Temsirolimus in the treatment of relapsed and/or refractory mantle cell lymphoma

Patients with mantle cell lymphoma (MCL) have a poor prognosis; consequently, new therapeutic approaches, such as rapamycin and its derivates, mammalian target of rapamycin (mTOR) inhibitors, are warranted. Temsirolimus (also known as CCI-779), a dihydroester of rapamycin, in MCL cell lines inhibited mTOR, downregulated p21 and v-Raf, and induced autophagy. The first clinical trial in MCL patients was performed using 250 mg of temsirolimus weekly for 6–12 cycles. The overall response rate was 38%; the median time to progression was 6.5 months, median overall survival was 12 months, and the median duration of response was 6.9 months. At lower dose (25 mg/week), the overall response rate was 41%, median overall survival was 14 months, and time to progression was 6 months. In another trial, 162 patients were randomly assigned to receive temsirolimus at 2 different doses (175 mg/week for 3 weeks, then 75 mg or 25 mg/week) or a treatment chosen by the investigator among the most frequently adopted single agents for treatment of relapsed MCL. Patients treated with 175/75 mg of temsirolimus had significantly higher response rates and longer progression-free survival than those treated with investigator’s choice therapy. These data support the use of mTOR inhibitors for the treatment of MCL, probably in combination with other agents, such as antiangiogenic drugs or histone acetylase inhibitors

Application of novel techniques for interferogram analysis to laser-plasma femtosecond probing

Recently, two novel techniques for the extraction of the phase-shift map (Tomassini {\it et.~al.}, Applied Optics {\bf 40} 35 (2001)) and the electronic density map estimation (Tomassini P. and Giulietti A., Optics Communication {\bf 199}, pp 143-148 (2001)) have been proposed. In this paper we apply both methods to a sample laser-plasma interferogram obtained with femtoseconds probe pulse, in an experimental setup devoted to laser particle acceleration studies.Comment: Submitted to Laser and Particle Beam

Functionalized carbon black for elastomer composites with low hysteresis

The prime application of elastomeric composites is tire compounds. The tuning of dynamic rigidity and hysteresis is key to achieve the desired tire performances. Car tires require hysteresis to be high at low temperatures, to promote wet traction, and low at medium-high temperatures, for low energy dissipations. To achieve these properties amorphous precipitated silica is commonly selected as reinforcing filler due to its nano dimensions and the possibility of establishing chemical bonds with the elastomers’ chains. Carbon black (CB), another common filler for tire compounds, does not have functional groups able to promote chemical bonds with the rubber matrix yet it would be highly desirable. A CB with a cradle to gate LCA comparable if not even better than silica’s LCA could be used in replacement of silica in tire compounds. In this work, a pyrrole compound (PyC) containing a thiol group was used to functionalize CB by the so-called “pyrrole methodology” . The thiol group was expected to react with the sulphur-based crosslinking system, thus forming chemical bonds with the rubber chains. The synthesis of the PyC and the functionalization reaction were characterized by high atom efficiency. A poly(styrene-co-butadiene) copolymer from anionic solution polymerization was used as the main rubber for the compound preparation. The crosslinked composite material filled with functionalized CB revealed substantial improvements with respect to the composite with pristine CB, in particular: high rigidity and low hysteresis at high temperature. These findings seem to confirm the formation of the expected rubber-filler chemical bond and are even comparable to those of silica- based rubber composites. The results here reported pave the way to CB-based rubber composites with a low environmental impact

Semiparametric finite mixture of regression models with Bayesian P-splines

Mixture models provide a useful tool to account for unobserved heterogeneity and are at the basis of many model-based clustering methods. To gain additional flexibility, some model parameters can be expressed as functions of concomitant covariates. In this Paper, a semiparametric finite mixture of regression models is defined, with concomitant information assumed to influence both the component weights and the conditional means. In particular, linear predictors are replaced with smooth functions of the covariate considered by resorting to cubic splines. An estimation procedure within the Bayesian paradigm is suggested, where smoothness of the covariate effects is controlled by suitable choices for the prior distributions of the spline coefficients. A data augmentation scheme based on difference random utility models is exploited to describe the mixture weights as functions of the covariate. The performance of the proposed methodology is investigated via simulation experiments and two real-world datasets, one about baseball salaries and the other concerning nitrogen oxide in engine exhaust

Functionalized carbon black for elastomeric composites with low dissipation of energy

The most important application of elastomeric composites, tire compounds, relies on the following dynamic-mechanical properties: dynamic rigidity and hysteresis. For car tires, hysteresis is tuned as a function of temperature: high at low temperature and low at medium-high temperature, to promote traction on wet roads and low energy dissipation (rolling resistance), respectively. To obtain these properties, amorphous precipitated silica is used as reinforcing filler. The strengths of silica are: nano dimensions and the possibility of incorporating and establishing chemical bonds with the elastomers’ chains. Carbon black (CB), which is also largely used in tire compounds, does not have functional groups able to promote chemical bonds with the rubber matrix. It would be highly desirable to functionalize the surface of carbon black with such functional groups: a CB with a cradle to gate LCA comparable if not even better than silica’s LCA could be used in replacement of silica in tire compounds. In this work, a pyrrole compound (PyC) was used for functionalizing CB by applying the so-called “pyrrole methodology”. The selected PyC contained a thiol group which was expected to react with the sulphur-based crosslinking system, thus forming chemical bonds with the rubber chains. The synthesis of the PyC and the functionalization reaction were characterized by high atom efficiency. A poly(styrene-co-butadiene) copolymer from anionic solution polymerization was used as the main rubber for the compound preparation. The crosslinked composite material filled with functionalized CB revealed substantial improvements with respect to the composite with pristine CB, in particular: high rigidity and low hysteresis at high temperature. These findings seem to confirm the formation of the expected rubber-filler chemical bond and are even comparable to those of silicabased rubber composites. The results here reported pave the way to CB-based rubber composites with a low environmental impact

A Molecular Dynamics Study of Noncovalent Interactions between Rubber and Fullerenes

The percolation and networking of filler particles is an important issue in the field of rubber reinforcement, and much effort is given to clarify the true nature of the reinforcement mechanism and the viscoelastic behavior. The concentration of nanofillers also in the presence of large amounts of carbon black is a parameter that can influence the macroscopic rubber behavior. In this paper, noncovalent interactions between C60 fullerenes with poly-1,4-cis-isoprene (PI) either as such or modified are studied through atomistic simulations based on molecular mechanics (MM) and molecular dynamics (MD) methods. At first, the conformational properties of a single chain and of 12 PI chains in a periodic simulation box are studied. Afterwards, the conformational properties of a single PI chain polymer terminated with a -COOH group, and then a bulk system formed by chains of unmodified and some PI modified chains are considered. Then, the systems formed by adding fullerenes to these two different bulk systems are studied. Relatively small interaction energy between rubber and fullerenes being well dispersed in the sample is found. The simulations showed a preferential tendency of fullerenes to display self-aggregation, in the presence of even a small fraction of modified polymer chains