3,016 research outputs found
Comparisons of Hyv\"arinen and pairwise estimators in two simple linear time series models
The aim of this paper is to compare numerically the performance of two
estimators based on Hyv\"arinen's local homogeneous scoring rule with that of
the full and the pairwise maximum likelihood estimators. In particular, two
different model settings, for which both full and pairwise maximum likelihood
estimators can be obtained, have been considered: the first order
autoregressive model (AR(1)) and the moving average model (MA(1)). Simulation
studies highlight very different behaviours for the Hyv\"arinen scoring rule
estimators relative to the pairwise likelihood estimators in these two
settings.Comment: 14 pages, 2 figure
Targeting Brutons Tyrosine Kinase in Chronic Lymphocytic Leukemia at the Crossroad between Intrinsic and Extrinsic Pro-survival Signals
Chemo immunotherapies for chronic lymphocytic leukemia (CLL) showed a positive impact on clinical outcome, but many patients relapsed or become refractory to the available treatments. The main goal of the researchers in CLL is the identification of specific targets in order to develop new therapeutic strategies to cure the disease. The B cell receptor-signalling pathway is necessary for survival of malignant B cells and its related molecules recently become new targets for therapy. Moreover, leukemic microenvironment delivers survival signals to neoplastic cells also overcoming the apoptotic effect induced by traditional drugs. In this context, the investigation of Bruton\u2019s tyrosine kinase (Btk) is useful in: i) dissecting CLL pathogenesis; ii) finding new therapeutic approaches striking simultaneously intrinsic as well as extrinsic pro-survival signals in CLL. This paper will review these main topics
Study of network composition in interpenetrating polymer networks of poly(N isopropylacrylamide) microgels:the role of poly(acrylic acid)
Hypothesis: The peculiar swelling behaviour of poly(N-isopropylacrylamide)
(PNIPAM)-based responsive microgels provides the possibility to tune both
softness and volume fraction with temperature, making these systems of great
interest for technological applications and theoretical implications. Their
intriguing phase diagram can be even more complex if poly(acrylic acid) (PAAc)
is interpenetrated within PNIPAM network to form Interpenetrating Polymer
Network (IPN) microgels that exhibit an additional pH-sensitivity. The effect
of the PAAc/PNIPAM polymeric ratio on both swelling capability and dynamics is
still matter of investigation. Experiments: Here we investigate the role of
PAAc in the behaviour of IPN microgels across the volume phase transition
through dynamic light scattering (DLS), transmission electron microscopy (TEM)
and electrophoretic measurements as a function of microgel concentration and
pH. Findings: Our results highlight that aggregation is favored at increasing
weight concentration, PAAc content and pH and that a crossover PAAc content
C*_{PAAc} exists above which the ionic charges on the microgel become relevant.
Moreover we show that the softness of IPN microgels can be tuned ad hoc by
changing the PAAc/PNIPAM ratio. These findings provide new insights into the
possibility to control experimentally aggregation properties, charge and
softness of IPN microgels by varying PAAc content.Comment: preprint versio
Molecular mechanisms driving the microgels behaviour: a Raman spectroscopy and Dynamic Light Scattering study
Responsive microgels based on poly(N-isopropylacrylamide) (PNIPAM) exhibit
peculiar behaviours due to the competition between the hydrophilic and
hydrophobic interactions of the constituent networks. The interpenetration of
poly-acrilic acid (PAAc), a pH-sensitive polymer, within the PNIPAM network, to
form Interpenetrated Polymer Network (IPN) microgels, affects this delicate
balance and the typical Volume-Phase Transition (VPT) leading to complex
behaviours whose molecular nature is still completely unexplored. Here we
investigate the molecular mechanism driving the VPT and its influence on
particle aggregation for PNIPAM/PAAc IPN microgels by the joint use of Dynamic
Light Scattering and Raman Spectroscopy. Our results highlight that PNIPAM
hydrophobicity is enhanced by the interpenetration of PAAc promoting
interparticle interactions, a crossover concentration is found above which
aggregation phenomena become relevant. Moreover we find that, at variance with
PNIPAM, for IPN microgels a double-step molecular mechanisms occurs upon
crossing the VPT, the first involving the coil-to-globule transition typical of
PNIPAM and the latter associated to PAAc steric hindrance.Comment: preprint versio
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