An ion trap-ion mobility-time of flight mass spectrometer with three ion sources for ion/ion reactions

This instrument combines the capabilities of ion/ion reactions with ion mobility (IM) and time-of-flight (TOF) measurements for conformation studies and top-down analysis of large biomolecules. Ubiquitin ions from either of two electrospray ionization (ESI) sources are stored in a three dimensional (3D) ion trap (IT) and reacted with negative ions from atmospheric sampling glow discharge ionization (ASGDI). The proton transfer reaction products are then separated by IM and analyzed via a TOF mass analyzer. In this way, ubiquitin +7 ions are converted to lower charge states down to +1; the ions in lower charge states tend to be in compact conformations with cross sections down to ～880 Ų. The duration and magnitude of the ion ejection pulse on the IT exit and the entrance voltage on the IM drift tube can affect the measured distribution of conformers for ubiquitin +7 and +6. Alternatively, protein ions are fragmented by collision-induced dissociation (CID) in the IT, followed by ion/ion reactions to reduce the charge states of the CID product ions, thus simplifying assignment of charge states and fragments using the mobility-resolved tandem mass spectrum. Instrument characteristics and the use of a new ion trap controller and software modifications to control the entire instrument are described.     

Anchor-based design of improved cholera toxin and E. coli heat-labile enterotoxin receptor binding antagonists that display multiple binding modes

The action of cholera toxin and E. coli heat-labile enterotoxin can be inhibited by blocking their binding to the cell-surface receptor GM1. We have used anchor-based design to create 15 receptor binding inhibitors that contain the previously characterized inhibitor MNPG as a substructure. In ELISA assays, all 15 compounds exhibited increased potency relative to MNPG. Binding affinities for two compounds, each containing a morpholine ring linked to MNPG via a hydrophobic tail, were characterized by pulsed ultrafiltration (PUF) and isothermal titration calorimetry (ITC). Crystal structures for these compounds bound to toxin B pentamer revealed a conserved binding mode for the MNPG moiety, with multiple binding modes adopted by the attached morpholine derivatives. The observed binding interactions can be exploited in the design of improved toxin binding inhibitors.     

The Shape of Orthogonal Cycles in Three Dimensions

Let σ be a directed cycle whose edges have each been assigned a desired direction in 3D (East, West, North, South, Up, or Down) but no length. We say that σ is a shape cycle. We consider the following problem. Does there exist an orthogonal representation Γ of σ in 3D space such that no two edges of Γ intersect except at common endpoints and such that each edge of Γ has the direction specified in σ? If the answer is positive, we say that σ is simple. This problem arises in the context of extending orthogonal graph drawing techniques from 2D to 3D. We give a combinatorial characterization of simple shape cycles that yields linear time recognition and drawing algorithms.     

Effective divisors on {\overline{\mathcal{M}}_g} associated to curves with exceptional secant planes

This article is a sequel to Cotterill (Math Zeit 267(3):549–582, 2011), in which the author studies secant planes to linear series on a curve that is general in moduli. In that paper, the author proves that a general curve has no linear series with exceptional secant planes, in a very precise sense. Consequently, it makes sense to study effective divisors on ${\overline{\mathcal{M}}_g}$ associated to curves equipped with secant-exceptional linear series. Here we describe a strategy for computing the classes of those divisors. We pay special attention to the extremal case of (2d ? 1)-dimensional series with d-secant (d ? 2)-planes, which appears in the study of Hilbert schemes of points on surfaces. In that case, modulo a combinatorial conjecture, we obtain hypergeometric expressions for tautological coefficients that enable us to deduce the asymptotics in d of our divisors’ virtual slopes.     

A random map implementation of implicit filters

Implicit particle filters for data assimilation generate high-probability samples by representing each particle location as a separate function of a common reference variable. This representation requires that a certain underdetermined equation be solved for each particle and at each time an observation becomes available. We present a new implementation of implicit filters in which we find the solution of the equation via a random map. As examples, we assimilate data for a stochastically driven Lorenz system with sparse observations and for a stochastic Kuramoto–Sivashinsky equation with observations that are sparse in both space and time.     

