Polysorbate identity and quantity dictate the extensional flow properties of protein-excipient solutions

While protein medications are promising for treatment of cancer and autoimmune diseases, challenges persist in terms of development and injection stability of high-concentration formulations. Here, the extensional flow properties of protein-excipient solutions are examined via dripping-onto-substrate extensional rheology, using a model ovalbumin (OVA) protein and biocompatible excipients polysorbate 20 (PS20) and 80 (PS80). Despite similar PS structures, differences in extensional flow are observed based on PS identity in two regimes: at moderate total concentrations where surface tension differences drive changes in extensional flow behavior, and at small PS:OVA ratios, which impact the onset of weakly elastic flow behavior. Undesirable elasticity is observed in ultra-concentrated formulations, independent of PS identity; higher PS contents are required to observe these effects than in analogous polymeric excipient solutions. These studies reveal novel extensional flow behaviors in protein-excipient solutions, and provide a straightforward methodology for assessing the extensional flow stability of new protein-excipient formulations.     

Effect of Bonder at Skin/Core Interface on the Mechanical Performances of Sandwich Structures Used in Marine Industry

The present work is aimed to extend the knowledge of mechanical properties of sandwich structures used for marine applications focusing on the possibility to increase the performances of such structures by adding a bonder at the skin/core interface. Therefore, three sandwich structures that are utilised in different structural components of a yacht were realised by manual lay-up. The mechanical characterisation was performed by flatwise compressive, edgewise compressive and three point flexural tests. The tests execution has allowed both to determine the mechanical performances and to understand the fracture mechanisms that take place when the bonder is added in the stacking sequence of the samples.     

Degradation of lincomycin in aqueous medium: Coupling of solar photocatalysis and membrane separation

The photocatalytic oxidation of a common antibiotic, the lincomycin was carried out in aqueous suspensions of polycrystalline TiO₂ Degussa P25 irradiated by sunlight. In order to improve the performance of the lincomycin degradation a hybrid system consisting of a solar photoreactor with the photocatalyst in suspension coupled with a membrane module, used to confine both photocatalyst and pollutants in the reaction environment, was tested.A preliminary study was carried out in order to determine some kinetics parameters of the drug photodegradation. The influence of initial substrate concentration on the lincomycin photooxidation rate was investigated. The photooxidation rate follows a pseudo-first order kinetics with respect to the lincomycin concentration under the used experimental conditions. The presence of the membrane reactor allows the catalyst separation and to operate in continuous mode as the membranes rejection for lincomycin and its oxidation products was quite high.     

Shifting physician prescribing to a preferred histamine-2-receptor antagonist. Effects of a multifactorial intervention in a mixed-model health maintenance organization

Three receptor tyrosine kinases of the PDGF receptor family (RTKP) that clustered within 1000 Kb of the mouse chromosome 5 constitute an interesting unit that are expressed in three distinct cell lineages essential for constructing hematopoietic tissues. Namely, the c-kit gene that is expressed in hematopoietic stem cells is flanked by pdgfr alpha and flk genes expressed respectively in stromal cells and vascular endothelial cells. In this article, we review our results on their expression in the embryonic hematopoietic tissues. We found that co-expression of Flkl and c-Kit was frequently detected either in vascular endothelial cells or hematopoietic cells in the early hematopoietic tissues. On the other hand, the three RTKPs are expressed in different cell lineages in the fetal liver. On the basis of this finding, we propose two modes of embryonic hematopoiesis; hematogenic angiopoiesis and hematopoiesis.     

BRAF Gene and Melanoma: Back to the Future

As widely acknowledged, 40–50% of all melanoma patients harbour an activating BRAF mutation (mostly BRAF V600E). The identification of the RAS–RAF–MEK–ERK (MAP kinase) signalling pathway and its targeting has represented a valuable milestone for the advanced and, more recently, for the completely resected stage III and IV melanoma therapy management. However, despite progress in BRAF-mutant melanoma treatment, the two different approaches approved so far for metastatic disease, immunotherapy and BRAF+MEK inhibitors, allow a 5-year survival of no more than 60%, and most patients relapse during treatment due to acquired mechanisms of resistance. Deep insight into BRAF gene biology is fundamental to describe the acquired resistance mechanisms (primary and secondary) and to understand the molecular pathways that are now being investigated in preclinical and clinical studies with the aim of improving outcomes in BRAF-mutant patients.     

Manufacturing of polypropylene laminates and related structural reorganization in the crystalline phase

The conditions for obtaining recrystallization in more ordered modifications are described for an uniaxially oriented sample of isotactic polypropylene, annealed with fixed ends. These recrystallization conditions are related to the conditions of a lamination process.     

Privacy leakage on the Web: Diffusion and countermeasures

Protecting privacy on the Web is becoming increasingly complicated because of the considerable amount of personal and sensitive information left by users in many locations during their Web browsing and the silent actions of third party sites that collect data, aggregate information and build personal profiles of Internet users in order to provide free and personalized services. On the other hand, most of people are unaware that their information may be collected online, and that, after their aggregation from multiple sources, could be used for secondary purposes, such as linked to allow identification, without user’s notice.     

An optimization framework for “build-or-buy” decisions in software architecture

Building a software architecture that meets functional requirements is a quite consolidated activity, whereas keeping high quality attributes is still an open challenge. In this paper we introduce an optimization framework that supports the decision whether to buy software components or to build them in-house upon designing a software architecture. We devise a non-linear cost/quality optimization model based on decision variables indicating the set of architectural components to buy and to build in order to minimize the software cost while keeping satisfactory values of quality attributes. From this point of view, our tool can be ideally embedded into a Cost Benefit Analysis Method to provide decision support to software architects. The novelty of our approach consists in building costs and quality attributes on a common set of decision variables related to software development. We start from a special case of the framework where the quality constraints are related to the delivery time and the product reliability, and the model solution also devises the amount of unit testing to be performed on built components. We generalize the framework formulation to represent a broader class of architectural cost-minimization problems under quality constraints, and discuss advantages and limitations of such approach.     

Degree-Optimal Routing for P2P Systems

We define a family of Distributed Hash Table systems whose aim is to combine the routing efficiency of randomized networks—e.g. optimal average path length O(log ² n/δlog δ) with δ degree—with the programmability and startup efficiency of a uniform overlay—that is, a deterministic system in which the overlay network is transitive and greedy routing is optimal. It is known that Ω(log n) is a lower bound on the average path length for uniform overlays with O(log n) degree (Xu et al., IEEE J. Sel. Areas Commun. 22(1), 151–163, 2004). Our work is inspired by neighbor-of-neighbor (NoN) routing, a recently introduced variation of greedy routing that allows us to achieve optimal average path length in randomized networks. The advantage of our proposal is that of allowing the NoN technique to be implemented without adding any overhead to the corresponding deterministic network. We propose a family of networks parameterized with a positive integer c which measures the amount of randomness that is used. By varying the value c, the system goes from the deterministic case (c=1) to an “almost uniform” system. Increasing c to relatively low values allows for routing with asymptotically optimal average path length while retaining most of the advantages of a uniform system, such as easy programmability and quick bootstrap of the nodes entering the system. We also provide a matching lower bound for the average path length of the routing schemes for any c. This work was partially supported by the Italian FIRB project “WEB-MINDS” (Wide-scalE, Broadband MIddleware for Network Distributed Services), .