Triggered release in lipid bilayer-capped mesoporous silica nanoparticles containing SPION using an alternating magnetic field

We report here the on-command cargo controlled delivery using an alternating magnetic field (AMF) from magnetic silica mesoporous supports capped with a lipid bilayer.     

Conjugate function method for numerical conformal mappings

We present a method for numerical computation of conformal mappings from simply or doubly connected domains onto so-called canonical domains, which in our case are rectangles or annuli. The method is based on conjugate harmonic functions and properties of quadrilaterals. Several numerical examples are given.     

A lexicographic minimax algorithm for multiperiod resource allocation

Resource allocation problems are typically formulated as mathematical programs with some special structure that facilitates the development of efficient algorithms. We consider a multiperiod problem in which excess resources in one period can be used in subsequent periods. The objective minimizes lexicographically the nonincreasingly sorted vector of weighted deviations of cumulative activity levels from cumulative demands. To this end, we first develop a new minimax algorithm that minimizes the largest weighted deviation among all cumulative activity levels. The minimax algorithm handles resource constraints, ordering constraints, and lower and upper bounds. At each iteration, it fixes certain variables at their lower bounds, and sets groups of other variables equal to each other as long as no lower bounds are violated. The algorithm takes advantage of the problem's special structure; e.g., each term in the objective is a linear decreasing function of only one variable. This algorithm solves large problems very fast, orders of magnitude faster than well known linear programming packages. (The latter are, of course, not designed to solve such minimax problems efficiently.) The lexicographic procedure repeatedly employs the minimax algorithm described above to solve problems, each of the same format but with smaller dimension.     

Relaxation-based algorithms for minimax optimization problems with resource allocation applications

We consider minimax optimization problems where each term in the objective function is a continuous, strictly decreasing function of a single variable and the constraints are linear. We develop relaxation-based algorithms to solve such problems. At each iteration, a relaxed minimax problem is solved, providing either an optimal solution or a better lower bound. We develop a general methodology for such relaxation schemes for the minimax optimization problem. The feasibility tests and formulation of subsequent relaxed problems can be done by using Phase I of the Simplex method and the Farkas multipliers provided by the final Simplex tableau when the corresponding problem is infeasible. Such relaxation-based algorithms are particularly attractive when the minimax optimization problem exhibits additional structure. We explore special structures for which the relaxed problem is formulated as a minimax problem with knapsack type constraints; efficient algorithms exist to solve such problems. The relaxation schemes are also adapted to solve certain resource allocation problems with substitutable resources. There, instead of Phase I of the Simplex method, a max-flow algorithm is used to test feasibility and formulate new relaxed problems.Corresponding author.Work was partially done while visiting AT&T Bell Laboratories.     

Head-to-head vinyl polymers. III. Preparation and characterization of head-to-head poly(acrylic acid) and its esters

Head-to-head (h-h) poly(acrylic acid) (PAA) and some h-h poly(alkyl acrylates) (PRA) with methyl, ethyl, n-propyl, n-butyl, isobutyl and 2-ethylhexyl substituents were prepared by hydrolysis or esterifications of the alternating copolymer of ethylene with maleic anhydride. In general, these esterification reactions became increasingly difficult as the carbon chain in the alcohols lengthened or branched. The softening, glass transition, and degradation temperatures of the h-h polymers obtained were somewhat higher than those of the corresponding head-to-tail (h-t) polymers. The main degradation products of both h-h and h-t PRA were identified by pyrolytic gas chromatography as the alcohol and monomer. In addition, the relative ratios of the amounts of alcohol to monomer were larger for h-h than for the corresponding h-t polymers.     

Head-to-head vinyl polymers. IV. Preparation and characterization of equimolar head-to-head copolymers of acrylic acid and its esters

The alternating copolymer of ethylene with maleic anhydride was esterified with a number of aliphatic alcohols to yield its monoesters, which correspond structurally to equimolar (1:1) head-to-head (h-h) copolymers of acrylic acid with alkyl acrylates. In addition, they were methylated with diazomethane to 1:1 h-h copolymers of methyl acrylate with alkyl acrylates. For comparison the 1:1 head-to-tail (h-t) copolymers of methyl acrylate with alkyl acrylates were prepared by radical copolymerizations. Some chemical, physical, and thermal properties of these 1:1 h-h and h-t copolymers were evaluated and compared. The softening and glass transition temperatures of the 1:1 h-h copolymers were somewhat higher than those of the corresponding 1:1 h-t copolymers, which indicated that the h-h replacements made the polymer chain stiffer and less flexible. The 1:1 h-h copolymers were also observed to degrade thermally at somewhat higher temperatures and with higher rates than the 1:1 h-t copolymers. The ratio of alcohol to monomer found in the pyrolysis products was higher for the 1:1 h-h than for its respective 1:1 h-t copolymer.     

