Supply chain network design for the diffusion of a new product

Supply Chain Network Design (SCND) deals with the determination of the physical configuration and infrastructures of the supply chain. Specifically, facility location is one of the most critical decisions: transportation, inventory and information sharing decisions can be readily re-optimized in response to changes in the context, while facility location is often fixed and difficult to change even in the medium term. On top of this, when designing a supply network to support a new product diffusion (NPD), the problem becomes both dynamic and stochastic. While literature concentrated on approaching SCND for NPD separately coping with dynamic and stochastic issues, we propose an integrated optimisation model, which allows warehouse positioning decisions in concert with the demand dynamics during the diffusion stage of an innovative product/service. A stochastic dynamic model, which integrates a Stochastic Bass Model (SBM) in order to better describe and capture demand dynamics, is presented. A myopic policy is elaborated in order to solve and validate on the data of a real case of SCND with 1,400 potential market points and 28 alternatives for logistics platforms

Biomechanical and electromyographic assessment of spastic hypertonus in motor complete traumatic spinal cord-injured individuals

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First proof-of-principle of inorganic lead halide perovskites deposition by magnetron-sputtering

The present work reports the application of RF-magnetron sputtering technique to realize CsPbBr 3 70 nm thick films on glass substrate by means of a one-step procedure. The obtained films show highly uniform surface morphology and homogeneous thickness as evidenced by AFM and SEM investigations. XRD measurements demonstrate the presence of two phases: a dominant orthorhombic CsPbBr 3 and a subordinate CsPb 2 Br 5 . Finally, XPS data reveals surface bromine depletion respect to the stoichiometrical CsPbBr 3 composition, nevertheless photoluminescence spectroscopy results confirm the formation of a highly luminescent film. These preliminary results demonstrate that our approach could be of great relevance for easy fabrication of large area perovskite thin films. Future developments, based on this approach, may include the realization of multijunction solar cells and multicolor light emitting devices

CA-IX-Expressing Small Extracellular Vesicles (sEVs) Are Released by Melanoma Cells under Hypoxia and in the Blood of Advanced Melanoma Patients

Cutaneous melanoma is a highly aggressive skin cancer, with poor prognosis. The tumor microenvironment is characterized by areas of hypoxia. Carbonic anhydrase IX (CA-IX) is a marker of tumor hypoxia and its expression is regulated by hypoxia-inducible factor-1 (HIF-1). CA-IX has been found to be highly expressed in invasive melanomas. In this study, we investigated the effects of hypoxia on the release of small extracellular vesicles (sEVs) in two melanoma in vitro models. We demonstrated that melanoma cells release sEVs under both normoxic and hypoxic conditions, but only hypoxia-induced sEVs express CA-IX mRNA and protein. Moreover, we optimized an ELISA assay to provide evidence for CA-IX protein expression on the membranes of the sEVs. These CA-IX-positive sEVs may be exploited as potential biomarkers for liquid biopsy

Hedgehog Pathway Inhibition by Novel Small Molecules Impairs Melanoma Cell Migration and Invasion under Hypoxia

Melanoma is the principal cause of death in skin cancer due to its ability to invade and cause metastasis. Hypoxia, which characterises the tumour microenvironment (TME), plays an important role in melanoma development, as cancer cells can adapt and acquire a more aggressive phenotype. Carbonic anhydrases (CA) activity, involved in pH regulation, is related to melanoma cell migration and invasion. Furthermore, the Hedgehog (Hh) pathway, already known for its role in physiological processes, is a pivotal character in cancer cell growth and can represent a promising pharmacological target. In this study, we targeted Hh pathway components with cyclopamine, glabrescione B and C22 in order to observe their effect on carbonic anhydrase XII (CAXII) expression especially under hypoxia. We then performed a migration and invasion assay on two melanoma cell lines (SK-MEL-28 and A375) where Smoothened, the upstream protein involved in Hh regulation, and GLI1, the main transcription factor that determines Hh pathway activation, were chemically inhibited. Data suggest the existence of a relationship between CAXII, hypoxia and the Hedgehog pathway demonstrating that the chemical inhibition of the Hh pathway and CAXII reduction resulted in melanoma migration and invasion impairment especially under hypoxia. As in recent years drug resistance to small molecules has arisen, the development of new chemical compounds is crucial. The multitarget Hh inhibitor C22 proved to be effective without signs of cytotoxicity and, for this reason, it can represent a promising compound for future studies, with the aim to reach a better melanoma disease management

Polarized Raman mapping and phase-transition by CW excitation for fast purely optical characterization of VO2 thin films

