Expression, purification and in vitro biological activity from human recombinant BMP-2 produced by a novel approach

Bone morphogenetic proteins have promoted great biomedical interest due to their ability in inducing new bone formation when used as powerful osteoinductive components of several late-stage bone grafting products. Recombinant human bone morphogenetic protein-2 (rhBMP-2) is obtained from mammalian cell expressing systems in low amounts or from bacteria inclusion bodies after timeconsuming refolding methods. Thus, there is a need to establish novel approaches for producing rhBMP-2 in high yields by simple and cheap procedures.Portuguese Foundation for Science and Technolog y, FCT (PhD Grant to PC Bessa , SFRH/BD/17049/2004). This work was also partially supported by the European STREP HIPPOCRATES (NMP3 - CT - 2003 - 505758) and carried out under the scope of European NoE EXPERTISSUES (NMP3 - CT - 2004 - 500283).info:eu-repo/semantics/publishedVersio

A novel approach for the production of human recombinant BMP-2 for bone tissue engineering applications

Bone tissue engineering has been an increasing field of research during the last years. The ideal approach for a regenerative application would consist in the use of cells from the patient, scaffolding materials and differentiation growth factors. Bone morphogenetic protein-2 (BMP-2) is one such growth factors with a strong ability to induce new bone and cartilage formation and has been used as a powerful osteoinductive component of several late-stage tissue engineering products for bone grafting. In this work, we aimed at obtaining high yields of human recombinant BMP-2 in a stable, pure and biologically active form by use of a new bacteria expression system that circumvents the disadvantages of conventional recombinant protein preparation methods and to perform a study of the stability conditions and the functionality of these peptides in vitro in human mesenchymal stem cells and C2C12 murine cell line.info:eu-repo/semantics/publishedVersio

Expression, purification and in vitro biological activity from human recombinant BMP-2 produced by a novel approach

Bone tissue engineering has been an increasing field of research during the last years. The ideal approach for a regenerative application would consist in the use of cells from the patient, scaffolding materials and differentiation growth factors. Bone morphogenetic protein-2 (BMP-2) is one such growth factors with a strong ability to induce new bone and cartilage formation and has been used as a powerful osteoinductive component of several late-stage tissue engineering products for bone grafting. In this work, we aimed at obtaining high yields of human recombinant BMP-2 in a stable, pure and biologically active form by use of a new bacteria expression system that circumvents the disadvantages of conventional recombinant protein preparation methods and to perform a study of the stability conditions and functionality of these peptides in vitro in human mesenchymal stem cells and C2C12 murine cell line.Portuguese Foundation for Science and Technology, FCT (PhD Grant to PC Bessa, to PC Bessa, SFRH/BD/17049/2004 SFRH/BD/17049/2004 ). This work was ). This work was also partially supported by the European STREP HIPPOCRATES (NMP3 also partially supported by the European STREP HIPPOCRATES (NMP3--CTCT--2003 2003--505758) and carried out under the scope of 505758) and carried out under the scope of European NoE EXPERTISSUES (NMP3 European NoE EXPERTISSUES (NMP3--CTCT- -2004 2004 --500283). 500283info:eu-repo/semantics/publishedVersio

Global Monopole in General Relativity

We consider the gravitational properties of a global monopole on the basis of the simplest Higgs scalar triplet model in general relativity. We begin with establishing some common features of hedgehog-type solutions with a regular center, independent of the choice of the symmetry-breaking potential. There are six types of qualitative behavior of the solutions; we show, in particular, that the metric can contain at most one simple horizon. For the standard Mexican hat potential, the previously known properties of the solutions are confirmed and some new results are obtained. Thus, we show analytically that solutions with monotonically growing Higgs field and finite energy in the static region exist only in the interval $1<\gamma <3$, $\gamma$ being the squared energy of spontaneous symmetry breaking in Planck units. The cosmological properties of these globally regular solutions apparently favor the idea that the standard Big Bang might be replaced with a nonsingular static core and a horizon appearing as a result of some symmetry-breaking phase transition on the Planck energy scale. In addition to the monotonic solutions, we present and analyze a sequence of families of new solutions with oscillating Higgs field. These families are parametrized by $n$, the number of knots of the Higgs field, and exist for $\gamma < \gamma_n = 6/[(2n+1) (n+2)]$; all such solutions possess a horizon and a singularity beyond it.Comment: 14 pages, 8 figure