Underwater ambient noise on the Chukchi Sea continental slope from 2006-2009

From September 2006 to June 2009, an autonomous acoustic recorder measured ambient noise north of Barrow, Alaska on the continental slope at 235 m depth, between the Chukchi and Beaufort Seas. Mean monthly spectrum levels, selected to exclude impulsive events, show that months with open-water had the highest noise levels (80-83 dB re: 1 μPa(2)/Hz at 20-50 Hz), months with ice coverage had lower spectral levels (70 dB at 50 Hz), and months with both ice cover and low wind speeds had the lowest noise levels (65 dB at 50 Hz). During ice covered periods in winter-spring there was significant transient energy between 10 and 100 Hz from ice fracture events. During ice covered periods in late spring there were significantly fewer transient events. Ambient noise increased with wind speed by ~ 1 dB/m/s for relatively open-water (0%-25% ice cover) and by ~ 0.5 dB/m/s for nearly complete ice cover (> 75%). In September and early October for all years, mean noise levels were elevated by 2-8 dB due to the presence of seismic surveys in the Chukchi and Beaufort Seas.     

Impact of woven fabric: Experiments and mesostructure-based continuum-level simulations

Woven fabric is an increasingly important component of many defense and commercial systems, including deployable structures, restraint systems, numerous forms of protective armor, and a variety of structural applications where it serves as the reinforcement phase of composite materials. With the prevalence of these systems and the desire to explore new applications, a comprehensive, computationally efficient model for the deformation of woven fabrics is needed. However, modeling woven fabrics is difficult due, in particular, to the need to simulate the response both at the scale of the entire fabric and at the meso-level, the scale of the yarns that compose the weave. Here, we present finite elements for the simulation of the three-dimensional, high-rate deformation of woven fabric. We employ a continuum-level modeling technique that, through the use of an appropriate unit cell, captures the evolution of the mesostructure of the fabric without explicitly modeling every yarn. Displacement degrees of freedom and degrees of freedom representing the change in crimp amplitude of each yarn family fully determine the deformed geometry of the mesostructure of the fabric, which in turn provides, through the constitutive relations, the internal nodal forces. In order to verify the accuracy of the elements, instrumented ballistic impact experiments with projectile velocities of 22-550 m/s were conducted on single layers of Kevlar^® fabric. Simulations of the experiments demonstrate that the finite elements are capable of efficiently simulating large, complex structures.     

Novel Solventless Extraction Technique to Preserve Cannabinoid and Terpenoid Profiles of Fresh Cannabis Inflorescence

Despite its use by humans for thousands of years, the technology of cannabis usage and extraction is still evolving. Given that the primary pharmacological compounds of interest are cannabinoid and terpenoids found in greatest abundance in capitate glandular trichomes of unfertilized female inflorescences, it is surprising that older techniques of hashish making have received less technological advancement. The purpose of this study was to employ organically grown cannabis and to isolate pure trichomes from freshly picked flowers via exposure to vapor from solid CO₂, commonly known as “dry ice”, followed by their isolation via sifting through a 150 µ screens while maintaining the cold chain. Biochemical analysis was undertaken on fresh flower, frozen-sifted flower by-products, treated trichomes (Kryo-Kief™), dried flower, dried sifted flower by-product and dried kief. The dry ice process successfully concentrated cannabinoid content as high as 60.7%, with corresponding concentration and preservation of monoterpenoids encountered in fresh flower that are usually lost during the conventional cannabis drying and curing process. The resulting dried sifted flower by-product after dry ice processing remains a usable commodity. This approach may be of interest to pharmaceutical companies and supplement producers pursuing cannabis-based medicine development with an eye toward full synergy of ingredients harnessing the entourage effect.     

Exploring Microfluidic Routes to Microgels of Biological Polymers

Polymer microgels in the size range from several micrometers to hundreds of micrometers are used in the pharmaceutical, cosmetics, nutrition, pesticide, and food industries, as well as in the encapsulation of cells. To date, a broad range of strategies for the generation of polymer microgels exist, however, these methods involve multistage processes, do not utilize biocompatible components or do not allow precise control of the dimensions and internal structure of the microgels. Recently, microfluidic strategies for the production of polymer particles have offered precise control over the shapes, morphologies, and size distributions of polymer colloids. This paper discusses the most recent results obtained by the authors in the area of the microfluidic production of biopolymer microgels. It provides a brief review of the microfluidic methods for the continuous synthesis and fabrication of microgels, sets the criteria for the successful microfluidic generation of biomicrogels, and describes two methods for the preparation of microgels by microfluidic means. The article concludes with a summary and an outlook.