Utilizing Paper-Based Devices for Antimicrobial-Resistant Bacteria Detection

Antimicrobial resistance (AMR), the ability of a bacterial species to resist the action of an antimicrobial drug, has been on the rise due to the widespread use of antimicrobial agents. Per the World Health Organization, AMR has an estimated annual cost of USD 34 billion in the US and is predicted to be the number one cause of death worldwide by 2050. One way AMR bacteria can spread, and by which individuals can contract AMR infections, is through contaminated water. Monitoring AMR bacteria in the environment currently requires that samples be transported to a central laboratory for slow and labor intensive tests. We have developed an inexpensive assay using paper-based analytical devices (PADs) that can test for the presence of β-lactamase-mediated resistance. To demonstrate viability, the PAD was used to detect β-lactam resistance in wastewater and sewage and identified resistance in individual bacterial species isolated from environmental water sources.     

An open source ion gate pulser for ion mobility spectrometry

Excluding the ion source, an ion mobility spectrometer is fundamentally comprised of drift chamber, ion gate, pulsing electronics, and a mechanism for amplifying and recording ion signals. Historically, the solutions to each of these challenges have been custom and rarely replicated exactly. For the IMS research community few detailed resources exist that explicitly detail the construction and operation of ion mobility systems. In an effort to address this knowledge gap we outline a solution to one of the key aspects of a drift tube ion mobility system, the ion gate pulser. Bradbury-Nielsen or Tyndall ion gates are found in nearly every research-grade and commercial IMS system. While conceptually simple, these gate structures often require custom, high-voltage, floating electronics. In this report we detail the operation and performance characteristics of a wifi-enabled, MOSFET-based pulser design that uses a lithium-polymer battery and does not require high voltage isolation transformers. Currently, each output of this circuit follows a TTL signal with ~20 ns rise and fall times, pulses up to +/? 200 V, and is entirely isolated using fiber optics. Detailed schematics and source code are provided to enable continued use of robust pulsing electronics that ease experimental efforts for future comparison.     

Heterogeneous surface-to-air missile defense battery location: a game theoretic approach

In the context of an air defense missile-and-interceptor engagement, a challenge for the defender is that surface-to-air missile batteries often must be located to protect high-value targets dispersed over a vast area, subject to which an attacker may observe the disposition of batteries and subsequently develop and implement an attack plan. To model this scenario, we formulate a two-player, extensive form, three-stage, perfect information, zero-sum game that accounts for, respectively, a defender’s location of batteries, an attacker’s launch of missiles against targets, and a defender’s assignment of interceptor missiles from batteries to incoming attacker missiles. The resulting trilevel math programming formulation cannot be solved via direct optimization, and it is not suitable to solve via full enumeration for realistically-sized instances. We instead adapt the game tree search technique Double Oracle, within which we embed either of two alternative heuristics to solve an important subproblem for the attacker. We test and compare these solution methods to solve a designed set of 52 instances having parametric variations, from which we derive insights regarding the nature of the underlying problem. Enhancing the solution methods with alternative initialization strategies, our superlative methodology attains the optimal solution for over 75% of the instances tested and solutions within 3% of optimal, on average, for the remaining 25% of the instances, and it is promising for realistically-sized instances, scaling well with regard to computational effort.     

Rotation-Inversion Isomerization of Tertiary Carbamates: Potential Energy Surface Analysis of Multi-Paths Isomerization Using Boltzmann Statistics

Potential energy surface (PES) analyses at the SMD[MP2/6–311++G(d,p)] level and higher-level energies up to MP4(fc,SDTQ) are reported for the fluorinated tertiary carbamate N-ethyl-N-(2,2,2-trifluoroethyl) methyl carbamate ( VII ) and its parent system N,N-dimethyl methyl carbamate ( VI ). Emphasis is placed on the analysis of the rotational barrier about the CN carbamate bond and its interplay with the hybridization of the N-lone pair (NLP). All rotational transition state (TS) structures were found by computation of 1D relaxed rotational profiles but only 2D PES scans revealed the rotation-inversion paths in a compelling fashion. We found four unique chiral minima of VII , one pair each of E- and Z-rotamers, and we determined the eight unique rotational TS structures associated with every possible E/Z-isomerization path. It is a significant finding that all TS structures feature N-pyramidalization whereas the minima essentially contain sp²-hybridized nitrogen. We will show that the TS stabilities are affected by the synergetic interplay between NLP/CO₂ repulsion minimization, NLP→σ^*(CO) negative hyperconjugation, and two modes of intramolecular through-space electrostatic stabilization. We demonstrate how Boltzmann statistics must be applied to determine the predicted experimental rotational barrier based on the energetics of all eight rotamerization pathways. The computed barrier for VII is in complete agreement with the experimentally measured barrier of the very similar fluorinated carbamate N-Boc-N-(2,2,2-trifluoroethyl)-4-aminobutan-1-ol II . NMR properties of VII were calculated with a variety of density functional/basis set combinations and Boltzmann averaging over the E- and Z-rotamers at our best theoretical level results in good agreement with experimental chemical shifts δ(¹³C) and J(¹³C,¹⁹F) coupling constants of II (within 6 %).     

