Noise and diffusion of particles obeying asymmetric exclusion processes

The relation between noise and Fick's diffusion coefficient in barrier limited transport associated with hopping or tunneling mechanisms of particles obeying the asymmetric simple exclusion processes (ASEP) is physically assessed by Monte Carlo simulations. For a closed ring consisting of a large number of barriers the diffusion coefficient is related explicitly to the current noise thus revealing the existence of a generalized Nyquist-Einstein relation. Both diffusion and noise are confirmed to decrease as the square root of the number of barriers as a consequence of the correlation induced by ASEP. By contrast, for an open linear chain of barriers the diffusion coefficient is found to be no longer related to current noise. Here diffusion depends on particle concentration but is independent of the number of barriers

Practical use of blactchford score

Aim: To retrospectively evaluate the use of proton pump inhibitor infusions. Methods: A retrospective chart review was conducted of all patients who received an 80 mg bolus of esomeprazole follow by an infusion at 8 mg/hr. An analysis was performed to determine if a Blatchford Score of \u3e 5 was a predictor of upper gastrointestinal ulcers. Results: 300 patients received high dose esomeprazole over a 15 month period. 32% had an ulcer identified on endoscopy. Gastritis and esophagitis were the second most common diagnosis accounting for 16% of patients. A Blatchford Score of \u3e5 as a predictor of upper gastrointestinal ulcers had a sensitivity of 86.5% with a specificity of 32%. Conclusion: Utilizing the Blatchford Score to predict patients that have an upper gastrointestinal ulcer does not appear to be effective in clinical practice

Polyamine–Drug Conjugates: Do They Boost Drug Activity?

Over the past two decades, the strategy of conjugating polyamine tails with bioactive molecules such as anticancer and antimicrobial agents, as well as antioxidant and neuroprotective scaffolds, has been widely exploited to enhance their pharmacological profile. Polyamine transport is elevated in many pathological conditions, suggesting that the polyamine portion could improve cellular and subcellular uptake of the conjugate via the polyamine transporter system. In this review, we have presented a glimpse on the polyamine conjugate scenario, classified by therapeutic area, of the last decade with the aim of highlighting achievements and fostering future developments

Stability and Total Variation Estimates on General Scalar Balance Laws

Consider the general scalar balance law \partial_t u + \Div f(t, x,u) = F(t,x,u) in several space dimensions. The aim of this note is to estimate the dependence of its solutions from the flow $f$ and from the source $F$. To this aim, a bound on the total variation in the space variables of the solution is obtained. This result is then applied to obtain well posedness and stability estimates for a balance law with a non local source

Eye-Light on Age-Related Macular Degeneration: Targeting Nrf2-Pathway as a Novel Therapeutic Strategy for Retinal Pigment Epithelium

open6noThis work was supported by the University of Pavia [to MA, grant number BSR1744747; 2017] and the Italian Ministry of University and Research [to MA, FFABR2017]. The University of Bologna is acknowledged by MR [Grants from RFO].Age-related macular degeneration (AMD) is a common disease with a multifactorial aetiology, still lacking effective and curative therapies. Among the early events triggering AMD is the deterioration of the retinal pigment epithelium (RPE), whose fundamental functions assure good health of the retina. RPE is physiologically exposed to high levels of oxidative stress during its lifespan; thus, the integrity and well-functioning of its antioxidant systems are crucial to maintain RPE homeostasis. Among these defensive systems, the Nrf2-pathway plays a primary role. Literature evidence suggests that, in aged and especially in AMD RPE, there is an imbalance between the increased pro-oxidant stress, and the impaired endogenous detoxifying systems, finally reverberating on RPE functions and survival. In this in vitro study on wild type (WT) and Nrf2-silenced (siNrf2) ARPE-19 cells exposed to various AMD-related noxae (H2O2, 4-HNE, MG132 + Bafilomycin), we show that the Nrf2-pathway activation is a physiological protective stress response, leading downstream to an up-regulation of the Nrf2-targets HO1 and p62, and that a Nrf2 impairment predisposes the cells to a higher vulnerability to stress. In search of new pharmacologically active compounds potentially useful for AMD, four nature-inspired hybrids (NIH) were individually characterized as Nrf2 activators, and their pharmacological activity was investigated in ARPE-19 cells. The Nrf2 activator dimethyl-fumarate (DMF; 10 μM) was used as a positive control. Three out of the four tested NIH (5 μM) display both direct and indirect antioxidant properties, in addition to cytoprotective effects in ARPE-19 cells under pro-oxidant stimuli. The observed pro-survival effects require the presence of Nrf2, with the exception of the lead compound NIH1, able to exert a still significant, albeit lower, protection even in siNrf2 cells, supporting the concept of the existence of both Nrf2-dependent and independent pathways mediating pro-survival effects. In conclusion, by using some pharmacological tools as well as a reference compound, we dissected the role of the Nrf2-pathway in ARPE-19 stress response, suggesting that the Nrf2 induction represents an efficient defensive strategy to prevent the stress-induced damage.openCatanzaro M.; Lanni C.; Basagni F.; Rosini M.; Govoni S.; Amadio M.Catanzaro M.; Lanni C.; Basagni F.; Rosini M.; Govoni S.; Amadio M

A macroscopic model for pedestrian flows in panic situations

International audienceIn this paper we present the macroscopic model for pedestrian flows proposed by Colombo and Rosini [10] and show its main properties. In particular, this model is able to properly describe the movements of crowds, even after panic has arisen. Furthermore, it is able to reproduce the so called Braess' paradox for pedestrians. From the mathematical point of view, it provides one of the few examples of non classical shocks motivated by real problems, for which a global existence result is available. Finally, its assumptions were experimentally confirmed by an empirical study of a crowd crush on the Jamarat Bridge in Mina, Saudi Arabia, near Mecca, see [17]

Antibacterial Properties of D-Amino Acid Oxidase: Impact on the Food Industry

Food quality is also related to safety and prevention of spoilage. Biological antimicrobial agents represent suitable alternatives to clinical preservatives in food industry to increase both safety and stability of aliments. Here, we focused on the enzyme D-amino acid oxidase (DAAO) from the yeast Rhodotorula gracilis, a well-studied protein for biotechnological use based on its stability, high activity, and easy recombinant production. DAAO catalyzes the O-2-dependent oxidative deamination of D-enantiomer of amino acids generating alpha -keto acids, ammonia, and hydrogen peroxide. DAAO shows antibacterial activity on both Gram-positive and Gram-negative bacteria in the presence of D-alanine when tested on plates and reduced by half their growth when tested on liquid cultures. Control experiments performed with alternative amino acid-specific flavoenzymes (able or not to generate H2O2 acting on amino acids), a DAAO inactive variant, catalase (H2O2 scavenger), and L-amino acids instead of D-alanine identified H2O2 as the antibacterial agent. DAAO showed a good ability to decrease the bacterial growth on various food stuffs: e.g., 10-fold less colonies were formed on grated cheese incubated for 16 h at 37 degrees C when a tiny amount (0.01 mg corresponding to 1.2 units) of DAAO was added. No exogenous D-amino acids were added since DAAO used the ones naturally occurring or the ones generated during ripening. Notably, simultaneously to H2O2 generation, DAAO also acts as O-2-scavenger thus further hampering food deterioration