Synthesis and characterization of biodegradable lignin nanoparticles with tunable surface properties

Lignin nanoparticles can serve as biodegradable carriers of biocidal actives with minimal environmental footprint. Here we describe the colloidal synthesis and interfacial design of nanoparticles with tunable surface properties using two different lignin precursors, Kraft (Indulin AT) lignin and Organosolv (high-purity lignin). The green synthesis process is based on flash precipitation of dissolved lignin polymer, which enabled the formation of nanoparticles in the size range of 45–250 nm. The size evolution of the two types of lignin particles is fitted on the basis of modified diffusive growth kinetics and mass balance dependencies. The surface properties of the nanoparticles are fine-tuned by coating them with a cationic polyelectrolyte, poly(diallyldimethylammonium chloride). We analyze how the colloidal stability and dispersion properties of these two types of nanoparticles vary as a function of pH and salinities. The data show that the properties of the nanoparticles are governed by the type of lignin used and the presence of polyelectrolyte surface coating. The coating allows the control of the nanoparticles’ surface charge and the extension of their stability into strongly basic regimes, facilitating their potential application at extreme pH conditions

6'-Methoxy Raloxifene-analog enhances mouse bone properties with reduced estrogen receptor binding

Raloxifene (RAL) is an FDA-approved drug used to treat osteoporosis in postmenopausal women. RAL suppresses bone loss primarily through its role as a selective estrogen receptor modulator (SERM). This hormonal estrogen therapy promotes unintended side effects, such as hot flashes and increased thrombosis risk, and prevents the drug from being used in some patient populations at-risk for fracture, including children with bone disorders. It has recently been demonstrated that RAL can have significant positive effects on overall bone mechanical properties by binding to collagen and increasing bone tissue hydration in a cell-independent manner. A Raloxifene-Analog (RAL-A) was synthesized by replacing the 6-hydroxyl substituent with 6-methoxy in effort to reduce the compound's binding affinity for estrogen receptors (ER) while maintaining its collagen-binding ability. It was hypothesized that RAL-A would improve the mechanical integrity of bone in a manner similar to RAL, but with reduced estrogen receptor binding. Molecular assessment showed that while RAL-A did reduce ER binding, downstream ER signaling was not completely abolished. In-vitro, RAL-A performed similarly to RAL and had an identical concentration threshold on osteocyte cell proliferation, differentiation, and function. To assess treatment effect in-vivo, wildtype (WT) and heterozygous (OIM+/-) female mice from the Osteogenesis Imperfecta (OI) murine model were treated with either RAL or RAL-A from 8 weeks to 16 weeks of age. There was an untreated control group for each genotype as well. Bone microarchitecture was assessed using microCT, and mechanical behavior was assessed using 3-point bending. Results indicate that both compounds produced analogous gains in tibial trabecular and cortical microarchitecture. While WT mechanical properties were not drastically altered with either treatment, OIM+/- mechanical properties were significantly enhanced, most notably, in post-yield properties including bone toughness. This proof-of-concept study shows promising results and warrants the exploration of additional analog iterations to further reduce ER binding and improve fracture resistance

Disease transmission models for public health decision making: analysis of epidemic and endemic conditions caused by waterborne pathogens.

Developing effective policy for environmental health issues requires integrating large collections of information that are diverse, highly variable, and uncertain. Despite these uncertainties in the science, decisions must be made. These decisions often have been based on risk assessment. We argue that two important features of risk assessment are to identify research needs and to provide information for decision making. One type of information that a model can provide is the sensitivity of making one decision over another on factors that drive public health risk. To achieve this goal, a risk assessment framework must be based on a description of the exposure and disease processes. Regarding exposure to waterborne pathogens, the appropriate framework is one that explicitly models the disease transmission pathways of pathogens. This approach provides a crucial link between science and policy. Two studies--a Giardia risk assessment case study and an analysis of the 1993 Milwaukee, Wisconsin, Cryptosporidium outbreak--illustrate the role that models can play in policy making

Correcting for serial dependence in studies of respiratory dynamics

Understanding the physiological impact of drug treatments on patients is important in assessing their performance and determining possible side effects. While this effect might be best determined in individual subjects, conventional methods assess treatment performance by averaging a physiological measure of interest before and after drug administration for n subjects. Summarizing large numbers of time-series observations in two means for each subject in this way results in significant information loss. Treatment effect can instead be analyzed in individual subjects. Because serial dependence of observations from the same animal must then be considered, methods that assume independence of observations, such as the t-test and z-test, cannot be used. We address this issue in the case of respiratory data collected from anesthetized rats that were injected with a dopamine agonist. In order to accurately assess treatment effect in time-series data, we begin by formulating a method of conditional likelihood maximization to estimate the parameters of a first-order autoregressive (AR) process. We show that treatment effect of a dopamine agonist can be determined while incorporating serial effect into the analysis. In addition, while maximum likelihood estimators of a large sample with independent observations may converge to an asymptotically normal distribution, this result of large sample theory may not hold when observations are serially dependent. In this case, a parametric bootstrap comparison can be used to approximate an appropriate measure of uncertainty.National Institutes of Health (U.S.) (Grant DP1-OD003646)National Institutes of Health (U.S.) (Grant K08-GM094394)National Institutes of Health (U.S.) (Grant K08-GM083216

