Colloidal analogs of molecular chain stoppers

A similarity between chemical reactions and self-assembly of nanoparticles offers a strategy that can enrich both the synthetic chemistry and the nanoscience fields. Synthetic methods should enable quantitative control of the structural characteristics of nanoparticle ensembles such as their aggregation number or directionality, whereas the capability to visualize and analyze emerging nanostructures using characterization tools can provide insight into intelligent molecular design and mechanisms of chemical reactions. We explored this twofold concept for an exemplary system including the polymerization of bifunctional nanoparticles in the presence of monofunctional colloidal chain stoppers. Using reaction-specific design rules, we synthesized chain stoppers with controlled reactivity and achieved quantitative fine-tuning of the self-assembled structures. Analysis of the nanostructures provided information about polymerization kinetics, side reactions, and the distribution of all of the species in the reaction system. A quantitative model was developed to account for the reactivity, kinetics, and side reactions of nanoparticles, all governed by the design of colloidal chain stoppers. This work provided the ability to test theoretical models developed for molecular polymerization.The similarity between chemical reactions and colloidal self-assembly forms a bridge between molecular and colloidal length scales, spanning over several orders of magnitude (1–3). It is currently well-established that a broad range of particles with two reactive patches, such as polymer microbeads (4), inorganic nanoparticles (5), and block copolymer micelles (6), act similar to bifunctional molecular monomers and organize themselves into one-dimensional polymer-like structures. The self-assembly of colloidal polymers can also be assisted by the application of an electric (7) or magnetic field (8). The analogy between chemical reactions and the self-assembly process offers a mutually beneficial approach: (i) the use of synthetic concepts as a strategy for controllable and quantitative self-assembly of colloidal particles into structures with well-defined sizes, spatial organization, and directionality and (ii) the development of fundamental knowledge about chemical reactions by visualizing colloidal assemblies.The replication of synthetic concepts developed at the molecular scale––beyond qualitative prediction of a particular structure––should benefit the self-assembly of colloidal polymers built from nanoparticles. Collective plasmonic, excitonic, and magnetic properties of nanoparticle chains depend on their degree of polymerization (9–11). Nanoparticle chains have potential applications as sensors (12), nanoantennas (13), or waveguides (14), to name just a few applications, and their successful realization relies on the ability to precisely control nanopolymer structure. Recently, we reported the ability to predict the average degree of polymerization $\bar{X}$_n of nanoparticle chains for a particular self-assembly time (5); however, without quenching the self-assembly after an appropriate time, the desired final value of $\bar{X}$_n cannot be achieved. Synthetic polymer chemistry offers an elegant way to tune $\bar{X}$_n by changing the stoichiometry of reacting molecules. For monomers with two functional groups A and B, the value of $\bar{X}$_n is controlled by adding to the reaction system a small amount of monofunctional molecules that are called chain stoppers (CSs) (15). In the course of polymerization, a CS attaches to the polymer end and makes it incapable of further reaction. The value of $\bar{X}$_n of the polymer is tuned by varying the amount of CSs introduced in the reaction system. This efficient approach has not been explored for controlling the degree of polymerization (or the length) of colloidal polymers.Importantly, the ability to visualize individual nanoparticles and their ensembles, and analyze their distribution in the system brings a unique capability to take snapshots of different stages of colloidal polymerization reactions and in this manner, test theoretical models developed for synthetic polymer chemistry. For example, supramolecular polymerization uses bifunctional monomers and CSs with identical, self-complementary functional groups (16). Control of $\bar{X}$_n of supramolecular polymers has been developed under the assumption of equal reactivities and strengths of CS–CS, CS–monomer, and monomer–monomer interactions (16–18). Side reactions of CSs such as their dimerization and binding to the junctions between the repeat units of the polymer have been neglected. Direct characterization of supramolecular polymers is not trivial due to their dynamic nature, and conventional polymer characterization techniques, e.g., gel permission chromatography, may require dilution of polymer solutions or the use of elevated temperatures, which can change polymer properties (16). Visualization of nanoparticle chains by electron microscopy in the course of the polymerization process enables the validation of the assumptions made for CS reactions and, overall, provides insight into the intrinsic details of supramolecular polymerization, although nanopolymer chains are generally characterized by a lower value of $\bar{X}$_n than their molecular counterparts. Furthermore, nanoscience-specific techniques such as the measurements of time-dependent red shift of surface plasmon resonances of metal nanoparticles can be used to characterize their polymerization in linear chains. Importantly, the design rules established for efficient colloidal CSs can be extended to the synthesis of their molecular analogs to control reaction kinetics and the distribution of molecular species in the reaction system.The present work highlights mutual enrichment of nanoparticle self-assembly and polymerization reactions. We designed colloidal analogs of molecular CSs with a particular geometry and surface properties to achieve control of their reactivity, minimize the effect of the side reactions of CSs, and fine-tune the value of $\bar{X}$_n of polymers formed from bifunctional gold nanorods (NRs). We proposed a quantitative model that––based on the reaction kinetics––quantitatively predicts the value of $\bar{X}$_n and the relative concentrations of all of the species in the reaction system, all controlled by the intelligent design of CSs. These results provide an important contribution to supramolecular polymerization.     

