Effects of temperature, ammonium and glucose concentrations on yeast growth in a model wine system

In enology, alcoholic fermentation is a complex process involving several mechanisms. Slow and incomplete alcoholic fermentation is a chronic problem for the wine industry and factors leading to sluggish and stuck fermentations have been extensively studied and reviewed. The most studied cause of sluggish and stuck fermentation is the nitrogen content limitation. Nevertheless, other factors, such as temperature of fermentation and sugar concentration can affect the growth of yeasts. In this study we modelled the yeast growth‐cycle in wine model system as a function of temperature, sugar and ammonium concentrations; the individual effects and the interaction of these factors were analysed by means of a quadratic response surface methodology. Cell concentrations and weight loss were monitored in the whole wine fermentation process. The results of central composite design show that lower is the availability of nitrogen, higher is the cell growth rate; moreover, initial nitrogen concentration also influences survival time of Saccharomyces cerevisiae.     

DYRE: a DYnamic REconfigurable solution to increase GPGPU’s reliability

The Journal of Supercomputing - General-purpose graphics processing units (GPGPUs) are extensively used in high-performance computing. However, it is well known that these devices’...     

Decision making with a fuzzy ontology

Knowledge mobilisation is a transition from the prevailing knowledge management technology that has been widely used in industry for the last 20?years to a new methodology and some innovative methods for knowledge representation, formation and development and for knowledge retrieval and distribution. Knowledge mobilisation aims at coming to terms with some of the problems of knowledge management and at the same time to introduce new theory, new methods and new technology. More precisely, this paper presents an outline of a fuzzy ontology as an enhanced version of classical ontology and demonstrates some advantages for practical decision making. We show that a number of soft computing techniques, e.g. aggregation functions and interval valued fuzzy numbers, will support effective and practical decision making on the basis of the fuzzy ontology. We demonstrate the knowledge mobilisation methods with the construction of a support system for finding the best available wine for a number of wine drinking occasions using a fuzzy wine ontology and fuzzy reasoning methods; the support system has been implemented for a Nokia N900 smart phone.     

Adaptive course generation through learning styles representation

This paper presents an approach to automatic course generation and student modeling. The method has been developed during the European funded projects Diogene and Intraserv, focused on the construction of an adaptive e-learning platform. The aim of the platform is the automatic generation and personalization of courses, taking into account pedagogical knowledge on the didactic domain as well as statistic information on both the student’s knowledge degree and learning preferences. Pedagogical information is described by means of an innovative methodology suitable for effective and efficient course generation and personalization. Moreover, statistic information can be collected and exploited by the system in order to better describe the student’s preferences and learning performances. Learning material is chosen by the system matching the student’s learning preferences with the learning material type, following a pedagogical approach suggested by Felder and Silverman. The paper discusses how automatic learning material personalization makes it possible to facilitate distance learning access to both able-bodied and disabled people. Results from the Diogene and Intraserv evaluation are reported and discussed.     

Platelet-Derived miR-126-3p Directly Targets AKT2 and Exerts Anti-Tumor Effects in Breast Cancer Cells: Further Insights in Platelet-Cancer Interplay

Among the surrounding cells influencing tumor biology, platelets are recognized as novel players as they release microvesicles (MVs) that, once delivered to cancer cells, modulate signaling pathways related to cell growth and dissemination. We have previously shown that physiological delivery of platelet MVs enriched in miR-126 exerted anti-tumor effects in different breast cancer (BC) cell lines. Here, we seek further insight by identifying AKT2 kinase as a novel miR-126-3p direct target, as assessed by bioinformatic analysis and validated by luciferase assay. Both ectopic expression and platelet MV-mediated delivery of miR-126-3p downregulated AKT2 expression, thus suppressing proliferating and invading properties, in either triple negative (BT549 cells) or less aggressive Luminal A (MCF-7 cells) BC subtypes. Accordingly, as shown by bioinformatic analysis, both high miR-126 and low AKT2 levels were associated with favorable long-term prognosis in BC patients. Our results, together with the literature data, indicate that miR-126-3p exerts suppressor activity by specifically targeting components of the PIK3/AKT signaling cascade. Therefore, management of platelet-derived MV production and selective delivery of miR-126-3p to tumor cells may represent a useful tool in multimodal therapeutic approaches in BC patients.     

Characterisation of Progressive Skeletal Muscle Fibrosis in the Mdx Mouse Model of Duchenne Muscular Dystrophy: An In Vivo and In Vitro Study

Duchenne muscular dystrophy (DMD) is a rare genetic disease leading to progressive muscle wasting, respiratory failure, and cardiomyopathy. Although muscle fibrosis represents a DMD hallmark, the organisation of the extracellular matrix and the molecular changes in its turnover are still not fully understood. To define the architectural changes over time in muscle fibrosis, we used an mdx mouse model of DMD and analysed collagen and glycosaminoglycans/proteoglycans content in skeletal muscle sections at different time points during disease progression and in comparison with age-matched controls. Collagen significantly increased particularly in the diaphragm, quadriceps, and gastrocnemius in adult mdx, with fibrosis significantly correlating with muscle degeneration. We also analysed collagen turnover pathways underlying fibrosis development in cultured primary quadriceps-derived fibroblasts. Collagen secretion and matrix metalloproteinases (MMPs) remained unaffected in both young and adult mdx compared to wt fibroblasts, whereas collagen cross-linking and tissue inhibitors of MMP (TIMP) expression significantly increased. We conclude that, in the DMD model we used, fibrosis mostly affects diaphragm and quadriceps with a higher collagen cross-linking and inhibition of MMPs that contribute differently to progressive collagen accumulation during fibrotic remodelling. This study offers a comprehensive histological and molecular characterisation of DMD-associated muscle fibrosis; it may thus provide new targets for tailored therapeutic interventions.     

