Just add sugar for carbohydrate induced self-assembly of curcumin.

In nature, self-assembly processes based on amphiphilic molecules play an integral part in the design of structures of higher order such as cells. Among them, amphiphilic glycoproteins or glycolipids take on a pivotal role due to their bioactivity. Here we show that sugars, in particular, fructose, are capable of directing the self-assembly of highly insoluble curcumin resulting in the formation of well-defined capsules based on non-covalent forces. Simply by mixing an aqueous solution of fructose and curcumin in an open vessel leads to the generation of capsules with sizes ranging between 100 and 150 nm independent of the initial concentrations used. Our results demonstrate that hydrogen bonding displayed by fructose can induce the self-assembly of hydrophobic molecules such as curcumin into well-ordered structures, and serving as a simple and virtually instantaneous way of making nanoparticles from curcumin in water with the potential for template polymerization and nanocarriers.

Binding and Release between Polymeric Carrier and Protein Drug: pH-Mediated Interplay of Coulomb Forces, Hydrogen Bonding, van der Waals Interactions, and Entropy.

The accelerating search for new types of drugs and delivery strategies poses challenge to understanding the mechanism of delivery. To this end, a detailed atomistic picture of binding between the drug and carrier is quintessential. Although many studies focus on the electrostatics of drug-vector interactions, it has also been pointed out that entropic factors relating to water and counterions can play an important role. By carrying out extensive molecular dynamics simulations and subsequently validating with experiments, we shed light herein on the binding in aqueous solution between a protein drug and polymeric carrier. We examined the complexation between the polymer poly(ethylene glycol) methyl ether acrylate-b-poly(carboxyethyl acrylate (PEGMEA-b-PCEA) and the protein egg white lysozyme, a system that acts as a model for polymer-vector/protein-drug delivery systems. The complexation has been visualized and characterized using contact maps and hydrogen bonding analyses for five independent simulations of the complex, each running over 100 ns. Binding at physiological pH is, as expected, mediated by Coulombic attraction between the positively charged protein and negatively charged carboxylate groups on the polymer. However, we find that consideration of electrostatics alone is insufficient to explain the complexation behavior at low pH. Intracomplex hydrogen bonds, van der Waals interactions, as well as water-water interactions dictate that the polymer does not release the protein at pH 4.8 or indeed at pH 3.2 even though the Coulombic attractions are largely removed as carboxylate groups on the polymer become titrated. Experiments in aqueous solution carried out at pH 7.0, 4.5, and 3.0 confirm the veracity of the computed binding behavior. Overall, these combined simulation and experimental results illustrate that coulomb interactions need to be complemented with consideration of other entropic forces, mediated by van der Waals interactions and hydrogen bonding, to search for adequate descriptors to predict binding and release properties of polymer-protein complexes. Advances in computational power over the past decade make atomistic molecular dynamics simulations such as implemented here one of the few avenues currently available to elucidate the complexity of these interactions and provide insights toward finding adequate descriptors. Thus, there remains much room for improvement of design principles for efficient capture and release delivery systems.

Dynamical Interactions of 5-Fluorouracil Drug with Dendritic Peptide Vectors: The Impact of Dendrimer Generation, Charge, Counterions, and Structured Water.

Molecular dynamics simulations are utilized to investigate the interactions between the skin cancer drug 5-fluorouracil (5FU) and peptide-based dendritic carrier systems. We find that these drug-carrier interactions do not conform to the traditional picture of long-time retention of the drug within a hydrophobic core of the dendrimer carrier. Rather, 5FU, which is moderately soluble in its own right, experiences weak, transient chattering interactions all over the dendrimer, mediated through multiple short-lived hydrogen bonding and close contact events. We find that charge on the periphery of the dendrimer actually has a negative effect on the frequency of drug-carrier interactions due to a counterion screening effect that has not previously been observed. However, charge is nevertheless an important feature since neutral dendrimers are shown to have a significant mutual attraction that can lead to clustering or agglomeration. This clustering is prevented due to charge repulsion for the titrated dendrimers, such that they remain independent in solution.

Effects of Confinement on the Dielectric Response of Water Extends up to Mesoscale Dimensions.

