U.S. Army Combat Capabilities Development Command Chemical Biological Center

A new ion source has been developed for rapid, noncontact analysis of materials at ambient pressure and at ground potential. The new source, termed DART (for "Direct Analysis in Real Time"), is based on the reactions of electronic or vibronic excited-state species with reagent molecules and polar or nonpolar analytes. DART has been installed on a high-resolution time-of-flight mass spectrometer (TOFMS) that provides improved selectivity and accurate elemental composition assignment through exact mass measurements. Although DART has been applied to the analysis of gases, liquids, and solids, a unique application is the direct detection of chemicals on surfaces without requiring sample preparation, such as wiping or solvent extraction. DART has demonstrated success in sampling hundreds of chemicals, including chemical agents and their signatures, pharmaceutics, metabolites, peptides and oligosaccharides, synthetic organics, organometallics, drugs of abuse, explosives, and toxic industrial chemicals. These species were detected on various surfaces, such as concrete, asphalt, human skin, currency, airline boarding passes, business cards, fruits, vegetables, spices, beverages, body fluids, horticultural leaves, cocktail glasses, and clothing. DART employs no radioactive components and is more versatile than devices using radioisotope-based ionization. Because its response is instantaneous, DART provides real-time information, a critical requirement for screening or high throughput.

Human acetylcholinesterase (AChE) is a significant target for therapeutic drugs. Here we present high resolution crystal structures of human AChE, alone and in complexes with drug ligands; donepezil, an Alzheimer's disease drug, binds differently to human AChE than it does to Torpedo AChE. These crystals of human AChE provide a more accurate platform for further drug development than previously available.

We propose a method to use artificial neural networks to approximate light scattering by multilayer nanoparticles. We find that the network needs to be trained on only a small sampling of the data to approximate the simulation to high precision. Once the neural network is trained, it can simulate such optical processes orders of magnitude faster than conventional simulations. Furthermore, the trained neural network can be used to solve nanophotonic inverse design problems by using back propagation, where the gradient is analytical, not numerical.

Metal–organic frameworks (MOFs) with the Zr6O4(OH)4 secondary building unit (SBU) have been of particular interest for potential commercial and industrial uses because they can be easily tailored and are reported to be chemically and thermally stable. However, we show that there are significant changes in chemical and thermal stability of Zr6O4(OH)4 MOFs with the incorporation of different organic linkers. As the number of aromatic rings is increased from one to two in 1,4-benzene dicarboxylate (UiO-66, ZrMOF–BDC) and 4,4′-biphenyl dicarboxylate (UiO-67, ZrMOF–BPDC), the Zr6O4(OH)4 SBU becomes more susceptible to chemical degradation by water and hydrochloric acid. Furthermore, as the linker is replaced with 2,2′-bipyridine-5,5′-dicarboxylate (ZrMOF–BIPY) the chemical stability decreases further as the MOF is susceptible to chemical breakdown by protic chemicals such as methanol and isopropanol. The results reported here bring into question the superior structural stability of the UiO-67 analogs as reported by others. Furthermore, the degradation mechanisms proposed here may be applied to other classes of MOFs containing aromatic dicarboxylate organic linkers, in order to predict their structural stability upon exposure to solvents.

Metal–organic frameworks (MOFs) with metal–carboxylate bonds, including Cu-BTC (HKUST-1), Mg-MOF-74 (Mg/DOBDC), and UiO-66, have been shown to have varying degrees of water stability. The three MOFs in this study are three of the most highly studied MOFs in the literature. We investigate here how each MOF degrades at several temperature and humidity conditions over the course of 28 days. At conditions of 90% relative humidity (RH) and 25 °C, water uptake for Cu-BTC is shown to be higher than at 90% RH and 40 °C, causing the degradation of the inner structure of Cu-BTC to occur more readily at the lower temperature. However the external surfaces of Cu-BTC degrade more readily, as shown through SEM images, at conditions of 90% RH and 40 °C. Mg-MOF-74 has a nearly complete loss of surface area after just one day of exposure to each of the conditions studied, however the PXRD patterns show only a change in the [100] peak. We offer here a novel mechanism for the degradation of Mg-MOF-74, involving a 6-coordinate Mg intermediate, which leaves the 1-dimensional channels of Mg-MOF-74 intact. Furthermore, we conclude that UiO-66 is stable to each of the aging conditions for the full 28 days of this study.

