A virtual approach to evaluate therapies for management of multiple myeloma induced bone disease: Modelling Therapies for Multiple Myeloma Induced Bone Disease

Multiple myeloma bone disease is devastating for patients and a major cause of morbidity. The disease leads to bone destruction by inhibiting osteoblast activity while stimulating osteoclast activity. Recent advances in multiple myeloma research have improved our understanding of the pathogenesis of multiple myeloma-induced bone disease and suggest several potential therapeutic strategies. However, the effectiveness of some potential therapeutic strategies still requires further investigation and optimization. In this paper, a recently developed mathematical model is extended to mimic and then evaluate three therapies of the disease, namely: bisphosphonates, bortezomib and TGF-β inhibition. The model suggests that bisphosphonates and bortezomib treatments not only inhibit bone destruction, but also reduce the viability of myeloma cells. This contributes to the current debate as to whether bisphosphonate therapy has an anti-tumour effect. On the other hand, the analyses indicate that treatments designed to inhibit TGF-β do not reduce bone destruction, although it appears that they might reduce the viability of myeloma cells, which again contributes to the current controversy regarding the efficacy of TGF-β inhibition in multiple myeloma-induced bone disease

Investigating the efficacy of bisphosphonates treatment against multiple myeloma induced bone disease using a computational model

Multiple myeloma (MM)-induced bone disease is mortal for most MM patients. Bisphosphonates are first-line treatment for MM-induced bone disease, since it can inhibit osteoclast activity and the resultant bone resorption by suppressing the differentiation of osteoclast precursors into mature osteoclasts, promoting osteoclast apoptosis and disrupting osteoclast function. However, it is still unclear whether bisphosphonates have an anti-tumour effect. In our previous work, a computational model was built to simulate the pathology of MM-induced bone disease. This paper extends this proposed computational model to investigate the efficacy of bisphosphonates treatment and then clear the controversy of this therapy. The extended model is validated through the good agreement between simulation results and experimental data. The simulation results suggest that bisphosphonates indeed have an anti-tumour effect

Reactive ion etching of polyimide films using a radio frequency discharge

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Silicon and III-V compound nanotubes: structural and electronic properties

Unusual physical properties of single-wall carbon nanotubes have started a search for similar tubular structures of other elements. In this paper, we present a theoretical analysis of single-wall nanotubes of silicon and group III-V compounds. Starting from precursor graphene-like structures we investigated the stability, energetics and electronic structure of zigzag and armchair tubes using first-principles pseudopotential plane wave method and finite temperature ab-initio molecular dynamics calculations. We showed that (n,0) zigzag and (n,n) armchair nanotubes of silicon having n > 6 are stable but those with n < 6 can be stabilized by internal or external adsorption of transition metal elements. Some of these tubes have magnetic ground state leading to spintronic properties. We also examined the stability of nanotubes under radial and axial deformation. Owing to the weakness of radial restoring force, stable Si nanotubes are radially soft. Undeformed zigzag nanotubes are found to be metallic for 6 < n < 11 due to curvature effect; but a gap starts to open for n > 12. Furthermore, we identified stable tubular structures formed by stacking of Si polygons. We found AlP, GaAs, and GaN (8,0) single-wall nanotubes stable and semiconducting. Our results are compared with those of single-wall carbon nanotubes.Comment: 11 pages, 10 figure

Tailoring Graphene with Metals on Top

We study the effects of metallic doping on the electronic properties of graphene using density functional theory in the local density approximation in the presence of a local charging energy (LDA+U). The electronic properties are sensitive to whether graphene is doped with alkali or transition metals. We estimate the the charge transfer from a single layer of Potassium on top of graphene in terms of the local charging energy of the graphene sheet. The coating of graphene with a non-magnetic layer of Palladium, on the other hand, can lead to a magnetic instability in coated graphene due to the hybridization between the transition-metal and the carbon orbitals.Comment: 5 pages, 4 figure

