Anti-tumor activity of functionalized biomimetic magnetite nanoparticles produced in the presence of MamC protein of Magnetococcus marinus MC-1

Magnetite Nanoparticles (MNPs) find many applications, including biotechnology, as they can be manipulated by an external magnetic field and functionalized with different molecules. Magnetotactic bacteria bio-mineralize magnetosomes (membrane-enveloped magnetites), which are the ideal magnetic particle. However, scaling-up magnetosome production is still challenging, so bio-mimetics, i.e. in vitro magnetite synthesis mediated by magnetosome-associated proteins is being explored. Our group is working with MamC from Magnetococcus marinus MC-1 that controls the morphology and size of the crystals, producing well faceted Biomimetic Magnetic Nanoparticles (BMNPs) of ~40 nm, which are paramagnetic at room and body temperature while having a large magnetic moment per particle under an external magnetic field. These BMNPs were cytocompatible and biocompatible in vivo. BMNPs were functionalized (isothermal adsorption) with a monoclonal antibody (mAb) recognizing the ectodomain of the human Met/HGF receptor (overexpressed in many cancers) and the chemotherapeutic Doxorubicin (DOXO). The functionalized BMNPs present hyperthermia and were stable at physiological pH, while releasing the adsorbed DOXO at acidic pH. mAb functionalization of BMNPs favored their interaction with cells expressing the Met/HGFR and cellular DOXO uptake and toxicity, which was enhanced upon cell exposition to a continuous magnetic field. Real-time cytotoxicity of the BMNPs showed that DOXO-mAb-BMNPs were significantly more toxic than DOXO-BMNPs on Met/HGFR expressing cells, while no differential toxicity was observed on cells not expressing this receptor. When DOXO-BMNPs were injected intravenously in tumor bearing mice and an external magnetic field was applied there, a higher amount of BMNPs accumulated in the tumor and tumor growth was decreased in comparison to mice in which no magnetic field was applied. These BMNPs could thus represent effective nano-carriers for targeted drug delivery and might be combined with hyperthermia to increase efficiency, resulting in a targeted local treatment of tumors with a decrease in the deleterious systemic side effects

Improving software process accountability with Spago4Q

Accountability in current development processes is achieved following invasive procedures that oblige developers to strictly follow organizations\u2019 policies, making such an important aspect for development process an onerous task. In this paper, we present the open source application Spago4Q, a flexible process monitoring tool designed for maturity assessment but adaptable for tasks like accountability monitoring

Improving quality and cost-effectiveness in enterprise software application development : an open holistic approach for project monitoring and control

The availability of integrated software tools can help organizations to easily and quickly achieve higher maturity and capability levels in process improvement and change management initiatives, by effectively supporting easy data and information sharing. However, despite their usefulness, their implementation costs still often represent a not trivial constraint for their adoption. In order to overcome such constraints, Open Source Software (OSS) can represent the right solution. Among the plenty of OSS freely available on the Net, only a very reduced set deals with measurement and monitoring & control processes, which instead represent two core processes in well-known SPI models. This paper proposes a case study showing how to efficiently detect possible project improvements using a combination of software engineering measurement-related techniques supported by the OS platform Spago4Q, keeping the focus on the need of organizations to strengthen its historical data gathering process

Osteonecrosis of the jaws in patients treated with bisphosphonates. Review of the literature and the Milan experience

AIM: A series of 5 patients with osteonecrosis of the jaws possibly related to the use of bisphosphonates is presented. A brief review of the literature is also proposed. METHODS: A retrospective review of patients who received bisphophonates and who developed osteonecrosis of the jaws following minor oral surgery was performed. RESULTS: In all 5 patients, a tooth extraction preceded the onset of osteonecrosis of the mandible. Patients were on chronic use of intravenous bisphosphonates. The presenting lesions was a nonhealing extraction socket and an exposed jawbone. Biopsy of the bone lesions showed no evidence of metastatic involvement. Antibiotic therapy, conservative debridement and, in some cases, bone sequestrectomy were performed. CONCLUSIONS: Osteonecrosis of the jaws appears to have a relationship with the use of bisphosphonates. It is important that medical oncologists and dentists become aware of this possible complication in order to perform minor oral surgery prior to starting bisphosphonates treatment

Balanced measurement sets : criteria for improving project management practices

The availability of a measurement framework right at the early stage of a project can have a very positive impact in the management of software development process. In this paper, we cope with this problem proposing a methodology that can allow an early adoption of balanced measurement sets, which will be iteratively refined at each iteration of the process. The proposed methodology can be implemented and supported by open source tools like the Spago4Q platform

