Transactional scheduling for read-dominated workloads

The transactional approach to contention management guarantees atomicity by aborting transactions that may violate consistency. A major challenge in this approach is to schedule transactions in a manner that reduces the total time to perform all transactions (the makespan), since transactions are often aborted and restarted. The performance of a transactional scheduler can be evaluated by the ratio between its makespan and the makespan of an optimal, clairvoyant scheduler that knows the list of resource accesses that will be performed by each transaction, as well as its release time and duration.     

Role of miRNA-19a in Cancer Diagnosis and Poor Prognosis

Cancer is a multifactorial disease that affects millions of people every year and is one of the most common causes of death in the world. The high mortality rate is very often linked to late diagnosis; in fact, nowadays there are a lack of efficient and specific markers for the early diagnosis and prognosis of cancer. In recent years, the discovery of new diagnostic markers, including microRNAs (miRNAs), has been an important turning point for cancer research. miRNAs are small, endogenous, non-coding RNAs that regulate gene expression. Compelling evidence has showed that many miRNAs are aberrantly expressed in human carcinomas and can act with either tumor-promoting or tumor-suppressing functions. miR-19a is one of the most investigated miRNAs, whose dysregulated expression is involved in different types of tumors and has been potentially associated with the prognosis of cancer patients. The aim of this review is to investigate the role of miR-19a in cancer, highlighting its involvement in cell proliferation, cell growth, cell death, tissue invasion and migration, as well as in angiogenesis. On these bases, miR-19a could prove to be truly useful as a potential diagnostic, prognostic, and therapeutic marker.     

Design,Synthesis, Biological Activity,and Structural Analysis of Lactam‐Constrained PTPRJ Agonist Peptides

PTPRJ is a receptor‐like protein tyrosine phosphatase mainly known for its antiproliferative and tumor‐suppressive functions. PTPRJ dephosphorylates several growth factors and their receptors, negatively regulating cell proliferation and migration. We recently identified a disulfide‐bridged nonapeptide, named PTPRJ‐19 (H‐[Cys‐His‐His‐Asn‐Leu‐Thr‐His‐Ala‐Cys]‐OH), which activates PTPRJ, thereby causing cell growth inhibition and apoptosis of both cancer and endothelial cells. With the aim of replacing the disulfide bridge by a chemically more stable moiety, we have synthesized and tested a series of lactam analogues of PTPRJ‐19 . This replacement led to analogues with higher activity and greater stability than the parent peptide.     

A New Human Platelet Lysate for Mesenchymal Stem Cell Production Compliant with Good Manufacturing Practice Conditions Preserves the Chemical Characteristics and Biological Activity of Lyo-Secretome Isolated by Ultrafiltration

Recently, we proposed a Good Manufacturing Practice (GMP)-compliant production process for freeze-dried mesenchymal stem cell (MSC)-secretome (lyo-secretome): after serum starvation, the cell supernatant was collected, and the secretome was concentrated by ultrafiltration and freeze-dried, obtaining a standardized ready-to-use and stable powder. In this work, we modified the type of human platelet lysate (HPL) used as an MSC culture supplement during the lyo-secretome production process: the aim was to verify whether this change had an impact on product quality and also whether this new procedure could be validated according to GMP, proving the process robustness. MSCs were cultured with two HPLs: the standard previously validated one (HPL-E) and the new one (HPL-S). From the same pool of platelets, two batches of HPL were obtained: HPL-E (by repeated freezing and thawing cycles) and HPL-S (by adding Ca-gluconate to form a clot and its subsequent mechanical wringing). Bone marrow MSCs from three donors were separately cultured with the two HPLs until the third passage and then employed to produce lyo-secretome. The following indicators were selected to evaluate the process performance: (i) the lyo-secretome quantitative composition (in lipids and proteins), (ii) the EVs size distribution, and (iii) anti-elastase and (iv) immunomodulant activity as potency tests. The new HPL supplementation for MSCs culture induced only a few minimal changes in protein/lipid content and EVs size distribution; despite this, it did not significantly influence biological activity. The donor intrinsic MSCs variability in secretome secretion instead strongly affected the quality of the finished product and could be mitigated by concentrating the final product to reach a determined protein (and lipid) concentration. In conclusion, the modification of the type of HPL in the MSCs culture during lyo-secretome production induces only minimal changes in the composition but not in the potency, and therefore, the new procedure can be validated according to GMP.     