Functional evolution of the feeding system in rodents

The masticatory musculature of rodents has evolved to enable both gnawing at the incisors and chewing at the molars. In particular, the masseter muscle is highly specialised, having extended anteriorly to originate from the rostrum. All living rodents have achieved this masseteric expansion in one of three ways, known as the sciuromorph, hystricomorph and myomorph conditions. Here, we used finite element analysis (FEA) to investigate the biomechanical implications of these three morphologies, in a squirrel, guinea pig and rat. In particular, we wished to determine whether each of the three morphologies is better adapted for either gnawing or chewing. Results show that squirrels are more efficient at muscle-bite force transmission during incisor gnawing than guinea pigs, and that guinea pigs are more efficient at molar chewing than squirrels. This matches the known diet of nuts and seeds that squirrels gnaw, and of grasses that guinea pigs grind down with their molars. Surprisingly, results also indicate that rats are more efficient as well as more versatile feeders than both the squirrel and guinea pig. There seems to be no compromise in biting efficiency to accommodate the wider range of foodstuffs and the more general feeding behaviour adopted by rats. Our results show that the morphology of the skull and masticatory muscles have allowed squirrels to specialise as gnawers and guinea pigs as chewers, but that rats are high-performance generalists, which helps explain their overwhelming success as a group

Non-collinear coupling between magnetic adatoms in carbon nanotubes

The long range character of the exchange coupling between localized magnetic moments indirectly mediated by the conduction electrons of metallic hosts often plays a significant role in determining the magnetic order of low-dimensional structures. In addition to this indirect coupling, here we show that the direct exchange interaction that arises when the moments are not too far apart may induce a non-collinear magnetic order that cannot be characterized by a Heisenberg-like interaction between the magnetic moments. We argue that this effect can be manipulated to control the magnetization alignment of magnetic dimers adsorbed to the walls of carbon nanotubes.Comment: 13 pages, 5 figures, submitted to PR

Should we use SSRIs to treat adolescents with depression?

Yes. B ased on current evidence, fluoxetine is the most effective selective serotonin reuptake inhibitor (SSRI) for treatment of major depressive disorder in adolescents. It is the only agent approved by the US Food and Drug Administration (FDA) for use in children (strength of recommendation [SOR]: A, based on meta-analysis of RCTs). All SSRI medications increase the risk of suicidal behavior in adolescents, but do not increase the risk of completing suicide (SOR: A, based on meta-analysis of RCTs)

Production of linalool, cis- and trans-nerolidol, and trans,trans-farnesol by Saccharomyces fermentati growing as a film on simulated wine

Linalool, cis-nerolidol, trans-nerolidol, and trans,trans-farnesol are produced in low concentrations by the wine yeast Saccharomyces fermentati growing as a film for 10 weeks on the surface of a simulated fino sherry containing ethanol as the only volatile carbon containing compound. lt is not known whether Saccharomyces cerevisiae also produces terpenes while fermenting grape juice to wine. However, caution seems advisable in differentiating among Vitis vinifera cultivars on the basis of terpenes found in the wines.Die Bildung von Linalool, cis- und trans-Nerolidol sowie trans,trans-Farnesol durch eine Decke von Saccharomyces fermentati auf einem ModellweinDie deckenbildende Form von Saccharomyces fermentati erzeugte im Verlauf von 10 Wochen auf einem simulierten Fino-Sherry, der als einzige flüchtige Kohlenstoffverbindung Äthanol enthielt, geringe Mengen von Linalool, cis-Nerolidol, trans-Nerolidol und trans,trans-Farnesol. Es ist zwar nicht bekannt, ob Saccharomyces cerevisiae bei der Vergärung von Traubensaft ebenfalls Terpene bildet; trotzdem scheint Vorsicht geboten zu sein, wenn Vitis-vinifera-Sorten aufgrund der in den Weinen gefundenen Terpene charakterisiert werden