The use of a meta-model to support multi-project process measurement

In today's environment, software companies are engaged in multiple projects delivered on heterogeneous platforms for a wide class of applications in disparate application domains. They are increasingly engaged in the co-development of software systems through joint software development projects including stafffrom partners and customers as well as their own. As a result, they must support multiple software development processes while trying to guarantee uniform levels of process enactment, and product quality across all projects. Our approach is capable of providing process measurement in a joint-project, multi-process model business environment. It is based on a simple meta-model for computing across-process, multiple-project metrics designed to permit monitoring of CMMI compliance. The open source tool Spago4Q has been developed to support our approach and is capable of producing the measurements needed for monitoring of a set of large-scale development projects using different process models, in a real industrial setting in Europe. The results support the view that that it will not always be possible to aggregate the same set of metrics across disparate process models

Spago4Q and the QEST nD model : an open source solution for software performance measurement

Improving the software development process requires tools and model of increasing complexity, capable of satisfying project managers\u2019 and analyzers\u2019 needs. In that paper we present a solution integrating a formalized and established model for performance evaluation like QEST nD, and an open source Business Intelligence platform like Spago4Q. We obtain a new environment that can produce immediate snapshots of projects\u2019 status without any constraint on the number of projects and the type of development process

Induced nucleation of biomimetic nanoapatites on exfoliated graphene biomolecule flakes by vapor diffusion in microdroplets

The nucleation of apatite nanoparticles on exfoliated graphene nanoflakes has been successfully carried out by the sitting drop vapor diffusion method, with the aim of producing cytocompatible hybrid nanocomposites of both components. The graphene flakes were prepared by the sonication-assisted, liquid-phase exfoliation technique, using the following biomolecules as dispersing surfactants: lysozyme, L-tryptophan, N-acetyl-D-glucosamine, and chitosan. Results from mineralogical, spectroscopic, and microscopic characterization (X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Raman, Variable pressure scanning electron microscopy (VPSEM), and transmission electron microscopy (TEM)) indicate that flakes were stacked in multilayers (> 5 layers) and most likely intercalated and functionalized with the biomolecules, while the apatite nanoparticles were found forming a coating on the graphene surfaces. It is worthwhile to mention that when using chitosan-exfoliated graphene, the composites were more homogeneous than when using the other biomolecule graphene flakes, suggesting that this polysaccharide, extremely rich in \u2013OH groups, must be arranged on the graphene surface with the \u2013OH groups pointing toward the solution, forming a more regular pattern for apatite nucleation. The findings by XRD and morphological analysis point to the role of \u201cfunctionalized graphene\u201d as a template, which induces heterogeneous nucleation and favors the growth of apatite on the flakes\u2019 surfaces. The cytocompatibility tests of the resulting composites, evaluated by the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay in a dose\u2013 dependent manner on GTL-16 cells, a human gastric carcinoma cell line, and on m17.ASC cells, a murine mesenchymal stem cell line with osteogenic potential, reveal that in all cases, full cytocompatibility was found

Myogenic potential of extracellular matrix derived from decellularized bovine pericardium

Skeletal muscles represent 40% of body mass and its native regenerative capacity can be permanently lost after a traumatic injury, congenital diseases, or tumor ablation. The absence of physiological regeneration can hinder muscle repair preventing normal muscle tissue functions. To date, tissue engineering (TE) represents one promising option for treating muscle injuries and wasting. In particular, hydrogels derived from the decellularized extracellular matrix (dECM) are widely investigated in tissue engineering applications thanks to their essential role in guiding muscle regeneration. In this work, the myogenic potential of dECM substrate, obtained from decellularized bovine pericardium (Tissuegraft Srl), was evaluated in vitro using C2C12 murine muscle cells. To assess myotubes formation, the width, length, and fusion indexes were measured during the differentiation time course. Additionally, the ability of dECM to support myogenesis was assessed by measuring the expression of specific myogenic markers: α-smooth muscle actin (α-sma), myogenin, and myosin heavy chain (MHC). The results obtained suggest that the dECM niche was able to support and enhance the myogenic potential of C2C12 cells in comparison of those grown on a plastic standard surface. Thus, the use of extracellular matrix proteins, as biomaterial supports, could represent a promising therapeutic strategy for skeletal muscle tissue engineering