S-cysteinylated albumin and methionine-oxidized apolipoprotein A-I (apoA-I) have been posed as candidate markers of diseases associated with oxidative stress. Here, a dilute-and-shoot form of LC–electrospray ionization–MS requiring half a microliter of blood plasma was employed to simultaneously quantify the relative abundance of these oxidized proteoforms in samples stored at −80 °C, −20 °C, and room temperature and exposed to multiple freeze-thaw cycles and other adverse conditions in order to assess the possibility that protein oxidation may occur as a result of poor sample storage or handling. Samples from a healthy donor and a participant with poorly controlled type 2 diabetes started at the same low level of protein oxidation and behaved similarly; significant increases in albumin oxidation via S-cysteinylation were found to occur within hours at room temperature and days at −20 °C. Methionine oxidation of apoA-I took place on a longer time scale, setting in after albumin oxidation reached a plateau. Freeze–thaw cycles had a minimal effect on protein oxidation. In matched collections, protein oxidation in serum was the same as that in plasma. Albumin and apoA-I oxidation were not affected by sample headspace or the degree to which vials were sealed. ApoA-I, however, was unexpectedly found to oxidize faster in samples with lower surface-area-to-volume ratios. An initial survey of samples from patients with inflammatory conditions normally associated with elevated oxidative stress-including acute myocardial infarction and prostate cancer—demonstrated a lack of detectable apoA-I oxidation. Albumin S-cysteinylation in these samples was consistent with known but relatively brief exposures to temperatures above −30 °C (the freezing point of blood plasma). Given their properties and ease of analysis, these oxidized proteoforms, once fully validated, may represent the first markers of blood plasma specimen integrity based on direct measurement of oxidative molecular damage that can occur under suboptimal storage conditions.

In recent years, a substantial amount of research has been focused on identifying suitable interfacial layers in organic light-emitting diodes and organic solar cells which has efficient charge transport properties. In this work, a very thin layer of AgOx is deposited on top of the ITO layer along with PEDOT:PSS and is observed that the solar cells having the AgOx interfacial layer showed a 28% increase in power conversion efficiency in comparison to that of the control cell. The enhancement in efficiency has been ascribed to improvements in fill factor as well as the increase in shunt resistance and decrease in the series resistance of the solar cells. An equivalent circuit model is also provided to understand the changes in the series and shunt resistances in the AgOx modified devices.

The objective of articulating sustainability visions through modeling is to enhance the outcomes and process of visioning in order to successfully move the system toward a desired state. Models emphasize approaches to develop visions that are viable and resilient and are crafted to adhere to sustainability principles. This approach is largely assembled from visioning processes (resulting in descriptions of desirable future states generated from stakeholder values and preferences) and participatory modeling processes (resulting in systems-based representations of future states co-produced by experts and stakeholders). Vision modeling is distinct from normative scenarios and backcasting processes in that the structure and function of the future desirable state is explicitly articulated as a systems model. Crafting, representing and evaluating the future desirable state as a systems model in participatory settings is intended to support compliance with sustainability visioning quality criteria (visionary, sustainable, systemic, coherent, plausible, tangible, relevant, nuanced, motivational and shared) in order to develop rigorous and operationalizable visions. We provide two empirical examples to demonstrate the incorporation of vision modeling in research practice and education settings. In both settings, vision modeling was used to develop, represent, simulate and evaluate future desirable states. This allowed participants to better identify, explore and scrutinize sustainability solutions.

Bacterial lipopolysaccharides (LPS) are structural components of the outer membranes of Gram-negative bacteria and also are potent inducers of inflammation in mammals. Higher vertebrates are extremely sensitive to LPS, but lower vertebrates, like fish, are resistant to their systemic toxic effects. However, the effects of LPS on the fish intestinal mucosa remain unknown. Edwardsiella ictaluri is a primitive member of the Enterobacteriaceae family that causes enteric septicemia in channel catfish (Ictalurus punctatus). E. ictaluri infects and colonizes deep lymphoid tissues upon oral or immersion infection. Both gut and olfactory organs are the primary sites of invasion. At the systemic level, E. ictaluri pathogenesis is relatively well characterized, but our knowledge about E. ictaluri intestinal interaction is limited. Recently, we observed that E. ictaluri oligo-polysaccharide (O-PS) LPS mutants have differential effects on the intestinal epithelia of orally inoculated catfish. Here we evaluate the effects of E. ictaluri O-PS LPS mutants by using a novel catfish intestinal loop model and compare it to the rabbit ileal loop model inoculated with Salmonella enterica serovar Typhimurium LPS. We found evident differences in rabbit ileal loop and catfish ileal loop responses to E. ictaluri and S. Typhimurium LPS. We determined that catfish respond to E. ictaluri LPS but not to S. Typhimurium LPS. We also determined that E. ictaluri inhibits cytokine production and induces disruption of the intestinal fish epithelia in an O-PS-dependent fashion. The E. ictaluri wild type and ΔwibT LPS mutant caused intestinal tissue damage and inhibited proinflammatory cytokine synthesis, in contrast to E. ictaluri Δgne and Δugd LPS mutants. We concluded that the E. ictaluri O-PS subunits play a major role during pathogenesis, since they influence the recognition of the LPS by the intestinal mucosal immune system of the catfish. The LPS structure of E. ictaluri mutants is needed to understand the mechanism of interaction.