Immobilized enzymes typically have greater thermal and operational stability than their soluble form. Here we report that for the first time, a nerve agent detoxifying enzyme, organophosphorus acid anhydrolase (OPAA), has been successfully encapsulated into a water-stable zirconium metal-organic framework (MOF). This MOF features a hierarchical mesoporous channel structure and exhibits a 12 wt % loading capacity of OPAA. The thermal and long-term stabilities of OPAA are both significantly enhanced after immobilization.

UV radiation from the sun is the primary germicide in the environment. The goal of this study was to estimate inactivation of viruses by solar exposure. We reviewed published reports on 254-nm UV inactivation and tabulated the sensitivities of a wide variety of viruses, including those with double-stranded DNA, single-stranded DNA, double-stranded RNA, or single-stranded RNA genomes. We calculated D(37) values (fluence producing on average one lethal hit per virion and reducing viable virus to 37%) from all available data. We defined "size-normalized sensitivity" (SnS) by multiplying UV(254) sensitivities (D(37) values) by the genome size, and SnS values were relatively constant for viruses with similar genetic composition. In addition, SnS values were similar for complete virions and their defective particles, even when the corresponding D(37) values were significantly different. We used SnS to estimate the UV(254) sensitivities of viruses for which the genome composition and size were known but no UV inactivation data were available, including smallpox virus, Ebola, Marburg, Crimean-Congo, Junin, and other hemorrhagic viruses, and Venezuelan equine encephalitis and other encephalitis viruses. We compiled available data on virus inactivation as a function of wavelength and calculated a composite action spectrum that allowed extrapolation from the 254-nm data to solar UV. We combined our estimates of virus sensitivity with solar measurements at different geographical locations to predict virus inactivation. Our predictions agreed with the available experimental data. This work should be a useful step to understanding and eventually predicting the survival of viruses after their release in the environment.

(IV, IV, IV, IV), satisfying all experimental constraints and reproducing all observables. By contrast, it was impossible to construct a consistent cycle based on the low-valent scheme for all S states. Instead, the low-valent models developed here may provide new insight into the over-reduced S states and the states involved in the assembly of the catalytically active water oxidizing cluster.

Titration of microorganisms in infectious or environmental samples is a corner stone of quantitative microbiology. A simple method is presented to estimate the microbial counts obtained with the serial dilution technique for microorganisms that can grow on bacteriological media and develop into a colony. The number (concentration) of viable microbial organisms is estimated from a single dilution plate (assay) without a need for replicate plates. Our method selects the best agar plate with which to estimate the microbial counts, and takes into account the colony size and plate area that both contribute to the likelihood of miscounting the number of colonies on a plate. The estimate of the optimal count given by our method can be used to narrow the search for the best (optimal) dilution plate and saves time. The required inputs are the plate size, the microbial colony size, and the serial dilution factors. The proposed approach shows relative accuracy well within ±0.1log10 from data produced by computer simulations. The method maintains this accuracy even in the presence of dilution errors of up to 10% (for both the aliquot and diluent volumes), microbial counts between 10(4) and 10(12) colony-forming units, dilution ratios from 2 to 100, and plate size to colony size ratios between 6.25 to 200.

Metal organic frameworks (MOFs) are a leading class of porous materials for a wide variety of applications, but many of them have been shown to be unstable toward water. Cu-BTC (1,3,5 benzenetricarboxylic acid, BTC) was treated with a plasma-enhanced chemical vapor deposition (PECVD) of perfluorohexane creating a hydrophobic form of Cu-BTC. It was found that the treated Cu-BTC could withstand high humidity and even submersion in water much better than unperturbed Cu-BTC. Through Monte Carlo simulations it was found that perfluorohexane sites itself in such a way within Cu-BTC as to prevent the formation of water clusters, hence preventing the decomposition of Cu-BTC by water. This PECVD of perfluorohexane could be exploited to widen the scope of practical applications of Cu-BTC and other MOFs.

