4,366 research outputs found
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
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
- …