Risedronate Gastrointestinal Absorption Is Independent of Site and Rate of Administration

Purpose. Two studies were conducted to compare the absorption of risedronate administered as a solution to three different gastrointestinal sites (study A) and to determine the extent of absorption of risedronate solution administered by rapid and slow infusion to the second part of the duodenum (study B). Methods. Each study was designed as a single-dose, crossover (three periods, study A; two periods, study B) trial in healthy male subjects, with a 14-day washout period between dosing. Subjects fasted overnight before drug administration and for 4 hours after drug administration. In study A, a risedronate solution of 40 mg in 30 mL of water was administered directly into the stomach, the second part of the duodenum, or the terminal ileum over 1 minute via a nasoenteral tube in a three-period crossover design. In study B, a risedronate solution of 40 mg in 30 mL of water was administered directly into the second part of the duodenum over 1 minute and over 1 hour in a randomized, two-period crossover design. Serum and urine samples were obtained for 48 hours after dosing for risedronate analysis. Results. Eight subjects completed each study. No statistically significant site-specific differences in any pharmacokinetic parameter were observed (study A). Based on the area under the serum concentration-time profile and the amount of drug excreted in the urine unchanged, the extent of risedronate absorption did not differ significantly following a rapid or a slow infusion (study B). Only minor symptomatic complaints were reported by subjects, such as headaches and body aches. Conclusions. These studies indicate that the rate and extent of risedronate absorption are independent of the site of administration along the gastrointestinal tract, and that the extent of absorption is not affected by the rate of administration.     

Effectiveness of cleaning practices in removing pesticides from home environments

The deposition of agricultural pesticides in the homes of agricultural workers and residents of agricultural communities is a major environmental health concern. The effectiveness of home cleaning activities in removing pesticides from home surfaces has not been tested. An intervention study was conducted to assess the effectiveness of cleaning windowsills, floors and carpets in a sample of 10 farmworker homes. Baseline measures of organophosphorus (OP) pesticide residues were obtained, a standardized cleaning intervention was applied and follow-up measures of pesticide residues were obtained within 24-48 hours after the cleaning and 12 months later. House dust was analyzed for six OP pesticides. All homes had detectable baseline levels of OP pesticides on floors and windowsills. Cleaning of linoleum floors was ineffective in removing total pesticide residues and cleaning effectiveness varied among the pesticides. The cleaning of total OP pesticides on the windowsills was effective (median decrease was 0.0029 microg/cm(2), 1-sided p-value = 0.01). Steam cleaning carpets essentially reduced the amounts to non-detectable levels. In 12 months the levels in carpets had accumulated to one-third of the baseline levels. These results provide evidence that cleaning practices can reduce the amount of pesticides in agricultural homes; however the type of surface being cleaned and the pesticides present in the home may influence results.     

Extracorporeal shockwave therapy for Peyronie＇s disease： an alternative treatment？

Aim： To determine retrospectively the safety and efficacy of extracorporeal shock wave therapy （ESWT） in patients with Peyronie＇s disease. Methods： Fifty-three patients with stable Peyronie＇s disease underwent ESWT （group 1）. Fifteen patients matched with the baseline characteristic of the patients in group 1, who received no treatment, were used as the control （group 2）. The patients＇ erectile function （International Index of Erectile Function [IIEF-5] score）, pain severity （visual analog scale）, plaque size and degree of penile angulation were assessed before and after the treatment in group 1 and during the follow-up in group 2. Results： The mean follow-up time was 32 months （range： 6-64 months） in group 1 and 35 months （range： 9-48 months） in group 2. All the patients were available for the follow-up. Considering erectile function and plaque size, no significant changes （P 〉 0.05） were observed in group 1 before or after the ESWT. A total of 39 patients （74%） reported a significant effect in pain relief in group 1 after ESWT. However, regarding improvement in pain, IIEF-5 score and plaque size, no significant differences were observed between the two groups. In 21 patients （40%） of group 1, the deviation angle was decreased more than 10° with a mean reduction in all patients of 11° （range： 6-20°）. No serious complications were noted considering ESWT procedure. Conclusion： ESWT is a minimally invasive and safe alternative procedure for the treatment of Peyronie＇s disease. However, the effect of ESWT on penile pain, sexual function and plaque size remains questionable.     

Differential relationships between sub-traits of BIS-11 impulsivity and executive processes: An ERP study

There is mixed evidence for a relationship between impulsivity and executive functions. Although impulsivity is heterogeneous, previous research did not examine partial relationships controlling for shared variance across sub-traits to evaluate the specificity of these associations. Eighty-five undergraduates completed the Barratt Impulsiveness Scale-11 (BIS-11) and the AX-expectancy version of the Continuous Performance Task (AX-CPT). This task engenders a conflict between two response tendencies by manipulating the frequency of specific trial types. We conducted mixed model analyses to determine the unique variance in behavioral and electrophysiological indices of relevant cognitive functions accounted for by the facets of BIS-11. Motor Impulsiveness was associated with smaller P3 across sites and conditions suggesting a general cognitive limitation not specific to the condition requiring the most inhibition, and larger N2 in some conditions indicating heightened conflict detection. Non-Planning Impulsiveness was related to smaller N2 when inhibiting a primed response and with greater P3 in some contexts. Attentional Impulsiveness appeared to be associated with an inefficient conflict detection system indicated by relatively normal engagement in trials involving the non-potent response, but relatively over engagement in the prepotent condition. Our findings suggest that sub-traits of impulsivity are differentially related to executive processes.