We report the synthesis and characterization of a water-stable zirconium metal-organic framework (MOF), NU-1003, featuring the largest mesoporous aperture known for a zirconium MOF. This material has been used to immobilize the nerve agent hydrolyzing enzyme, organophosphorus acid anhydrolase (OPAA). The catalytic efficiency of immobilized OPAA in nanosized NU-1003 is significantly increased compared to that of OPAA immobilized in microsized NU-1003 and even exceeds that of the free OPAA enzyme. This paper highlights a method for rapid and highly efficient hydrolysis of nerve agents using nanosized enzyme carriers.

Dermal interstitial fluid (ISF) is an underutilized information-rich biofluid potentially useful in health status monitoring applications whose contents remain challenging to characterize. Here, we present a facile microneedle approach for dermal ISF extraction with minimal pain and no blistering for human subjects and rats. Extracted ISF volumes were sufficient for determining transcriptome, and proteome signatures. We noted similar profiles in ISF, serum, and plasma samples, suggesting that ISF can be a proxy for direct blood sampling. Dynamic changes in RNA-seq were recorded in ISF from induced hypoxia conditions. Finally, we report the first isolation and characterization, to our knowledge, of exosomes from dermal ISF. The ISF exosome concentration is 12-13 times more enriched when compared to plasma and serum and represents a previously unexplored biofluid for exosome isolation. This minimally invasive extraction approach can enable mechanistic studies of ISF and demonstrates the potential of ISF for real-time health monitoring applications.

Recently, polymer-metal-organic frameworks (polyMOFs) were reported as a new class of hybrid porous materials that combine advantages of both organic polymers and crystalline MOFs. Herein, we report a bridging coligand strategy to prepare new types of polyMOFs, demonstrating that polyMOFs are compatible with additional MOF architectures besides that of the earlier reported IRMOF-1 type polyMOF. Gas sorption studies revealed that these polyMOF materials exhibited relatively high CO2 sorption but very low N2 sorption, making them promising materials for CO2/N2 separations. Moreover, these polyMOFs demonstrated exceptional water stability attributed to the hydrophobicity of polymer ligands as well as the cross-linking of the polymer chains within the MOF.

The regulatory network for the uptake of Escherichia coli autoinducer 2 (AI-2) is comprised of a transporter complex, LsrABCD; its repressor, LsrR; and a cognate signal kinase, LsrK. This network is an integral part of the AI-2 quorum-sensing (QS) system. Because LsrR and LsrK directly regulate AI-2 uptake, we hypothesized that they might play a wider role in regulating other QS-related cellular functions. In this study, we characterized physiological changes due to the genomic deletion of lsrR and lsrK. We discovered that many genes were coregulated by lsrK and lsrR but in a distinctly different manner than that for the lsr operon (where LsrR serves as a repressor that is derepressed by the binding of phospho-AI-2 to the LsrR protein). An extended model for AI-2 signaling that is consistent with all current data on AI-2, LuxS, and the LuxS regulon is proposed. Additionally, we found that both the quantity and architecture of biofilms were regulated by this distinct mechanism, as lsrK and lsrR knockouts behaved identically. Similar biofilm architectures probably resulted from the concerted response of a set of genes including flu and wza, the expression of which is influenced by lsrRK. We also found for the first time that the generation of several small RNAs (including DsrA, which was previously linked to QS systems in Vibrio harveyi) was affected by LsrR. Our results suggest that AI-2 is indeed a QS signal in E. coli, especially when it acts through the transcriptional regulator LsrR.

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ions that promote further homogeneous MOF growth. Insights presented here improve understanding of compatibility between active MOF materials and substrate surfaces, which we believe will help advanced MOF composite materials for a variety of useful functions.