Head-to-head vinyl polymers. VI. Preparation and characterization of head-to-head poly(allyl alcohol) and its esters

Head-to-head (H–H) poly(allyl alcohol) (PAA) was prepared by the LiAlH₄ reduction of H–H poly(methyl acrylate) obtained from the methylation of alternating copolymer of ethylene with maleic anhydride. H–H poly(allyl acetate) (PAAc) and H–H poly(allyl benzoate) (PABz) were further derived by means of its acylations. All of these three H–H polymers were characterized by IR, NMR, TGA, and PGC measurements. The corresponding head-to-tail (H–T) polymers were also prepared by a similar method from the conventional H–T polymer of methyl acrylate, and characterized to allow comparison with the H–H polymers. The softening temperatures of all H–H polymers were somewhat higher than those of the respective H–T polymers, probably suggesting that the H–H placements increased the stiffness of the polymers. Unlike poly(acrylic esters) reported previously, these H–H allyl polymers were found to degrade at temperatures slightly lower than the H–T polymers. On pyrolysis at 430°C, both PAAc and PABz were also observed to release predominantly acetic acid and benzoic acid, respectively, and small quantities of the corresponding allyl ester monomers. The molar ratios of acid to ester were substantially larger for H–H polymers.     

Synthesis and Solution Properties of Ampholytic Acrylamide Ionomers

The synthesis and semiconcentrated and dilute solution properties of two series of ampholytic acrylamide ionomers, poly(acrylamide MPTMA/AMPS) and poly(acrylamide METMA/MES), are reported as a function of the ionic content and added salt concentration. The viscosity dependence on shear rate was measured with a cone/plate Brookfield viscometer for sermiconcentrated solution and with a Cannon-Ubbelohde four-bulb shear dilution capillary viscometer for dilute solution at 25 ± 0.1°C. The two series of ampholytic acrylamide ionomers showed a characteristic pseudoplastic shear-thinning behavior under both conditions. The semiconcentrated solution viscosity parameters m and n in the power-law model, η = mγ^n-1, were determined and found to be functions of the ionic content. The viscosity at selected shear rates was found to be a complex function of the salt concentration. The intrinsic viscosity [η] was determined and compared with molecular parameters determined by light scattering under identical conditions. The dilute-solution properties of the ampholytic ionomers were found to resemble the properties of neutral polyacrylamide previously reported in the literature.     

Characterization of a discontinuous epitope of the HIV envelope protein gp120 recognized by a human monoclonal antibody using chemical modification and mass spectrometric analysis

A subset of the neutralizing anti-HIV antibodies recognize epitopes on the envelope protein gp120 of the human immunodeficiency virus. These epitopes are exposed during conformational changes when gp120 binds to its primary receptor CD4. Based on chemical modification of lysine and arginine residues followed by mass spectrometric analysis, we determined the epitope on gp120 recognized by the human monoclonal antibody 559/64-D, which was previously found to be specific for the CD4 binding domain. Twenty-four lysine and arginine residues in recombinant full-length glycosylated gp120 were characterized; the relative reactivities of two lysine residues and five arginine residues were affected by the binding of 559/64-D. The data show that the epitope is discontinuous and is located in the proximity of the CD4-binding site. Additionally, the reactivities of a residue that is located in the secondary receptor binding region and several residues distant from the CD4 binding site were also altered by Ab binding. These data suggest that binding of 559/64-D induced conformational changes which result in altered surface exposure of specific amino acids distant from the CD4-binding site. Consequently, binding of 559/64-D to gp120 affects not only the CD4-binding site, which is recognized as the epitope, but appears to have a global effect on surface exposed residues of the full-length glycosylated gp120.     

Automated Hydrogen/Deuterium Exchange Electron Transfer Dissociation High Resolution Mass Spectrometry Measured at Single-Amide Resolution

Hydrogen deuterium exchange mass spectrometry (HDX-MS) is a well established method for the measurement of solution-phase deuterium incorporation into proteins, which can provide insight into protein conformational mobility. However, most HDX measurements are constrained to regions of the protein where pepsin proteolysis allows detection at peptide resolution. Recently, single-amide resolution deuterium incorporation has been achieved by limiting gas-phase scrambling in the mass spectrometer. This was accomplished by employing a combination of soft ionization and desolvation conditions coupled with the radical-driven fragmentation technique electron transfer dissociation (ETD). Here, a hybrid LTQ-Orbitrap XL is systematically evaluated for its utility in providing single-amide deuterium incorporation for differential HDX analysis of a nuclear receptor upon binding small molecule ligands. We are able to show that instrumental parameters can be optimized to minimize scrambling and can be incorporated into an established and fully automated HDX platform making differential single-amide HDX possible for bottom-up analysis of complex systems. We have applied this system to determine differential single amide resolution HDX data for the peroxizome proliferator activated receptor bound with two ligands of interest.