Molecular Recognition of the HPLC Whelk-O1 Selector towards the Conformational Enantiomers of Nevirapine and Oxcarbazepine

The presence of stereogenic elements is a common feature in pharmaceutical compounds, and affording optically pure stereoisomers is a frequent issue in drug design. In this context, the study of the chiral molecular recognition mechanism fundamentally supports the understanding and optimization of chromatographic separations with chiral stationary phases. We investigated, with molecular docking, the interactions between the chiral HPLC selector Whelk-O1 and the stereoisomers of two bioactive compounds, the antiviral Nevirapine and the anticonvulsant Oxcarbazepine, both characterized by two stereolabile conformational enantiomers. The presence of fast-exchange enantiomers and the rate of the interconversion process were studied using low temperature enantioselective HPLC and VT-NMR with Whelk-O1 applied as chiral solvating agent. The values of the energetic barriers of interconversion indicate, for the single enantiomers of both compounds, half-lives sufficiently long enough to allow their separation only at critically sub-ambient temperatures. The chiral selector Whelk-O1 performed as a strongly selective discriminating agent both when applied as a chiral stationary phase (CSP) in HPLC and as CSA in NMR spectroscopy.     

Benchmark exercise on risk assessment methods applied to a virtual hydrogen refuelling station

A benchmarking exercise on quantitative risk assessment (QRA) methodologies for hydrogen safety has been conducted within the project HyQRA, under the framework of the European Network of Excellence (NoE), HySafe. The aim of the exercise was twofold: (i) to identify the differences and similarities in approaches in a QRA and their results for a hydrogen installation and (ii) to identify knowledge gaps in the various steps and parameters underlying the risk quantification of hydrogen safety.First, a reference case was defined for the benchmark: a virtual hydrogen refuelling station (HRS) in virtual surroundings comprising housing, school, shops and other vulnerable objects. For the study, a two phase approach was followed.In phase 1, all nine partners were requested to conduct a QRA according to their usual approach and experience. Basically, participants were free to define representative release cases, to apply models and frequency assessments according their own methodology, and to present risk according to their usual format. To enable inter-comparison, a required set of results data was prescribed, like distances to specific thermal radiation levels from fires and distances to specific overpressure levels. Moreover, complete documentation of assumptions, base data and references was to be reported.It was not surprising that a wide range of results was obtained, both in the applied approaches as well as in the quantitative outcomes and conclusions. This made it difficult to identify exactly which assumptions and parameters were responsible for the differences in results.These results provided the basis for a more guided QRA, the second phase. This phase 2 was defined in which the QRA was determined by a more limited number of release cases (scenarios). The partners in the project agreed to assess specific scenarios in order to identify the differences in consequence assessment approaches. The results of this phase provide a better understanding of the influence of modelling assumptions and limitations on the eventual conclusions with regard to risk to on-site people and to the off-site public.     

A framework to manage reconfigurability in manufacturing

Nowadays, manufacturing firms are dealing with the unpredictability of market requirements and the frequent changes induced by technological innovation. For this reason, firms are more and more addressing the need to be responsive at an affordable cost. To do so, they are required to develop a capability called reconfigurability. This paper is a review of the existing literature because the current need makes interesting to reflect on the state of the art of reconfigurability as a concept. This reflection has led to focus on reconfigurability characteristics for both their relevance and their relationships with managerial decisions in manufacturing. To this end, a framework has been proposed. It is based on system lifecycle and production levels. These two elements have been deduced from literature and identified as relevant dimensions for decision-making.     

A Ginzburg–Landau model for material aging depending on temperature

ABSTRACT

We consider a model describing the behavior of a body subject to aging and fatigue. These phenomena are supposed to be affected by both mechanical and thermal effects. The material is assumed to be viscoelastic where the stress–strain relation is based on a new fractional derivative proposed in Caputo and Fabrizio. The order of derivative is regarded as a new variable whose evolution is ruled by a Ginzburg–Landau equation. The model also includes an evolutive equation for the temperature deducing from the first law of thermodynamics. In this article, thermodynamic compatibility is shown and some numerical simulations are performed.