waals forces, hydrophobic forces, hydrogen bonding, or chain entanglement. Mucosal drug delivery vehicles can either penetrate rapidly or establish prolonged contact. However, their development is of great challenge because little is still known about the interactions between mucin and other macromolecules. We are currently working on a comprehensive study of the interaction between mucin and macromolecules of interest for pharmaceutical developments by complementary techniques. To this scope, we employ biocompatible natural and synthetic polymers with different physical-chemical characteristics. Among them, linear polyamidoamines with amphoteric character are particularly interesting for their cyto-biocompatibility. It is indeed crucial to characterise such interactions not only in the bulk but also at the interface, since complexation between mucins and biomacromolecules takes place close to the cell membrane surface. Moreover, the strategy to overcome mucus barrier and achieve long retention time in the cell surface is to develop nano-agents which can effectively penetrate the mucus layer and accumulate at the epithelial surface. In this framework we present preliminary investigations in the bulk by small angle x-ray scattering (SAXS) and at the solid-liquid interface by employing quartz crystal microbalance (QCM-D)