Vanadium dioxide has attracted much interest due to the drastic change of the electrical and optical properties it exhibits during the transition from the semiconductor state to the metallic state, which takes place at a critical temperature of about 68 °C. Much study has been especially devoted to developing advanced fabrication methodologies to improve the performance of VO2 thin films for phase-change applications in optical devices. Films structural and morphological characterisation is normally performed with expensive and time consuming equipment, as x-ray diffractometers, electron microscopes and atomic force microscopes. Here we propose a purely optical approach which combines Polarized Raman Mapping and Phase-Transition by Continuous Wave Optical Excitation (PTCWE) to acquire through two simple measurements structural, morphological and thermal behaviour information on polycrystalline VO2 thin films. The combination of the two techniques allows to reconstruct a complete picture of the properties of the films in a fast and effective manner, and also to unveil an interesting stepped appearance of the hysteresis cycles probably induced by the progressive stabilization of rutile metallic domains embedded in the semiconducting monoclinic matrix

Comparison between Ischemic and Hemorrhagic Strokes in Functional Outcome at Discharge from an Intensive Rehabilitation Hospital

Comparison studies on recovery outcomes in ischemic (IS) and hemorrhagic strokes (HS) have yielded mixed results. In this retrospective observational study of consecutive IS and HS patients, we aimed at evaluating functional outcomes at discharge from an intensive rehabilitation hospital, comparing IS vs. HS, analyzing possible predictors. Modified Rankin Scale (mRS) at discharge was the main outcome. Out of the 229 patients included (mean age 72.9 ± 13.9 years, 48% males), 81 had HS (35%). Compared with IS (n = 148), HS patients were significantly younger (75 ± 12.5 vs. 68.8 ± 15.4 years, p = 0.002), required longer hospitalizations both in acute (23.9 ± 36.7 vs. 35.2 ± 29.9 days, p = 0.019) and rehabilitation hospitals (41.5 ± 31.8 vs. 77.2 ± 51.6 days, p = 0.001), and had more severe initial clinical deficit (mean number of neurological impairments: 2.0 ± 1.1 vs. 2.6 ± 1.4, p = 0.001) and mRS scores at admission (p = 0.046). At discharge, functional status change, expressed as mRS, was not significantly different between IS and HS (F = 0.01, p = 0.902), nor was the discharge destination (p = 0.428). Age and clinical severity were predictors of functional outcome in both stroke types. On admission in an intensive rehabilitation hospital, HS patients presented a worse functional and clinical status compared to IS. Despite this initial gap, the two stroke types showed an overlapped trajectory of functional recovery, with age and initial stroke severity as the main prognostic factors

Mutation profile of BBS genes in patients with Bardet-Biedl syndrome : An Italian study

Background: Bardet-Biedl syndrome (BBS) is a rare inherited multisystemic disorder with autosomal recessive or complex digenic triallelic inheritance. There is currently no treatment for BBS, but some morbidities can be managed. Accurate molecular diagnosis is often crucial for the definition of appropriate patient management and for the development of a potential personalized therapy. Methods: We developed a next-generation-sequencing (NGS) protocol for the screening of the 18 most frequently mutated genes to define the genotype and clarify the mutation spectrum of a cohort of 20 BBS Italian patients. Results: We defined the causative variants in 60% of patients; four of those are novel. 33% of patients also harboured variants in additional gene/s, suggesting possible oligogenic inheritance. To explore the function of different genes, we looked for correlations between genotype and phenotype in our cohort. Hypogonadism was more frequently detected in patients with variants in BBSome proteins, while renal abnormalities in patients with variations in BBSome chaperonin genes. Conclusions: NGS is a powerful tool that can help understanding BBS patients' phenotype through the identification of mutations that could explain differences in phenotype severity and could provide insights for the development of targeted therapy. Furthermore, our results support the existence of additional BBS loci yet to be identified

In vitro cell culture of amniotic fluid keratinocytes on amniotic membrane: the ideal tissue for repairing skin ulcers

OBJECTIVE: The amniotic fluid contains a large population of stem keratinocytes demonstrating minimal immunological rejection. Recent evidence suggests that stem cells from the amniotic fluid can be employed in the field of tissue engineering. In this work we identified precursors of the epithelial cells and expanded them in vitro.MATERIALS AND METHODS: After collecting samples of amniotic fluid and separating the cells via centrifugation, we seeded a portion of these cells in selection media to analyze the proliferation of epithelial cells. The stem cells precursors of keratinocytes were identified through specific markers. The expression of these markers was evaluated by immunofluorescence and reverse transcription polymerase chain reaction (PCR).RESULTS: The stem cells demonstrated 90% confluence, after undergoing proliferation in the selection medium for 15 days. Most of these cells tested positive for the keratinocyte-specific markers, but negative for stem cell specific markers. Of note, the identity of the keratinocytes was well established even after several subcultures.CONCLUSIONS: These results suggested that it is feasible to isolate and expand differentiated cell populations in the amniotic fluid from precursor cells. Furthermore, amniotic membranes can be utilized as scaffolds to grow keratinocytes, which can be potentially exploited in areas of skin ulcer transplantation and tissue engineering interventions