Manufacturing-as-a-Service (MaaS): state-of-the-art of up and running solutions and a framework to assess the level of development of a Cloud Manufacturing platform

During the last decades manufacturers tried to find new sources of flexibility because of the uncertainty of the market. Both practitioners and academics started to study new paradigms aiming to make companies more flexible up and downstream of their value chains leveraging on suppliers and customers. Cloud Manufacturing (CM) is certainly one of the most interesting concepts because it comes from the success of Cloud Computing and belongs to the complex fourth industrial revolution (i.e. Industry 4.0 paradigm). It has been introduced in 2010, defined as the “manufacturing version of cloud computing” where manufacturing resources are available to users on-demand, with outstanding flexibility. CM pursues the idea of creating Manufacturing as-a-Service (MaaS) leveraging on the benefits of the platform economy. In spite of its interest, after ten years debate there is not consensus on the essential characteristics of this paradigm because of the very limited number of real applications (prototypes excluded). In this paper we explore 6 cases of up and running platforms which resemble some of the characteristics of CM, define them as “CM Early adopters” and inductively propose a framework to assess the level of development of a CM platform. This study contributes to theory as it shows that CM is already arising in some businesses, the approach to the paradigm can vary significantly from one case to another, and different levels of development can be assessed. From a managerial point of view, this paper helps to understand the CM paradigm as it shows concrete examples of real companies pursuing the MaaS idea. In conclusion, MaaS seems ready to land on some industrial sectors and this can be either a new opportunity for competitiveness or a serious threat

Rapid and sensitive detection of bla KPC gene in clinical isolates of Klebsiella pneumoniae by a molecular real-time assay.

The aim of this study was the rapid identification of bla KPC gene in 38 Klebsiella pneumoniae clinical isolates with reduced susceptibility to carbapenems. The modified Hodge Test (MHT) was carried out to phenotypically determine whether resistance to carbapenems was mediated by a carbapenemase. The detection of the bla KPC gene was performed by real-time acid nucleic sequence-based amplification (NASBA™™), specifically designed for the detection of KPC RNA target.Thirty-two/38 isolates evaluated by MHT showed the production of carbapenemases, while all the strains exhibited the production of KPC by inhibition test with phenylboronic acid (the combined disk test with IPM/IPM plus phenylboronic acid). The detection of bla KPC gene by Nuclisens EasyQ KPC yielded positive results in 38/38 (100\%) strains. The presence of bla KPC gene was confirmed in all K. pneumoniae isolates when tested by the gold standard PCR assay.In consideration of the serious challenge represented by infections due to K. pneumoniae it appears necessary the rapid identification of carbapenemases in clinical settings as it is made possible by the use of NASBA™ assay

Equine CTNNB1 and PECAM1 nucleotide structure and expression analyses in an experimental model of normal and pathological wound repair

<p>Abstract</p> <p>Background</p> <p>Wound healing in horses is fraught with complications. Specifically, wounds on horse limbs often develop exuberant granulation tissue which behaves clinically like a benign tumor and resembles the human keloid in that the evolving scar is trapped in the proliferative phase of repair, leading to fibrosis. Clues gained from the study of over-scarring in horses should eventually lead to new insights into how to prevent unwanted scar formation in humans. cDNA fragments corresponding to <it>CTNNB1 </it>(coding for β-catenin) and <it>PECAM1</it>, genes potentially contributing to the proliferative phase of repair, were previously identified in a mRNA expression study as being up-regulated in 7 day wound biopsies from horses. The aim of the present study was to clone full-length equine <it>CTNNB1 </it>and <it>PECAM1 </it>cDNAs and to study the spatio-temporal expression of mRNAs and corresponding proteins during repair of body and limb wounds in a horse model.</p> <p>Results</p> <p>The temporal pattern of the two genes was similar; except for <it>CTNNB1 </it>in limb wounds, wounding caused up-regulation of mRNA which did not return to baseline by the end of the study. Relative over-expression of both <it>CTNNB1 </it>and <it>PECAM1 </it>mRNA was noted in body wounds compared to limb wounds. Immunostaining for both β-catenin and PECAM1 was principally observed in endothelial cells and fibroblasts and was especially pronounced in wounds having developed exuberant granulation tissue.</p> <p>Conclusion</p> <p>This study is the first to characterize equine cDNA for <it>CTNNB1 </it>and <it>PECAM1 </it>and to document that these genes are expressed during wound repair in horses. It appears that β-catenin may be regulated in a post-transcriptional manner while PECAM1 might help thoracic wounds mount an efficient inflammatory response in contrast to what is observed in limb wounds. Furthermore, data from this study suggest that β-catenin and PECAM1 might interact to modulate endothelial cell and fibroblast proliferation during wound repair in the horse.</p

Selection of Histological Parameters for the Development of an Analytical Method for Discriminating Fresh and Frozen/Thawed Common Octopus (Octopus vulgaris) and Preventing Frauds along the Seafood Chain

This study aimed at selecting effective histological indicators of the freezing process, for the discrimination of fresh and frozen common octopus Octopus vulgaris. Histological indices of freezing process were selected in mantle and arm muscle and axial nerve tissues. Seven histological parameters were chosen: overall muscle tissue structural organization (a); gaping among muscle bundles (b); presence of optically empty spaces between and within muscle bundles (c); white spaces percentage between and within muscle bundles (d); overall nerve structural organization (e); presence of linear fissures and/or empty spaces within neuropil and axonal tract (f); presence of empty spaces within connective tissue matrix surrounding the nerve (g); empty space percentage within arm axial nerve region (h). The parameters were assessed on 150 mantle muscle sections (a, b, c, d), 150 arm muscle (b, c) and nervous (e, f, g, h) tissue sections belonging to 20 fresh exemplars further subdued to conventional freezing procedure at − 20&nbsp;°C, 25 fresh curled exemplars, 25 exemplars industrially frozen at − 80&nbsp;°C, and 20 thawed, curled, and individually quick frozen exemplars. Overall structural organization (a, e), gaping (b), and presence of optically empty spaces (c, f) confirmed significant morphological freezing indices in mantle and arm sections. In mantle, two d values (d &lt; 25% and 25% &lt; d &lt; 33%) were proposed as complementary thresholds to be applied in association with b and c indices for freezing discrimination. These parameters appear eligible to set a method for discriminating fresh/thawed octopus products to be applied both in official control and self-check activities

