A mesoscopic stochastic model for the specific consumption rate in substrate-limited microbial growth

The specific consumption rate of substrate, as well as the associated specific growth rate, is an essential parameter in the mathematical description of substrate-limited microbial growth. In this paper we develop a completely new kinetic model of substrate transport, based on recent knowledge on the structural biology of transport proteins, which correctly describes very accurate experimental results at near-zero substrate concentration values found in the literature, where the widespread Michaelis-Menten model fails. Additionally, our model converges asymptotically to Michaelis-Menten predictions as substrate concentration increases. Instead of the single active site enzymatic reaction of Michaelis-Menten type, the proposed model assumes a multi-site kinetics, simplified as an apparent all-or-none mechanism for the transport, which is controlled by means of the local substrate concentration in the close vicinity of the transport protein. Besides, the model also assumes that this local concentration is not equal to the mean substrate concentration experimentally determined in the culture medium. Instead, we propose that it fluctuates with a mostly exponential distribution of Weibull type

Grain Sorting Effects on Geochemical Characteristics of Sulfide Mine Tailings: a Case Study

The geochemical evolution of a sulfide mine tailings impoundment in SW Spain was studied. The impoundment was selected because of its small size and its tailings deposition system with a simple discharge point. The objective of this study was to test the hypothesis that mineral segregation associated to hydraulic sorting has significant effects on the geochemical characteristics and the long term weathering. Tailings samples were collected along depth profiles in three sampling points (proximal, central and distal to the point of discharge), and characterized by color, grain size, pH, acid-base account and chemical elements concentration, with the help of routine XRD analysis. Three vertical zones were identified: an upper oxidized zone, a transition intermediate zone, and an unoxidized zone. The analytical results indicate a segregation pattern in the unoxidized tailings based on differences in size and density of tailings grains. Near the discharge point, tailings were coarser and rich in pyrite, whereas the proportion of silicates increased from proximal to distal points. This results in a clear zoning which has consequences on geochemical and mineralogical evolution under weathering, showing substantial differences in the depth of the oxidation front, the acid generation and neutralization capacity, the formation of Fe secondary phases (jarosite) and the total content of the sulfide-related elements (Fe, As, Zn, Cu, Pb and Cd). The results of the study can serve to improve the theoretical bases for the development of conceptual models for predicting environmental impacts associated with sulfide tailings impoundments. Recently, the impoundment has been covered with a soil cover. This fact offers the possibility of new research on its evolution under new conditions

A pharmacogenetic intervention for the improvement of the safety profile of antipsychotic treatments

Antipsychotic drugs fail to achieve adequate response in 30–50% of treated patients and about 50% of them develop severe and lasting side effects. Treatment failure results in poorer prognosis with devastating repercussions for the patients, carers and broader society. Our study evaluated the clinical benefits of a pharmacogenetic intervention for the personalisation of antipsychotic treatment. Pharmacogenetic information in key CYP polymorphisms was used to adjust clinical doses in a group of patients who started or switched treatment with antipsychotic drugs (PharmG+, N = 123), and their results were compared with those of a group of patients treated following existing clinical guides (PharmG−, N = 167). There was no evidence of significant differences in side effects between the two arms. Although patients who had their antipsychotic dose adjusted according to CYPs polymorphisms (PharmG+) had a bigger reduction in side effects than those treated as usual (PharmG−), the difference was not statistically significant (p > 0.05 for all comparisons). However, PharmG+ patients treated with CYP2D6 substrates that were carriers of CYP2D6 UMs or PMs variants showed a significantly higher improvement in global, psychic and other UKU side effects than PharmG− patients (p = 0.02, p = 0.05 and p = 0.01, respectively). PharmG+ clozapine treated patients with CYP1A2 or CYP2C19 UM and PMs variants also showed higher reductions in UKU scores than PharmG− clozapine patients in general. However, those differences were not statistically significant. Pharmacogenetic interventions may improve the safety of antipsychotic treatments by reducing associated side effects. This intervention may be particularly useful when considering treatment with antipsychotics with one major metabolic pathway, and therefore more susceptible to be affected by functional variants of CYP enzymes.This research was funded by grants from the Institute Carlos III (FIS PI11/02006; FIS PI16/01029). A.G.-R. was partially funded by a private grant from the Jové family. Genotyping was partially conducted by the CEGEN-PRB2-ISCIII node, which is supported by grant PT13/001, ISCIIISGEFI/ FEDER

Obesity dependent metabolic signatures associated with nonalcoholic fatty liver disease progression

Our understanding of the mechanisms by which nonalcoholic fatty liver disease (NAFLD) progresses from simple steatosis to steatohepatitis (NASH) is still very limited. Despite the growing number of studies linking the disease with altered serum metabolite levels, an obstacle to the development of metabolome-based NAFLD predictors has been the lack of large cohort data from biopsy-proven patients matched for key metabolic features such as obesity. We studied 467 biopsied individuals with normal liver histology (n=90) or diagnosed with NAFLD (steatosis, n=246; NASH, n=131), randomly divided into estimation (80% of all patients) and validation (20% of all patients) groups. Qualitative determinations of 540 serum metabolite variables were performed using ultra-performance liquid chromatography coupled to mass spectrometry (UPLCMS). The metabolic profile was dependent on patient body-mass index (BMI), suggesting that the NAFLD pathogenesis mechanism may be quite different depending on an individual’s level of obesity. A BMI-stratified multivariate model based on the NAFLD serum metabolic profile was used to separate patients with and without NASH. The area under the receiver operating characteristic curve was 0.87 in the estimation and 0.85 in the validation group. The cutoff (0.54) corresponding to maximum average diagnostic accuracy (0.82) predicted NASH with a sensitivity of 0.71 and a specificity of 0.92 (negative/positive predictive values = 0.82/0.84). The present data, indicating that a BMI-dependent serum metabolic profile may be able to reliably distinguish NASH from steatosis patients, have significant implications for the development of NASH biomarkers and potential novel targets for therapeutic intervention