The extent of confinement effects on water is not clear in the literature. While some properties are affected only within a few nanometers from the wall surface, others are affected over long length scales, but the range is not clear. In this work, we have examined the dielectric response of confined water under the influence of external electric fields along with the dipolar fluctuations at equilibrium. The confinement induces a strong anisotropic effect which is evident up to 100 nm channel width, and may extend to macroscopic dimensions. The root-mean-square fluctuations of the total orientational dipole moment in the direction perpendicular to the surfaces is 1 order of magnitude smaller than the value attained in the parallel direction and is independent of the channel width. Consequently, the isotropic condition is unlikely to be recovered until the channel width reaches macroscopic dimensions. Consistent with dipole moment fluctuations, the effect of confinement on the dielectric response also persists up to channel widths considerably beyond 100 nm. When an electric field is applied in the perpendicular direction, the orientational relaxation is 3 orders of magnitude faster than the dipolar relaxation in the parallel direction and independent of temperature.

Molecular dynamics study of nanoconfined water flow driven by rotating electric fields under realistic experimental conditions.

In our recent work, J. Chem. Phys. 2013, 138, 154712, we demonstrated the feasibility of unidirectional pumping of water, exploiting translational-rotational momentum coupling using nonequilibrium molecular dynamics simulations. Flow can be sustained when the fluid is driven out of equilibrium by an external spatially uniform rotating electric field and confined between two planar surfaces exposing different degrees of hydrophobicity. The permanent dipole moment of water follows the rotating field, thus inducing the molecules to spin, and the torque exerted by the field is continuously injected into the fluid, enabling a steady conversion of spin angular momentum into linear momentum. The translational-rotational coupling is a sensitive function of the rotating electric field parameters. In this work, we have found that there exists a small energy dissipation region attainable when the frequency of the rotating electric field matches the inverse of the dielectric relaxation time of water and when its amplitude lies in a range just before dielectric saturation effects take place. In this region, that is, when the frequency lies in a small window of the microwave region around ∼20 GHz and amplitude ∼0.03 V Å(-1), the translational-rotational coupling is most effective, yielding fluid velocities of magnitudes of ∼2 ms(-1) with only moderate fluid heating. In this work, we also confine water to a realistic nanochannel made of graphene giving a hydrophobic surface on one side and ß-cristobalite giving a hydrophilic surface on the other, reproducing slip-and-stick velocity boundary conditions, respectively. This enables us to demonstrate that in a realistic environment, the coupling can be effectively exploited to achieve noncontact pumping of water at the nanoscale. A quantitative comparison between nonequilibrium molecular dynamics and analytical solutions of the extended Navier-Stokes equations, including an external rotating electric field has been performed, showing excellent agreement when the electric field parameters match the aforementioned small energy dissipation region.

A new and effective method for thermostatting confined fluids.

We present a simple thermostatting method suitable for nanoconfined fluid systems. Two conventional strategies involve thermostatting the fluid directly or employing a thermal wall that couples only the wall atoms with the thermostat. When only a thermal wall is implemented, the temperature control of the fluid is true to the actual experiment and the heat is transferred from the fluid to the walls. However, for large or complex systems it can often be computationally prohibitive to employ thermal walls. To overcome this limitation many researchers choose to freeze wall atoms and instead apply a synthetic thermostat to the fluid directly through the equations of motion. This, however, can have serious consequences for the mechanical, thermodynamic, and dynamical properties of the fluid by introducing unphysical behaviour into the system [Bernardi et al., J. Chem. Phys. 132, 244706 (2010)]. In this paper, we propose a simple scheme which enables working with both frozen walls and naturally thermostatted liquids. This is done by superimposing the walls with oscillating particles, which vibrate on the edge of the fluid control volume. These particles exchange energy with the fluid molecules, but do not interact with wall atoms or each other, thus behaving as virtual particles. Their displacements violate the Lindemann criterion for melting, in such a way that the net effect would not amount to an additional confining surface. One advantage over standard techniques is the reduced computational cost, particularly for large walls, since they can be kept rigid. Another advantage over accepted strategies is the opportunity to freeze complex charged walls such as ß-cristobalite. The method furthermore overcomes the problem with polar fluids such as water, as thermalized charged surfaces require higher spring constants to preserve structural stability, due to the effects of strong Coulomb interactions, thus inevitably degrading the thermostatting efficiency.

Electropumping of water with rotating electric fields.

