927 research outputs found
Roughening of the anharmonic Larkin model
We study the roughening of d-dimensional directed elastic interfaces subject to quenched random forces. As in the Larkin model, random forces are considered constant in the displacement direction and uncorrelated in the perpendicular direction. The elastic energy density contains an harmonic part, proportional to (âxu)2, and an anharmonic part, proportional to (âxu)2n, where u is the displacement field and n>1 an integer. By heuristic scaling arguments, we obtain the global roughness exponent ζ, the dynamic exponent z, and the harmonic to anharmonic crossover length scale, for arbitrary d and n, yielding an upper critical dimension dc(n)=4n. We find a precise agreement with numerical calculations in d=1. For the d=1 case we observe, however, an anomalous "faceted" scaling, with the spectral roughness exponent ζs satisfying ζs>ζ>1 for any finite n>1, hence invalidating the usual single-exponent scaling for two-point correlation functions, and the small gradient approximation of the elastic energy density in the thermodynamic limit. We show that such d=1 case is directly related to a family of Brownian functionals parameterized by n, ranging from the random-acceleration model for n=1 to the LĂ©vy arcsine-law problem for n=â. Our results may be experimentally relevant for describing the roughening of nonlinear elastic interfaces in a Matheron-de Marsilly type of random flow.Fil: Purrello, VĂctor Hugo. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - Mar del Plata. Instituto de Investigaciones FĂsicas de Mar del Plata. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones FĂsicas de Mar del Plata; ArgentinaFil: Iguain, Jose Luis. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - Mar del Plata. Instituto de Investigaciones FĂsicas de Mar del Plata. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones FĂsicas de Mar del Plata; ArgentinaFil: Kolton, Alejandro Benedykt. ComisiĂłn Nacional de EnergĂa AtĂłmica. Gerencia del Ărea de EnergĂa Nuclear. Instituto Balseiro; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; Argentin
Absorption flattening as one cause of distortion of circular dichroism spectra of Delta-RuPhen(3) . H(2)TPPS complex
To extend the model that explains why and how much absorption flattening
(AF) influences circular dichroism (CD) signals, we have investigated the interesting
case of exciton CD in the Soret region of a noncovalent complex formed by (DRuPhen3)
21 and the tetraanionic porphyrin H2TPPS. Different concentrations have been
studied by using an AF emulator and spectra simulation. The CD spectra of this compound
occasionally show distortions in the solution sampling mode with the increase of
concentration; the inhomogeneous distribution in the cell volume is due to aggregation
and is the source of the AF effect. On the basis of these results, we conclude that AF is
an important cause of distortions in CD spectra for D-RuPhen3 H2TPPS complexes and
might affect the CD bands of other aggregated systems as wel
Hysteretic depinning of a particle in a periodic potential: Phase diagram and criticality
We consider a massive particle driven with a constant force in a periodic
potential and subjected to a dissipative friction. As a function of the drive
and damping, the phase diagram of this paradigmatic model is well known to
present a pinned, a sliding, and a bistable regime separated by three distinct
bifurcation lines. In physical terms, the average velocity of the particle
is nonzero only if either (i) the driving force is large enough to remove any
stable point, forcing the particle to slide, or (ii) there are local minima but
the damping is small enough, below a critical damping, for the inertia to allow
the particle to cross barriers and follow a limit cycle; this regime is
bistable and whether or depends on the initial state. In this
paper, we focus on the asymptotes of the critical line separating the bistable
and the pinned regimes. First, we study its behavior near the "triple point"
where the pinned, the bistable, and the sliding dynamical regimes meet. Just
below the critical damping we uncover a critical regime, where the line
approaches the triple point following a power-law behavior. We show that its
exponent is controlled by the normal form of the tilted potential close to its
critical force. Second, in the opposite regime of very low damping, we revisit
existing results by providing a simple method to determine analytically the
exact behavior of the line in the case of a generic potential. The analytical
estimates, accurately confirmed numerically, are obtained by exploiting exact
soliton solutions describing the orbit in a modified tilted potential which can
be mapped to the original tilted washboard potential. Our methods and results
are particularly useful for an accurate description of underdamped nonuniform
oscillators driven near their triple point.Comment: 13 pages, 13 figures, published versio
Comparative effectiveness of dapagliflozin vs DPP-4 inhibitors on a composite endpoint of HbA1c, body weight and blood pressure reduction in the real world
Background: Treatment of type 2 diabetes (T2D) should aim at preventing or delaying complications through the control of glycaemia and cardiovascular risk factors. We herein compared the SGLT-2 inhibitor dapagliflozin vs DPP-4 inhibitors (DPP-4i) on a composite endpoint of glycaemic and extraglycaemic effectiveness. Methods: This was a multicentre, retrospective real-world study conducted at 56 outpatient clinics in Italy. We collected data on patients newly started on dapagliflozin or DPP-4i in 2015-2017. The primary endpoint was the proportion of patients attaining a simultaneous reduction of HbA1c â„0.5%, body weight â„2 kg, systolic blood pressure (SBP) â„2 mmHg. Confounding by indication was addressed by propensity score matching (PSM) or multivariable adjustment (MVA). Results: Patients initiating dapagliflozin (n = 2091) or DPP-4i (n = 2144) differed for most clinical characteristics. After PSM, two well-balanced groups of 1149 patients each were compared. The primary endpoint was reached in a greater proportion of patients who received dapagliflozin (17.6%) compared to DPP-4i (11.7%), with a relative risk of 1.50 (1.21-1.86; P <.001). Similar results were obtained in the as-treated and intention-to-treat datasets or using MVA in place of PSM. The beneficial effect of dapagliflozin was mainly due to its greater effectiveness on body weight and, to a lesser extent, on SBP. The change in HbA1c did not differ between groups. Conclusions: T2D patients initiating the SGLT2i dapagliflozin had a greater probability of attaining a composite endpoint of clinically relevant reductions in HbA1c, body weight and SBP, compared to similar patients initiating a DPP-4i in the same period and healthcare setting
Cellular and molecular effects of protons: apoptosis induction and potential implications for cancer therapy.