Methylphenidate Actively Induces Emergence from General Anesthesia

Background: Although accumulating evidence suggests that arousal pathways in the brain play important roles in emergence from general anesthesia, the roles of monoaminergic arousal circuits are unclear. In this study, the authors tested the hypothesis that methylphenidate (an inhibitor of dopamine and norepinephrine transporters) induces emergence from isoflurane general anesthesia. Methods: Using adult rats, the authors tested the effect of intravenous methylphenidate on time to emergence from isoflurane general anesthesia. They then performed experiments to test separately for methylphenidate-induced changes in arousal and changes in minute ventilation. A dose–response study was performed to test for methylphenidate-induced restoration of righting during continuous isoflurane general anesthesia. Surface electroencephalogram recordings were performed to observe neurophysiological changes. Plethysmography recordings and arterial blood gas analysis were performed to assess methylphenidate-induced changes in respiratory function. Intravenous droperidol was administered to test for inhibition of methylphenidate's actions. Results: Methylphenidate decreased median time to emergence from 280 to 91 s. The median difference in time to emergence without methylphenidate compared with administration of methylphenidate was 200 [155–331] s (median, [95% CI]). During continuous inhalation of isoflurane, methylphenidate induced return of righting in a dose-dependent manner, induced a shift in electroencephalogram power from delta (less than 4 Hz) to theta (4–8 Hz), and induced an increase in minute ventilation. Administration of intravenous droperidol (0.5 mg/kg) before intravenous methylphenidate (5 mg/kg) largely inhibited methylphenidate-induced emergence behavior, electroencephalogram changes, and changes in minute ventilation. Conclusions: Methylphenidate actively induces emergence from isoflurane general anesthesia by increasing arousal and respiratory drive, possibly through activation of dopaminergic and adrenergic arousal circuits. The authors' findings suggest that methylphenidate may be useful clinically as an agent to reverse general anesthetic-induced unconsciousness and respiratory depression at the end of surgery.National Institutes of Health (U.S.) (Grant DP1-OD003646)National Institutes of Health (U.S.) (Grant K08-GM094394)National Institutes of Health (U.S.) (Grant K08-GM083216)Massachusetts General Hospital. Dept. of Anesthesia and Critical Car

Implications of Pseudospin Symmetry on Relativistic Magnetic Properties and Gamow - Teller Transitions in Nuclei

Recently it has been shown that pseudospin symmetry has its origins in a relativistic symmetry of the Dirac Hamiltonian. Using this symmetry we relate single - nucleon relativistic magnetic moments of states in a pseudospin doublet to the relativistic magnetic dipole transitions between the states in the doublet, and we relate single - nucleon relativistic Gamow - Teller transitions within states in the doublet. We apply these relationships to the Gamow - Teller transitions from $^{39}Ca$ to its mirror nucleus $^{39}K$.Comment: 17 pages, 2 figures, to be published in PRC. Slightly revised text with one reference adde

Molecular elasticity and the geometric phase

We present a method for solving the Worm Like Chain (WLC) model for twisting semiflexible polymers to any desired accuracy. We show that the WLC free energy is a periodic function of the applied twist with period 4 pi. We develop an analogy between WLC elasticity and the geometric phase of a spin half system. These analogies are used to predict elastic properties of twist-storing polymers. We graphically display the elastic response of a single molecule to an applied torque. This study is relevant to mechanical properties of biopolymers like DNA.Comment: five pages, one figure, revtex, revised in the light of referee's comments, to appear in PR

Co-Optimization of Blunt Body Shapes for Moving Vehicles

A method and associated system for multi-disciplinary optimization of various parameters associated with a space vehicle that experiences aerocapture and atmospheric entry in a specified atmosphere. In one embodiment, simultaneous maximization of a ratio of landed payload to vehicle atmospheric entry mass, maximization of fluid flow distance before flow separation from vehicle, and minimization of heat transfer to the vehicle are performed with respect to vehicle surface geometric parameters, and aerostructure and aerothermal vehicle response for the vehicle moving along a specified trajectory. A Pareto Optimal set of superior performance parameters is identified

The Distribution of Stellar Mass in the Pleiades

As part of an effort to understand the origin of open clusters, we present a statistical analysis of the currently observed Pleiades. Starting with a photometric catalog of the cluster, we employ a maximum likelihood technique to determine the mass distribution of its members, including single stars and both components of binary systems. We find that the overall binary fraction for unresolved pairs is 68%. Extrapolating to include resolved systems, this fraction climbs to about 76%, significantly higher than the accepted field-star result. Both figures are sensitive to the cluster age, for which we have used the currently favored value of 125 Myr. The primary and secondary masses within binaries are correlated, in the sense that their ratios are closer to unity than under the hypothesis of random pairing. We map out the spatial variation of the cluster's projected and three-dimensional mass and number densities. Finally, we revisit the issue of mass segregation in the Pleiades. We find unambiguous evidence of segregation, and introduce a new method for quantifying it.Comment: 41 pages, 14 figures To Be Published in The Astrophysical Journa