Pumping of fluids confined to nanometer dimension spaces is a technically challenging yet vitally important technological application with far reaching consequences for lab-on-a-chip devices, biomimetic nanoscale reactors, nanoscale filtration devices and the like. All current pumping mechanisms require some sort of direct intrusion into the nanofluidic system, and involve mechanical or electronic components. In this paper, we present the first nonequilibrium molecular dynamics results to demonstrate that non-intrusive electropumping of liquid water on the nanoscale can be performed by subtly exploiting the coupling of spin angular momentum to linear streaming momentum. A spatially uniform rotating electric field is applied to water molecules, which couples to their permanent electric dipole moments. The resulting molecular rotational momentum is converted into linear streaming momentum of the fluid. By selectively tuning the degree of hydrophobicity of the solid walls one can generate a net unidirectional flow. Our results for the linear streaming and angular velocities of the confined water are in general agreement with the extended hydrodynamical theory for this process, though also suggest refinements to the theory are required. These numerical experiments confirm that this new concept for pumping of polar nanofluids can be employed under laboratory conditions, opening up significant new technological possibilities.

A novel non-protein-coding infection-specific gene family is clustered throughout the genome of Phytophthora infestans.

Phytophthora infestans is the cause of late blight, a devastating and re-emerging disease of potato. Significant advances have been made in understanding the biology of P. infestans, and in the development of molecular tools to study this oomycete. Nevertheless, little is known about the molecular bases of the establishment or development of disease in this hemibiotrophic pathogen. Suppression subtractive hybridization (SSH) was used to generate cDNA enriched for sequences upregulated during potato infection. To identify pathogen-derived cDNAs, and eliminate host sequences from further study, SSH cDNA was hybridized to a P. infestans bacterial artificial chromosome library. A new gene family was identified called Pinci1, comprising more than 400 members arranged in clusters of up to nine copies throughout the P. infestans draft genome sequence. Real-time RT-PCR was used to quantify the expression of five classes of transcript within the family, relative to the constitutively expressed PiactA gene, and it revealed them to be significantly upregulated from 12 to 33 h post-inoculation, a period defining the biotrophic phase of infection. Computational analysis of sequences suggested that transcripts were non-protein coding, and this was confirmed by transient expression of FLAG-tagged ORFs in P. infestans.

Sodium ferrate (IV) and sodium hypochlorite in disinfection of biologically treated effluents. Ammonium nitrogen protection against THMs and HAAs.

The work described in this paper presents an evaluation of disinfection by-products generation in four different biological treatment plant effluents, making use of sodium hypochlorite and sodium ferrate (IV) at varying concentration and reaction time. Correlations between pH, chemical oxygen demand, total organic carbon, ammonium nitrogen, combined chlorine and trihalomethanes (THMs) and haloacetic acids (HAAs) were carried out. Disinfection by-products generation presented a direct relation with concentration and sodium hypochlorite reaction time. For the highest hypochlorite concentration employed (20 mg L(-1)) and highest reaction time (168 h), the THMs total did not exceed 312.96 microg L(-1), a value that lies below the Brazilian emission standard for treated effluents (1 mg L(-1) of chloroform). The THMs presented an inverse correlation with ammonium nitrogen, when inverse (R(2) = 0.646; P < 0.001) and exponential (R(2) = 0.707; P < 0.001) function were used. As per HAAs this same relation was observed for logarithmic (R(2) = 0.0397 P < 0.001) and exponential (R(2) = 0.508; P < 0.001) functions. The more nitrified the effluent, the bigger the chlorinated disinfection by-product generation. The disinfectant sodium ferrate (IV) does not lead to halogenated by-product formation.

Indice de impacto dos resíduos sólidos urbanos na saúde pública (IIRSP): metodologia e aplicação / Impact index of solid wastes management systems on public health (IIRSP): methodology and application

A redução do número de enfermidades produzidas, direta ou indiretamente, pelos resíduos sólidos depende de uma coleta eficiente e de uma adequada disposição final. Com as informações obtidas da aplicação de um questionário enviado aos municípios sul rio-grandenses divididos em sete regiões homogêneas, foram desenvolvidos indicadores e, por meio de procedimentos estatísticos não paramétricos, estruturados oito índices (índices específicos) que formaram um índice geral de controle de qualidade dos serviços de limpeza urbana. O artigo apresenta um sumário e um exemplo da metodologia utilizada para a criação do índice de Impacto dos Resíduos Sólidos Urbanos na Saúde Pública (IIRSP), o qual mais diretamente espelha a relação Resíduos sólidos-homem-saúde pública.