The present publication surveys several applications of in silico (i.e., computational) toxicology approaches across different industries and institutions. It highlights the need to develop standardized protocols when conducting toxicity-related predictions. This contribution articulates the information needed for protocols to support in silico predictions for major toxicological endpoints of concern (e.g., genetic toxicity, carcinogenicity, acute toxicity, reproductive toxicity, developmental toxicity) across several industries and regulatory bodies. Such novel in silico toxicology (IST) protocols, when fully developed and implemented, will ensure in silico toxicological assessments are performed and evaluated in a consistent, reproducible, and well-documented manner across industries and regulatory bodies to support wider uptake and acceptance of the approaches. The development of IST protocols is an initiative developed through a collaboration among an international consortium to reflect the state-of-the-art in in silico toxicology for hazard identification and characterization. A general outline for describing the development of such protocols is included and it is based on in silico predictions and/or available experimental data for a defined series of relevant toxicological effects or mechanisms. The publication presents a novel approach for determining the reliability of in silico predictions alongside experimental data. In addition, we discuss how to determine the level of confidence in the assessment based on the relevance and reliability of the information.

Abstract We herein report a new facile strategy to ellipsoidal block copolymer nanoparticles that exhibit a pH‐triggered anistropic swelling profile. In a first step, elongated particles with an axially stacked lamellae structure are selectively prepared by utilizing functional surfactants to control the phase separation of symmetric polystyrene‐ b ‐poly(2‐vinylpyridine) (PS‐ b ‐P2VP) in dispersed droplets. In a second step, the dynamic shape change is realized by cross‐linking the P2VP domains, thereby connecting glassy PS discs with pH‐sensitive hydrogel actuators.

Adsorption equilibria and NMR experiments were performed to study the adsorption and interactions of ammonia with metal-organic framework (MOF) HKUST-1, or Cu(3)(BTC)(2) (BTC = 1,3,5-benzenetricarboxylate). Ammonia capacities determined from chemical breakthrough measurements show significantly higher uptake capacities than from adsorption alone, suggesting a stronger interaction involving a potential reaction with the Cu(3)(BTC)(2) framework. Indeed, (1)H MAS NMR reveals that a major disruption of the relatively simple spectrum of Cu(3)(BTC)(2) occurs to generate a composite spectrum consistent with Cu(OH)(2) and (NH(4))(3)BTC species under humid conditions-the anticipated products of a copper(II) carboxylate reacted with limited ammonia. These species are not detected under dry conditions; however, reaction stoichiometry combined with XRD results suggests the partial formation of an indeterminate diammine copper (II) complex with some residual Cu(3)(BTC)(2) structure retained. Cu(II)-induced paramagnetic shifts exhibited by various species in (1)H and (13)C MAS NMR spectra are consistent with model compounds and previous literature. Although results show extensive ammonia capacity of Cu(3)(BTC)(2), much of the capacity is due to reaction with the structure itself, causing a permanent loss in porosity and structural integrity.

Highly tunable metal–organic framework (MOF) materials, including, for example, UiO-66-NH2, are known to be effective catalysts to degrade chemical warfare agents (CWAs) with half-lives near 1 min. Therefore, many researchers have been actively working on producing supported MOF materials to improve application effectiveness by using relatively slow solvothermal synthesis or repetitious stepwise layer-by-layer methods. Herein, we demonstrate a facile route to rapidly assemble presynthesized UiO-66-NH2 crystals onto nonwoven polypropylene (PP) fibrous mats at ambient temperature. Crystal assembly is chemically directed using β-cyclodextrin (β-CD) and cetyltrimethylammonium bromide (CTAB) as surfactant assembly agents, where the agents quickly (within 5 min) self-assemble on the crystal surface and promote physically robust chemical surface attachment while simultaneously impeding solution-phase crystal agglomeration. Furthermore, we find that when the PP is preconditioned using conformal metal oxide thin films, including Al2O3, TiO2, or ZnO formed via atomic layer deposition (ALD), the hydrophilic metal oxide surface further helps improve assembly uniformity and MOF mass loading, producing MOF crystal loading as high as 40 wt % and an overall BET surface area exceeding 200 m2/g(MOF+Fiber). Using these surface-assembled MOFs, we observe catalytic degradation of dimethyl 4-nitrophenyl phosphate (DMNP), a CWA simulant, with a half-life of less than 5 min.