Non-Gaussian fluctuations in stochastic models with absorbing barriers

The dynamics of a one-dimensional stochastic model is studied in presence of an absorbing boundary. The distribution of fluctuations is analytically characterized within the generalized van Kampen expansion, accounting for higher order corrections beyond the conventional Gaussian approximation. The theory is shown to successfully capture the non Gaussian traits of the sought distribution returning an excellent agreement with the simulations, for {\it all times} and arbitrarily {\it close} to the absorbing barrier. At large times, a compact analytical solution for the distribution of fluctuations is also obtained, bridging the gap with previous investigations, within the van Kampen picture and without resorting to alternative strategies, as elsewhere hypothesized.Comment: 2 figures, submitted to Phys. Rev. Let

Can a microscopic stochastic model explain the emergence of pain cycles in patients?

A stochastic model is here introduced to investigate the molecular mechanisms which trigger the perception of pain. The action of analgesic drug compounds is discussed in a dynamical context, where the competition with inactive species is explicitly accounted for. Finite size effects inevitably perturb the mean-field dynamics: Oscillations in the amount of bound receptors spontaneously manifest, driven by the noise which is intrinsic to the system under scrutiny. These effects are investigated both numerically, via stochastic simulations and analytically, through a large-size expansion. The claim that our findings could provide a consistent interpretative framework to explain the emergence of cyclic behaviors in response to analgesic treatments, is substantiated.Comment: J. Stat. Mech. (Proceedings UPON2008

Stochastic Turing Patterns on a Network

The process of stochastic Turing instability on a network is discussed for a specific case study, the stochastic Brusselator model. The system is shown to spontaneously differentiate into activator-rich and activator-poor nodes, outside the region of parameters classically deputed to the deterministic Turing instability. This phenomenon, as revealed by direct stochastic simulations, is explained analytically, and eventually traced back to the finite size corrections stemming from the inherent graininess of the scrutinized medium.Comment: The movies referred to in the paper are provided upon request. Please send your requests to Duccio Fanelli ([email protected]) or Francesca Di Patti ([email protected]

Lactoferrin's anti-cancer properties. Safety, selectivity, and wide range of action

Despite recent advances in cancer therapy, current treatments, including radiotherapy, chemotherapy, and immunotherapy, although beneficial, present attendant side effects and long-term sequelae, usually more or less affecting quality of life of the patients. Indeed, except for most of the immunotherapeutic agents, the complete lack of selectivity between normal and cancer cells for radio- and chemotherapy can make them potential antagonists of the host anti-cancer self-defense over time. Recently, the use of nutraceuticals as natural compounds corroborating anti-cancer standard therapy is emerging as a promising tool for their relative abundance, bioavailability, safety, low-cost effectiveness, and immuno-compatibility with the host. In this review, we outlined the anti-cancer properties of Lactoferrin (Lf), an iron-binding glycoprotein of the innate immune defense. Lf shows high bioavailability after oral administration, high selectivity toward cancer cells, and a wide range of molecular targets controlling tumor proliferation, survival, migration, invasion, and metastasization. Of note, Lf is able to promote or inhibit cell proliferation and migration depending on whether it acts upon normal or cancerous cells, respectively. Importantly, Lf administration is highly tolerated and does not present significant adverse effects. Moreover, Lf can prevent development or inhibit cancer growth by boosting adaptive immune response. Finally, Lf was recently found to be an ideal carrier for chemotherapeutics, even for the treatment of brain tumors due to its ability to cross the blood-brain barrier, thus globally appearing as a promising tool for cancer prevention and treatment, especially in combination therapies

Changes of Inflammatory Mediators in Obese Patients After Laparoscopic Cholecystectomy

Background Obesity is associated with the impairment of immunological functions. The aim of this study was to analyze some inflammatory mediators in obese subjects who underwent laparoscopic cholecystectomy. Methods Seventeen consecutive female patients with a BMI ranging from 35 to 45 kg/m2 (obese) and 17 consecutive female patients with BMI ranging from 20 to 25 kg/m2 (nonobese) were included in the study. All patients were affected by symptomatic gallbladder stone disease and underwent laparoscopic cholecystectomy. Changes in levels of leukocytes, neutrophils, IL-6, IL-10, leptin, and adiponectin were evaluated. Results We observed a significant increase in leukocyte and neutrophil levels in the obese subjects compared to the nonobese subjects. The serum levels of leptin and IL-6 were higher in the postoperative period (compared to the baseline values in both groups), and always higher in the obese. Both adiponectin and IL-10 increased in the postoperative period in nonobese subjects and was always higher than in the obese. Conclusions Obese patients have a stronger acute inflammatory response than do nonobese subjects in reaction to surgical stress

Age-related changes in human ceruloplasmin. Evidence for oxidative modifications.