Maximum population transfer in a periodically driven two-level system

We study the dynamics of a two-level quantum system under the influence of sinusoidal driving in the intermediate frequency regime. Analyzing the Floquet quasienergy spectrum, we find combinations of the field parameters for which population transfer is optimal and takes place through a series of well defined steps of fixed duration. We also show how the corresponding evolution operator can be approximated at all times by a very simple analytical expression. We propose this model as being specially suitable for treating periodic driving at avoided crossings found in complex multi-level systems, and thus show a relevant application of our results to designing a control protocol in a realistic molecular modelComment: 7 pages, 6 figure

The Poincare-Birkhoff theorem in Quantum Mechanics

Quantum manifestations of the dynamics around resonant tori in perturbed Hamiltonian systems, dictated by the Poincar\'e--Birkhoff theorem, are shown to exist. They are embedded in the interactions involving states which differ in a number of quanta equal to the order of the classical resonance. Moreover, the associated classical phase space structures are mimicked in the quasiprobability density functions and their zeros.Comment: 5 pages, 3 figures, Full resolution figures available at http://www.df.uba.ar/users/wisniaki/publications.htm

Correspondence between classical and quantum resonances

Bifurcations take place in molecular Hamiltonian nonlinear systems as the excitation energy increases, leading to the appearance of different classical resonances. In this paper, we study the quantum manifestations of these classical resonances in the isomerizing system CN-Li Li-CN. By using a correlation diagram of eigenenergies versus Planck constant, we show the existence of different series of avoided crossings, leading to the corresponding series of quantum resonances, which represent the quantum manifestations of the classical resonances. Moreover, the extrapolation of these series to h = 0 unveils the correspondence between the bifurcation energy of classical resonances and the energy of the series of quantum resonances in the semiclassical limit → 0. Additionally, in order to obtain analytical expressions for our results, a semiclassical theory is develope

A 0535+26: an X-ray/Optical Tour

We compiled X-ray and Optical observations of the accreting X-ray binary system A 0535+262 since its discovery in 1975, that will allow us to shed light on the unpredictable behavior of this binary system. We present the data in terms of the Be-disk interaction with the neutron star companion. In addition, we show recent results from the continuous monitoring of this source by the Gamma-ray Burst Monitor(GBM), on board the Fermi observatory, since its launch in 2008 June 11.Comment: 4 pages, 5 figures, Conference proceeding of "Astrophysics of Neutron Stars 2010 - a conference in honor of M. Ali Alpar", 2-6 August 2010, Cesme, Izmir, Turke

Crowdsourcing malaria parasite quantification: an online game for analyzing images of infected thick blood smears

Background: There are 600,000 new malaria cases daily worldwide. The gold standard for estimating the parasite burden and the corresponding severity of the disease consists in manually counting the number of parasites in blood smears through a microscope, a process that can take more than 20 minutes of an expert microscopist’s time. Objective: This research tests the feasibility of a crowdsourced approach to malaria image analysis. In particular, we investigated whether anonymous volunteers with no prior experience would be able to count malaria parasites in digitized images of thick blood smears by playing a Web-based game. Methods: The experimental system consisted of a Web-based game where online volunteers were tasked with detecting parasites in digitized blood sample images coupled with a decision algorithm that combined the analyses from several players to produce an improved collective detection outcome. Data were collected through the MalariaSpot website. Random images of thick blood films containing Plasmodium falciparum at medium to low parasitemias, acquired by conventional optical microscopy, were presented to players. In the game, players had to find and tag as many parasites as possible in 1 minute. In the event that players found all the parasites present in the image, they were presented with a new image. In order to combine the choices of different players into a single crowd decision, we implemented an image processing pipeline and a quorum algorithm that judged a parasite tagged when a group of players agreed on its position. Results: Over 1 month, anonymous players from 95 countries played more than 12,000 games and generated a database of more than 270,000 clicks on the test images. Results revealed that combining 22 games from nonexpert players achieved a parasite counting accuracy higher than 99%. This performance could be obtained also by combining 13 games from players trained for 1 minute. Exhaustive computations measured the parasite counting accuracy for all players as a function of the number of games considered and the experience of the players. In addition, we propose a mathematical equation that accurately models the collective parasite counting performance. Conclusions: This research validates the online gaming approach for crowdsourced counting of malaria parasites in images of thick blood films. The findings support the conclusion that nonexperts are able to rapidly learn how to identify the typical features of malaria parasites in digitized thick blood samples and that combining the analyses of several users provides similar parasite counting accuracy rates as those of expert microscopists. This experiment illustrates the potential of the crowdsourced gaming approach for performing routine malaria parasite quantification, and more generally for solving biomedical image analysis problems, with future potential for telediagnosis related to global health challenges