A model for enhanced and selective transport through biological membranes with alternating pores

We investigate the outflux of ions through the channels in a cell membrane. The channels undergo an open/close cycle according to a periodic schedule. Our study is based both on theoretical considerations relying on homogenization theory, and on Monte Carlo numerical simulations. We examine the onset of a limiting boundary behavior characterized by a constant ratio between the outflux and the local density, in the thermodynamics limit. The focus here is on the issue of selectivity, that is on the different behavior of the ion currents through the channel in the cases of the selected and non-selected species.Comment: arXiv admin note: text overlap with arXiv:1307.418

Antibacterial Activity of Dipeptide Constructions of Acetylsalicylic Acid and Nicotinic Acid

Two dipeptide drugs are synthesized utilizing an acetylsalicylic acid or nicotinic acid molecule for the framework. A D-alanine-D-alanine dipeptide moiety is attached to the carbonyl carbon of acetylsalicylic acid (I) and nicotinic acid (II). Dipeptide derivatives (I) and (II) showed significant reduction of Escherichia coli (E. coli) bacterial growth and colony-forming units. A mixture of (I) and (II) induced growth inhibition of 8%, 17.5%, 28%, and 42.5% at concentrations of 100, 200, 300, and 400 μg/mL, respectively. Ampicillin demonstrated much less growth inhibition of this penicillin-resistant E. coli bacteria. Derivatives (I) and (II) showed significant reduction of colony-forming units at concentrations higher than 200 μg/mL, whereas ampicillin showed no significant affect on colony-forming units. Both (I) and (II) produced no violations of the Rule of 5, indicating favorable characteristics for bioavailability. Molecular properties were determined and showed (I) to have a Log Kow of −0.22 with aqueous solubility of 683.8 mg/L, whereas (II) had a Log Kow of −1.00 and aqueous solubility of 6859 mg/L. A mixture of the parent compounds acetyl salicylic acid and nicotinic acid demonstrated some antibacterial activity

Relaxation Height in Energy Landscapes: an Application to Multiple Metastable States

The study of systems with multiple (not necessarily degenerate) metastable states presents subtle difficulties from the mathematical point of view related to the variational problem that has to be solved in these cases. We introduce the notion of relaxation height in a general energy landscape and we prove sufficient conditions which are valid even in presence of multiple metastable states. We show how these results can be used to approach the problem of multiple metastable states via the use of the modern theories of metastability. We finally apply these general results to the Blume--Capel model for a particular choice of the parameters ensuring the existence of two multiple, and not degenerate in energy, metastable states

Jobs and Competitiveness in a Polarised Europe

In the aftermath of the crisis, Europe is becoming more polarised in terms of employment, competitiveness and industrial specialisation. A “German-centred core”–which maintained employment and production–has emerged, contrasted by a “Southern periphery”, where major economic losses have occurred. Such geographical divergence is associated with a further polarisation in terms of skills. A new European industrial policy is needed to reverse this polarisation process and its dangerous implications for trade balances and cohesion

Novel Tuberculostatic Agents Suitable for Treatment of Mycobacterium tuberculosis Infections of the Central Nervous System

Aims: To demonstrate the efficacy of five small molecule compounds for inhibiting the growth of Mycobacterium tuberculosis. To present evidence that these compounds will penetrate into the central nervous system. Study Design: Five small molecule compounds bearing a hydrazide group were synthesized utilizing microwave excitation. These compounds were then placed into tissue culture with Mycobacterium tuberculosis at various concentrations for evaluation of bacterial growth inhibition. Place and Duration of Study: The compounds to be tested were prepared at the University of Nebraska Chemistry Department August 2013. The evaluation of antibacterial activity was determined at the Texas A&M Health Science Center during October to December of 2013. Methodology: Applying microwave excitation for generation of hydrazide groups within the structure of small molecule carboxylic acids, five agents were prepared for evaluation of bacterial growth inhibition. These agents were dissolved into tissue culture media at various concentrations. Having various levels of tuberculostatic agents, then tuberculosis bacteria were added to determine level of growth inhibition. Growth inhibition of the bacteria was achieved and measured by compound concentration for comparison and evaluation. Results: Five compounds having a hydrazide functional group greatly inhibited the growth of Mycobacterium tuberculosis. All five agents had molecular weight less than 215 grams/mole and polar surface area of less than 70 Angstroms2. Values of Log P ranged from -0.226 to 0.998. Values of Log BB (Log [Cbrain/Cblood]) ranged from -0.711 to - 0.525, with a range in central nervous system penetration Cbrain/Cblood of 0.195 to 0.299. All compounds showed zero violations of the Rule of 5. Substantial inhibition of bacterial growth was observed at concentrations as low as 30 micrograms/mL, as measured by optical density and colony forming units. Conclusion: These five hydrazide compounds substantially decreased the proliferation of tuberculosis bacteria at concentrations as low as 30 micrograms/mL. In addition, their physicochemical properties are shown to allow high levels of penetration into the central nervous system

The Mycobacterium marinum mel2 locus displays similarity to bacterial bioluminescence systems and plays a role in defense against reactive oxygen and nitrogen species

BACKGROUND: Mycobacteria have developed a number of pathways that provide partial protection against both reactive oxygen species (ROS) and reactive nitrogen species (RNS). We recently identified a locus in Mycobacterium marinum, mel2, that plays a role during infection of macrophages. The molecular mechanism of mel2 action is not well understood. RESULTS: To better understand the role of the M. marinum mel2 locus, we examined these genes for conserved motifs in silico. Striking similarities were observed between the mel2 locus and loci that encode bioluminescence in other bacterial species. Since bioluminescence systems can play a role in resistance to oxidative stress, we postulated that the mel2 locus might be important for mycobacterial resistance to ROS and RNS. We found that an M. marinum mutant in the first gene in this putative operon, melF, confers increased susceptibility to both ROS and RNS. This mutant is more susceptible to ROS and RNS together than either reactive species alone. CONCLUSION: These observations support a role for the M. marinum mel2 locus in resistance to oxidative stress and provide additional evidence that bioluminescence systems may have evolved from oxidative defense mechanisms

A phenomenological model of a downdraft biomass gasifier flexible to the feedstock composition and the reactor design

The development of a one-dimensional (1D) phenomenological model for biomass gasification in downdraft reactors is presented in this study; the model was developed with the aim of highlighting the main advantages and limits related to feedstocks that are different from woodchip, such as hydro-char derived from the hydrothermal carbonization of green waste, or a mix of olive pomace and sawdust. An experimental validation of the model is performed. The numerically evaluated temperature evolution along the reactor gasifier is found to be in agreement with locally measured values for all the considered biomasses. The model captures the pressure drop along the reactor axis, despite an underestimation with respect to the performed measurements. The producer gas composition resulting from the numerical model at the exit section is in quite good agreement with gas-chromatograph analyses (12% maximum error for CO and CO2 species), although the model predicts lower methane and hydrogen content in the syngas than the measurements show. Parametric analyses highlight that lower degrees of porosity enhance the pressure drop along the reactor axis, moving the zones characterized by the occurrence of the combustion and gasification phases towards the bottom. An increase in the biomass moisture content is associated with a delayed evolution of the temperature profile. The high energy expenditure in the evaporation phase occurs at the expense of the produced hydrogen and methane in the subsequent phases