Primary Aldosteronism and Resistant Hypertension: A Pathophysiological Insight

Primary aldosteronism (PA) is a pathological condition characterized by an excessive aldosterone secretion; once thought to be rare, PA is now recognized as the most common cause of secondary hypertension. Its prevalence increases with the severity of hypertension, reaching up to 29.1% in patients with resistant hypertension (RH). Both PA and RH are “high-risk phenotypes”, associated with increased cardiovascular morbidity and mortality compared to non-PA and non-RH patients. Aldosterone excess, as occurs in PA, can contribute to the development of a RH phenotype through several mechanisms. First, inappropriate aldosterone levels with respect to the hydro-electrolytic status of the individual can cause salt retention and volume expansion by inducing sodium and water reabsorption in the kidney. Moreover, a growing body of evidence has highlighted the detrimental consequences of “non-classical” effects of aldosterone in several target tissues. Aldosterone-induced vascular remodeling, sympathetic overactivity, insulin resistance, and adipose tissue dysfunction can further contribute to the worsening of arterial hypertension and to the development of drug-resistance. In addition, the pro-oxidative, pro-fibrotic, and pro-inflammatory effects of aldosterone may aggravate end-organ damage, thereby perpetuating a vicious cycle that eventually leads to a more severe hypertensive phenotype. Finally, neither the pathophysiological mechanisms mediating aldosterone-driven blood pressure rise, nor those mediating aldosterone-driven end-organ damage, are specifically blocked by standard first-line anti-hypertensive drugs, which might further account for the drug-resistant phenotype that frequently characterizes PA patients.     

Focused Design of Novel Cyclic Peptides Endowed with GABARAP-Inhibiting Activity

(1) Background: Disfunctions in autophagy machinery have been identified in various conditions, including neurodegenerative diseases, cancer, and inflammation. Among mammalian autophagy proteins, the Atg8 family member GABARAP has been shown to be greatly involved in the autophagy process of prostate cancer cells, supporting the idea that GABARAP inhibitors could be valuable tools to fight the progression of tumors. (2) Methods: In this paper, starting from the X-ray crystal structure of GABARAP in a complex with an AnkirinB-LIR domain, we identify two new peptides by applying in silico drug design techniques. The two ligands are synthesized, biophysically assayed, and biologically evaluated to ascertain their potential anticancer profile. (3) Results: Two cyclic peptides (WC8 and WC10) displayed promising biological activity, high conformational stability (due to the presence of disulfide bridges), and K_d values in the low micromolar range. The anticancer assays, performed on PC-3 cells, proved that both peptides exhibit antiproliferative effects comparable to those of peptide K1, a known GABARAP inhibitor. (4) Conclusions: WC8 and WC10 can be considered new GABARAP inhibitors to be employed as pharmacological tools or even templates for the rational design of new small molecules.     

Chalcogenide Thermoelectrics Empowered by an Unconventional Bonding Mechanism

Thermoelectric materials have attracted significant research interest in recent decades due to their promising application potential in interconverting heat and electricity. Unfortunately, the strong coupling between the material parameters that determine thermoelectric efficiency, i.e., the Seebeck coefficient, electrical conductivity, and thermal conductivity, complicates the optimization of thermoelectric energy converters. Main‐group chalcogenides provide a rich playground to alleviate the interdependence of these parameters. Interestingly, only a subgroup of octahedrally coordinated chalcogenides possesses good thermoelectric properties. This subgroup is also characterized by other outstanding characteristics suggestive of an exceptional bonding mechanism, which has been coined metavalent bonding. This conclusion is further supported by a map that separates different bonding mechanisms. In this map, all octahedrally coordinated chalcogenides with good performance as thermoelectrics are located in a well‐defined region, implying that the map can be utilized to identify novel thermoelectrics. To unravel the correlation between chemical bonding mechanism and good thermoelectric properties, the consequences of this unusual bonding mechanism on the band structure are analyzed. It is shown that features such as band degeneracy and band anisotropy are typical for this bonding mechanism, as is the low lattice thermal conductivity. This fundamental understanding, in turn, guides the rational materials design for improved thermoelectric performance by tailoring the chemical bonding mechanism.     

Evidence for the Band‐Edge Exciton of CuInS2 Nanocrystals Enables Record Efficient Large‐Area Luminescent Solar Concentrators

Ternary I‐III‐VI₂ nanocrystals (NCs), such as CuInS₂, are receiving attention as heavy‐metals‐free materials for solar cells, luminescent solar concentrators (LSCs), LEDs, and bio‐imaging. The origin of the optical properties of CuInS₂ NCs are however not fully understood. A recent theoretical model suggests that their characteristic Stokes‐shifted and long‐lived luminescence arises from the structure of the valence band (VB) and predicts distinctive optical behaviours in defect‐free NCs: the quadratic dependence of the radiative decay rate and the Stokes shift on the NC radius. If confirmed, this would have crucial implications for LSCs as the solar spectral coverage ensured by low‐bandgap NCs would be accompanied by increased re‐absorption losses. Here, by studying stoichiometric CuInS₂ NCs, it is revealed for the first time the spectroscopic signatures predicted for the free band‐edge exciton, thus supporting the VB‐structure model. At very low temperatures, the NCs also show dark‐state emission likely originating from enhanced electron‐hole spin interaction. The impact of the observed optical behaviours on LSCs is evaluated by Monte Carlo ray‐tracing simulations. Based on the emerging device design guidelines, optical‐grade large‐area (30×30 cm²) LSCs with optical power efficiency (OPE) as high as 6.8% are fabricated, corresponding to the highest value reported to date for large‐area devices.