Human plasma or serum from donors of age comprised between 15 and 95 years was analyzed for paramagnetic and total copper content, as well as for immunoreactive ceruloplasmin content and oxidase activity. All parameters were essentially unaltered, except the paramagnetic copper content, which increased 2-fold upon aging. A dramatic change of the electron paramagnetic resonance spectrum due to ceruloplasmin occurred in individuals over 65 years old and was associated with both an increase of the type 1 copper signal intensity and the appearance of new resonances of a type 2 copper species. Ceruloplasmin was isolated from either young or old donors. Spectroscopic analyses of the isolated proteins confirmed the tendency of type 1 copper to stay reduced in the "young" and oxidized in the "old" protein. The type 2 copper signal observed in most young ceruloplasmin samples was different from the species invariably present in the old protein. The magnetic parameters of the latter species were more consistent with a partially reduced trinuclear copper site. In vitro limited proteolysis resulted in identical fragmentation patterns and kinetics in both proteins. However, changes of the net electric charge were detected in the fragments of the protein isolated from aged individuals, which exhibited a carbonyl content of 0.6 mol of carbonyl/mol of protein. The same pattern of modifications, including a higher carbonyl content (0.65 versus 0.2 mol of carbonyl/mol of protein), could be reproduced by exposure of the young protein to the metal-catalyzed oxidation system iron/ascorbate. These results suggest that during aging ceruloplasmin is subjected to oxidative modifications which are likely to be the source of conformational changes around the copper sites leading to an intramolecular electron rearrangement among the various copper sites

Zero and Finite Temperature Quantum Simulations Powered by Quantum Magic

We present a comprehensive approach to quantum simulations at both zero and finite temperatures, employing a quantum information theoretic perspective and utilizing the Clifford + $k$Rz transformations. We introduce the "quantum magic ladder", a natural hierarchy formed by systematically augmenting Clifford transformations with the addition of Rz gates. These classically simulable similarity transformations allow us to reduce the quantumness of our system, conserving vital quantum resources. This reduction in quantumness is essential, as it simplifies the Hamiltonian and shortens physical circuit-depth, overcoming constraints imposed by limited error correction. We improve the performance of both digital and analog quantum computers on ground state and finite temperature molecular simulations, not only outperforming the Hartree-Fock solution, but also achieving consistent improvements as we ascend the quantum magic ladder. By facilitating more efficient quantum simulations, our approach enables near-term and early fault-tolerant quantum computers to address novel challenges in quantum chemistry.Comment: 12 pages, 9 figure

All-oral metronomic DEVEC schedule in elderly patients with peripheral T cell lymphoma

Purpose: Peripheral T cell lymphomas (PTCLs) have an overall poor prognosis. Indeed, registry data in elderly patients show that the median progression-free survival (mPFS) following first- and second-line therapies are only 6.7 and 3.1 months, respectively. The aim of the study is to show the activity of metronomic chemotherapy, a regular administration of low chemotherapeutic drug doses allowing a favourable toxicity profile, on elderly PTCL patients. Methods: We report a series of 17 PTCL patients, treated with the all-oral metronomic schedule DEVEC (prednisolone–etoposide–vinorelbine–cyclophosphamide) in four Italian centres. Patients 5/17 (29.4%) were treatment-naïve (naïve) and 12/17 (70.6%) were relapsed-refractory (RR), respectively. The median age was 83 years (range 71–87) and 71.5 years (range 56–85) for naïve and RR, respectively. In vitro activity of metronomic vinorelbine (VNR), etoposide (ETO) and their concomitant combination on HH, a PTCL cell line, was also assessed. Results: Histology: PTCL-not-otherwise-specified = 12; angioimmunoblastic = 2; NK/T nasal type = 1; adult-type leukaemia lymphoma = 1, transformed Mycosis Fungoides = 1. The overall response rate was 80 and 58% in naïve and RR, respectively; whereas the PFS was 20 in naïve (95% CI 0–43) and 11 months (95% CI 4.2–17.8) in RR. The occurrence of relevant adverse events was 23.5%, which was managed with ETO dose reduction. In vitro experiments showed that both metronomic VNR and ETO caused a significant inhibitory activity on HH cells and a strong synergism when administered concomitantly. Conclusion: All-oral DEVEC showed an encouraging activity and acceptable toxicity. This schedule deserves further studies in elderly PTCL also for assessing combinations with targeted drugs

A spatial model of autocatalytic reactions

Biological cells with all of their surface structure and complex interior stripped away are essentially vesicles - membranes composed of lipid bilayers which form closed sacs. Vesicles are thought to be relevant as models of primitive protocells, and they could have provided the ideal environment for pre-biotic reactions to occur. In this paper, we investigate the stochastic dynamics of a set of autocatalytic reactions, within a spatially bounded domain, so as to mimic a primordial cell. The discreteness of the constituents of the autocatalytic reactions gives rise to large sustained oscillations, even when the number of constituents is quite large. These oscillations are spatio-temporal in nature, unlike those found in previous studies, which consisted only of temporal oscillations. We speculate that these oscillations may have a role in seeding membrane instabilities which lead to vesicle division. In this way synchronization could be achieved between protocell growth and the reproduction rate of the constituents (the protogenetic material) in simple protocells.Comment: Submitted to Phys. Rev.