Sopravvivenza di microrganismi potenzialmente patogeni su superfici porcellanate

È stata valutata la capacità di sopravvivere sulla superficie inerte porcellanata di tazzine da caffè di quattro microrganismi potenzialmente patogeni (Streptococcus pyogenes, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli). Dopo inoculazione è stata dimostrata capacità di sopravvivenza fino a 24 ore di Streptococcus pyogenes, Staphylococcus aureus ma non di Pseudomonas aeruginosa, Escherichia coli. Questi dati suggeriscono il potenziale ruolo patogeno giocato dalle superfici di stoviglie di largo uso nella trasmissione di infezioni da alcuni microrganismi gram-positivi

Sperm quality assessment in Ficopomatus enigmaticus (Fauvel, 1923): Effects of selected organic and inorganic chemicals across salinity levels

Contamination by organic and inorganic compounds remains one of the most complex problems in both brackish and marine environments, causing potential implications for the reproductive success and survival of several broadcast spawners. Ficopomatus enigmaticus is a tubeworm polychaete that has previously been used as a model organism for ecotoxicological analysis, due to its sensitivity and ecological relevance. In the present study, the effects of five trace elements (zinc, copper, cadmium, arsenic and lead), one surfactant (sodium dodecyl sulfate, SDS) and one polycyclic aromatic hydrocarbon (benzo(a)pyrene, B(a)P) on the sperm quality of F. enigmaticus were investigated. Sperm suspensions were exposed in vitro to different concentrations of each selected contaminant under four salinity conditions (10, 20, 30, 35). Possible adverse effects on sperm function were assessed by measuring oxidative stress, membrane integrity, viability and DNA damage. Sperm quality impairments induced by organic contaminants were more evident than those induced by inorganic compounds. SDS exerted the largest effect on sperm. In addition, F. enigmaticus sperm showed high tolerance to salinity variation, supporting the wide use of this species as a promising model organism for ecotoxicological assays. Easy and rapid methods on polychaete spermatozoids were shown to be effective as integrated sperm quality parameters or as an alternative analysis for early assessment of marine and brackish water pollution

The FHP01 DDX3X helicase inhibitor exerts potent anti-tumor activity in vivo in breast cancer pre-clinical models

Inhibition of DDX3X expression or activity reduces proliferation in cells from various tumor tissues, in particular in breast cancer, and its expression often correlates to tumor aggressiveness. This makes DDX3X a prominent candidate for the design of drugs for novel personalized therapeutic strategies. Starting from an in silico drug discovery approach, a group of molecules has been selected by molecular docking at the RNA binding site of DDX3X. Here, the most promising among them, FHP01, was evaluated in breast cancer preclinical models. Specifically, FHP01 exhibited very effective antiproliferative and killing activity against different breast cancer cell types, among which those from triple-negative breast cancer (TNBC). Interestingly, FHP01 also inhibited WNT signaling, a key tumorigenic pathway already correlated to DDX3X functions in breast cancer model cell lines. Ultimately, FHP01 also caused a significant reduction, in vivo, in the growth of MDA MB 231- derived TNBC xenograft models. Importantly, FHP01 showed good bioavailability and no toxicity on normal peripheral blood mononuclear cells in vitro and on several mouse tissues in vivo. Overall, our data suggest that the use of FHP01 and its related compounds may represent a novel therapeutic approach with high potential against breast cancer, including the triple-negative subtype usually correlated to the most unfavorable outcomes because of the lack of available targeted therapies

The path from trigeminal asymmetry to cognitive impairment: a behavioral and molecular study

Trigeminal input exerts acute and chronic effects on the brain, modulating cognitive functions. Here, new data from humans and animals suggest that these effects are caused by trigeminal influences on the Locus Coeruleus (LC). In humans subjects clenching with masseter asymmetric activity, occlusal correction improved cognition, alongside with reductions in pupil size and anisocoria, proxies of LC activity and asymmetry, respectively. Notably, reductions in pupil size at rest on the hypertonic side predicted cognitive improvements. In adult rats, a distal unilateral section of the trigeminal mandibular branch reduced, on the contralateral side, the expression of c-Fos (brainstem) and BDNF (brainstem, hippocampus, frontal cortex). This counterintuitive finding can be explained by the following model: teeth contact perception loss on the lesioned side results in an increased occlusal effort, which enhances afferent inputs from muscle spindles and posterior periodontal receptors, spared by the distal lesion. Such effort leads to a reduced engagement of the intact side, with a corresponding reduction in the afferent inputs to the LC and in c-Fos and BDNF gene expression. In conclusion, acute effects of malocclusion on performance seem mediated by the LC, which could also contribute to the chronic trophic dysfunction induced by loss of trigeminal input

High-Dose, Extended-Interval Colistin Administration in Critically Ill Patients: Is This the Right Dosing Strategy? A Preliminary Study

In critically ill patients with otherwise untreatable nosocomial infection due to gram-negative bacteria susceptible only to colistin, a high-dose, extended-interval colistin dosing regimen is, according to the pharmacokinetic/pharmacodynamic behavior of the drug, associated with low renal toxicity and high efficacy