Due to their ballistic precision, apoptosis induction by protons could be a strategy to specifically eliminate neoplastic cells. To characterize the cellular and molecular effects of these hadrons, we performed dose-response and time-course experiments by exposing different cell lines (PC3, Ca301D, MCF7) to increasing doses of protons and examining them with FACS, RT-PCR, and electron spin resonance (ESR). Irradiation with a dose of 10 Gy of a 26,7 Mev proton beam altered cell structures such as membranes, caused DNA double strand breaks, and significantly increased intracellular levels of hydroxyl ions, are active oxygen species (ROS). This modified the transcriptome of irradiated cells, activated the mitochondrial (intrinsic) pathway of apoptosis, and resulted in cycle arrest at the G2/M boundary. The number of necrotic cells within the irradiated cell population did not significantly increase with respect to the controls. The effects of irradiation with 20 Gy were qualitatively as well as quantitatively similar, but exposure to 40 Gy caused massive necrosis. Similar experiments with photons demonstrated that they induce apoptosis in a significantly lower number of cells and in a temporally delayed manner. These data advance our knowledge on the cellular and molecular effects of proton irradiation and could be useful for improving current hadrontherapy protocols
a consensus statement for the clinical use of the renal sodium glucose co transporter 2 inhibitor dapagliflozin in patients with type 2 diabetes mellitus
ABSTRACTIntroduction: The present review developed a clinical consensus based on a Delphi method on Dapagliflozin, a selective inhibitor of the renal sodium-glucose co-transporter-2 (SGLT2-I) in the treatment of patients with Type 2 diabetes mellitus.Areas covered: Panel members, using a 5-point scale, were asked to rate 9 statements on pharmakodinamic, mode of action on glycaemic and extra-glycaemic effects, and safety of dapaglifozin, Members also aimed to identify the patient most susceptible to the treatment with dapagliflozin .Expert commentary: Dapagliflozin is effective in lowering the plasma glucose concentration with a good safety profile. Dapagliflozin can be utilized in combination with all other antihyperglycaemic agents at all stages of the disease: however, a reduced GFR limits its efficacy. As for the other drugs of the class, Dapagliflozin positively modifies other risk factors for CV disease: these effects will be tested in the so far largest cardiovascular outcome trial for the SGLT2 inh..
Cationic porphyrins are reversible proteasome inhibitors
The aim of this study is to verify if watersoluble porphyrins can be used as proteasome inhibitors. We have found that cationic porphyrins inhibit proteasome peptidase activities much more effectively than the corresponding anionic derivatives. The relevance of electrostatics in driving porphyin−proteasome interactions has been confirmed by the observation that the inhibitory efficiency of the cationic macrocycles decreases with the number of positive substituents. We have also investigated various metalloporphyrins, which differ due to the different propension of the central metal ion toward axial coordination. Our experimental results indicate that the naked cationic porphyrins are the most active in reversibly inhibiting the three main protease activities of the proteasome in the micromolar range. A spectroscopic characterization of porphyrin−proteasome interactions by UV−vis spectra parallels the results of inhibition assays: the higher the inhibitory effect the stronger the spectroscopic variations are. To interpret the action of porphyrins at a molecular level, we have performed calculations evidencing that cationic porphyrins may hinder the access to the canonical proteolytic site on the proteasome β5 subunit. In particular, an inspection of the top-scoring docking modes shows that the tetracationic porphyrin blocks the catalytic pocket, close to the N termini of the β5 proteasome subunit, more efficiently than its anionic counterpart. Proteasome inhibition activity of porphyrins unites their known anticancer properties making them suitable as a scaffold for the design of novel multitargeted molecules
Multi-disciplinary Consensus Statement Document Vaccinal prevention in adult patients with diabetes mellitus
open8noopenIcardi G.; Francia F.; Di Bartolo P.; Mannino D.; Alti E.; Purrello F.; Sesti G.; Sessa A.Icardi, G.; Francia, F.; Di Bartolo, P.; Mannino, D.; Alti, E.; Purrello, F.; Sesti, G.; Sessa, A
Design principles of chiral carbon nanodots help convey chirality from molecular to nanoscale level
The chirality of (nano)structures is paramount in many phenomena, including biological processes, self-assembly, enantioselective reactions, and light or electron spin polarization. In the quest for new chiral materials, metallo-organic hybrids have been attractive candidates for exploiting the aforementioned scientific fields. Here, we show that chiral carbon nanoparticles, called carbon nanodots, can be readily prepared using hydrothermal microwave-assisted synthesis and easily purified. These particles, with a mean particle size around 3ânm, are highly soluble in water and display mirror-image profile both in the UVâVis and in the infrared regions, as detected by electronic and vibrational circular dichroism, respectively. Finally, the nanoparticles are used as templates for the formation of chiral supramolecular porphyrin assemblies, showing that it is possible to use and transfer the chiral information. This simple (and effective) methodology opens up exciting opportunities for developing a variety of chiral composite materials and applications
- âŠ