Match statistics for sequence-based alleles in profiles from forensic PCR-mps kits

The first autosomal sequence-based allele (aka SNP-STR haplotype) frequency database for forensic massively parallel sequencing (MPS) has been published, thereby removing one of the remaining barriers to implementing MPS in casework. The database was developed using a specific set of flank trim sites. If different trim sites or different kits with different primers are used for casework, then SNP-STR haplotypes may be detected that do not have frequencies in the database. We describe a procedure to address calculation of match probabilities when casework samples are generated using an MPS kit with different trim sites than those present in the relevant population frequency database. The procedure provides a framework for comparison of any MPS kit or database combination while also accommodating comparison of MPS and CE profiles.     

Investigating microcrystalline cellulose crystallinity using Raman spectroscopy

Cellulose - Microcrystalline cellulose (MCC) is a semi-crystalline material with inherent variable crystallinity due to raw material source and variable manufacturing conditions. MCC crystallinity...     

Structural and Electronic Influences on Rates of Tertpyridine−Amine CoIII−H Formation During Catalytic H2 Evolution in an Aqueous Environment

In this work, the differences in catalytic performance for a series of Co hydrogen evolution catalysts with different pentadentate polypyridyl ligands (L), have been rationalized by examining elementary steps of the catalytic cycle using a combination of electrochemical and transient pulse radiolysis (PR) studies in aqueous solution. Solvolysis of the [Co^II−Cl]⁺ species results in the formation of [Co^II(κ⁴-L)(OH₂)]²⁺. Further reduction produces [Co^I(κ⁴-L)(OH₂)]⁺, which undergoes a rate-limiting structural rearrangement to [Co^I(κ⁵-L)]⁺ before being protonated to form [Co^III−H]²⁺. The rate of [Co^III−H]²⁺ formation is similar for all complexes in the series. Using E_1/2 values of various Co species and pK_a values of [Co^III−H]²⁺ estimated from PR experiments, we found that while the protonation of [Co^III−H]²⁺ is unfavorable, [Co^II−H]⁺ reacts with protons to produce H₂. The catalytic activity for H₂ evolution tracks the hydricity of the [Co^II−H]⁺ intermediate.     

Interphotoreceptor Retinoid‐Binding Protein Protects Retinoids from Photodegradation

Retinol degrades rapidly in light into a variety of photoproducts. It is remarkable that visual cycle retinoids can evade photodegradation as they are exchanged between the photoreceptors, retinal pigment epithelium and Müller glia. Within the interphotoreceptor matrix, all‐trans retinol, 11‐cis retinol and retinal are bound by interphotoreceptor retinoid‐binding protein (IRBP). Apart from its role in retinoid trafficking and targeting, could IRBP have a photoprotective function? HPLC was used to evaluate the ability of IRBP to protect all‐trans and 11‐cis retinols from photodegradation when exposed to incandescent light (0 to 8842 μW cm^?2); time periods of 0–60 min, and bIRBP: retinol molar ratios of 1:1 to 1:5. bIRBP afforded a significant prevention of both all‐trans and 11‐cis retinol to rapid photodegradation. The effect was significant over the entire light intensity range tested, and extended to the bIRBP: retinol ratio 1:5. In view of the continual exposure of the retina to light, and the high oxidative stress in the outer retina, our results suggest IRBP may have an important protective role in the visual cycle by reducing photodegradation of all‐trans and 11‐cis retinols. This role of IRBP is particularly relevant in the high flux conditions of the cone visual cycle.     

Conformational Analysis of the 1,3‐Oxaphosphorinanes Formed from α,β‐Unsaturated Aldehydes and the (Hydroxymethyl)phosphines RP(CH2OH)2 (R = Ph or CH2OH)

Equimolar reactions of cinnamaldehyde or its 3,5‐dimethoxy‐4‐hydroxy derivative (sinapaldehyde) with RP(CH₂OH)₂ (R = Ph or CH₂OH) were studied in MeOH or CD₃OD at room temperature by NMR spectroscopy. In MeOH, nucleophilic attack of the phosphine at the C?C bond, with concomitant loss of CH₂O, affords the tertiary phosphine HOCH₂P(R)CH(Ar)CH₂CHO ( 3 ) that rapidly converts mainly into a 1,3‐oxaphosphorinane derivative ( 5 ) formed as a mixture of four diastereomers. Conformational analysis reveals that the Ar group in these is exclusively in an equatorial position while the OH and R groups can be equatorial‐oriented or axial‐oriented. In CD₃OD, 1,3‐oxaphosphorinanes monodeuterated in the C5 position are obtained as a mixture of eight diastereomers where the dominate diastereomers have an axial D‐atom. Diastereomeric ratios depend on the nature of the Ar and R groups.     

Palladium(II)‐Catalyzed Allylic C?H Oxidation of Hindered Substrates Featuring Tunable Selectivity Over Extent of Oxidation

The use of Oxone and a palladium(II) catalyst enables the efficient allylic C H oxidation of sterically hindered α‐quaternary lactams which are unreactive under known conditions for similar transformations. This simple, safe, and effective system for C H activation allows for unusual tunable selectivity between a two‐electron oxidation to the allylic acetates and a four‐electron oxidation to the corresponding enals, with the dominant product depending on the presence or absence of water. The versatile synthetic utility of both the allylic acetate and enal products accessible through this methodology is also demonstrated.