Thermodynamics of Black Holes in Two (and Higher) Dimensions

A comprehensive treatment of black hole thermodynamics in two-dimensional dilaton gravity is presented. We derive an improved action for these theories and construct the Euclidean path integral. An essentially unique boundary counterterm renders the improved action finite on-shell, and its variational properties guarantee that the path integral has a well-defined semi-classical limit. We give a detailed discussion of the canonical ensemble described by the Euclidean partition function, and examine various issues related to stability. Numerous examples are provided, including black hole backgrounds that appear in two dimensional solutions of string theory. We show that the Exact String Black Hole is one of the rare cases that admits a consistent thermodynamics without the need for an external thermal reservoir. Our approach can also be applied to certain higher-dimensional black holes, such as Schwarzschild-AdS, Reissner-Nordstrom, and BTZ.Comment: 63 pages, 3 pdf figures, v2: added reference

A multi-scale hierarchical framework for developing understanding of river behaviour to support river management

The work leading to this paper was funded through the European Union’s FP7 programme under Grant Agreement No. 282656 (REFORM). The framework methodology was developed within the context of Deliverable D2.1 of the REFORM programme, and all partners who contributed to the development of the four parts of this deliverable are included in the author list of this paper. More details on the REFORM framework can be obtained from part 1 of Deliverable D2.1 (Gurnell et al. 2014), which is downloadable from http://​www.​reformrivers.​eu/​results/​deliverables

Grain refinement of magnesium alloys: a review of recent research, theoretical developments and their application

This paper builds on the ‘‘Grain Refinement of Mg Alloys’’ published in 2005 and reviews the grain refinement research onMg alloys that has been undertaken since then with an emphasis on the theoretical and analytical methods that have been developed. Consideration of recent research results and current theoretical knowledge has highlighted two important factors that affect an alloy’s as-cast grain size. The first factor applies to commercial Mg-Al alloys where it is concluded that impurity and minor elements such as Fe and Mn have a substantially negative impact on grain size because, in combination with Al, intermetallic phases can be formed that tend to poison the more potent native or deliberately added nucleant particles present in the melt. This factor appears to explain the contradictory experimental outcomes reported in the literature and suggests that the search for a more potent and reliable grain refining technology may need to take a different approach. The second factor applies to all alloys and is related to the role of constitutional supercooling which, on the one hand, promotes grain nucleation and, on the other hand, forms a nucleation-free zone preventing further nucleation within this zone, consequently limiting the grain refinement achievable, particularly in low solute-containing alloys. Strategies to reduce the negative impact of these two factors are discussed. Further, the Interdependence model has been shown to apply to a broad range of casting methods from slow cooling gravity die casting to fast cooling high pressure die casting and dynamic methods such as ultrasonic treatment

Novel analgesic/anti-inflammatory agents: 1,5-Diarylpyrrole nitrooxyethyl sulfides and related compounds as Cyclooxygenase-2 inhibitors containing a nitric oxide donor moiety endowed with vasorelaxant properties

The design of compounds able to combine the selective inhibition of cyclooxygenase-2 (COX-2) with the release of nitric oxide (NO) is a promising strategy to achieve potent anti-inflammatory agents endowed with an overall safer profile and reduced toxicity upon gastrointestinal and cardiovascular systems. With the aim of generating novel and selective COX-2 inhibiting NO-donors (CINOD) and encouraged by the promising results obtained with our nitrooxy- and hydroxyethyl ethers 11 and 12 reported in previous works, we shifted our attention on the synthesis of isosteric thioanalogs nitrooxy- and hydroxy ethyl sulfides 13a-c and 14a-c, respectively, along with their oxidation products nitrooxy- and hydroxyethyl sulfoxides 15a-c and 16a-c, respectively, also referred to as thio-CINOD. Preliminary data and metabolic analysis highlighted how the isosteric substitution of the ethereal oxygen atom of 11a-c with sulfur in compounds 13a-c, independently from the presence and the number of fluorine atoms in N1-phenyl ring, leads to new selective and highly potent COX-2 inhibitors, capable to induce vasorelaxant responses in vivo. The same behavior is observed with their oxidized counterparts nitrooxyethyl sulfoxides 15a-c, in which the oxidation state of the sulfur atom and the presence of the additional oxygen atom play a substantial role in enhancing compounds activity and vasorelaxation. In addition, the screened compounds proved significantly efficacious in mouse models of inflammation and nociception at the dose of 20 mg/kg