It has become common for sustainability science and resilience theory to be considered as complementary approaches. Occasionally the terms have been used interchangeably. Although these two approaches share some working principles and objectives, they also are based on some distinct assumptions about the operation of systems and how we can best guide these systems into the future. Each approach would benefit from some scholars keeping sustainability science and resilience theory separate and focusing on further developing their distinctiveness and other scholars continuing to explore them in combination. Three areas of research in which following different procedures might be beneficial are whether to prioritize outcomes or system dynamics, how best to take advantage of community input, and increasing the use of knowledge of the past as a laboratory for potential innovations.

Signatures of nonlinear and non-Gaussian dynamics in time-resolved linear and nonlinear (correlation) 2D spectra are analyzed in a model considering a linear plus quadratic dependence of the spectroscopic transition frequency on a Gaussian nuclear coordinate of the thermal bath (quadratic coupling). This new model is contrasted to the commonly assumed linear dependence of the transition frequency on the medium nuclear coordinates (linear coupling). The linear coupling model predicts equality between the Stokes shift and equilibrium correlation functions of the transition frequency and time-independent spectral width. Both predictions are often violated, and we are asking here the question of whether a nonlinear solvent response and/or non-Gaussian dynamics are required to explain these observations. We find that correlation functions of spectroscopic observables calculated in the quadratic coupling model depend on the chromophore’s electronic state and the spectral width gains time dependence, all in violation of the predictions of the linear coupling models. Lineshape functions of 2D spectra are derived assuming Ornstein–Uhlenbeck dynamics of the bath nuclear modes. The model predicts asymmetry of 2D correlation plots and bending of the center line. The latter is often used to extract two-point correlation functions from 2D spectra. The dynamics of the transition frequency are non-Gaussian. However, the effect of non-Gaussian dynamics is limited to the third-order (skewness) time correlation function, without affecting the time correlation functions of higher order. The theory is tested against molecular dynamics simulations of a model polar–polarizable chromophore dissolved in a force field water.

The context in which many self-governed commons systems operate will likely be significantly altered as globalization processes play out over the next few decades. Such dramatic changes will induce some systems to fail and subsequently to be transformed, rather than merely adapt. Despite this possibility, research on globalization-induced transformations of social-ecological systems (SESs) is still underdeveloped. We seek to help fill this gap by exploring some patterns of transformation in SESs and the question of what factors help explain the persistence of cooperation in the use of common-pool resources through transformative change. Through the analysis of 89 forest commons in South Korea that experienced such transformations, we found that there are two broad types of transformation, cooperative and noncooperative. We also found that two system-level properties, transaction costs associated group size and network diversity, may affect the direction of transformation. SESs with smaller group sizes and higher network diversity may better organize cooperative transformations when the existing system becomes untenable.

Sliding clamps are ring-shaped oligomeric proteins that are essential for processive deoxyribonucleic acid replication. Although crystallographic structures of several clamps have been determined, much less is known about clamp structure and dynamics in solution. Here, we characterized the intrinsic solution stability and oligomerization dynamics of the homodimeric Escherichia coli β and the homotrimeric Saccharomyces cerevisiae proliferating cell nuclear antigen (PCNA) clamps using single-molecule approaches. We show that E. coli β is stable in solution as a closed ring at concentrations three orders of magnitude lower than PCNA. The trimeric structure of PCNA results in slow subunit association rates and is largely responsible for the lower solution stability. Despite this large difference, the intrinsic lifetimes of the rings differ by only one order of magnitude. Our results show that the longer lifetime of the E. coli β dimer is due to more prominent electrostatic interactions that stabilize the subunit interfaces.

Contemporary vaccine development relies less on empirical methods of vaccine construction, and now employs a powerful array of precise engineering strategies to construct immunogenic live vaccines. In this review, we will survey various engineering techniques used to create attenuated vaccines, with an emphasis on recent advances and insights. We will further explore the adaptation of attenuated strains to create multivalent vaccine platforms for immunization against multiple unrelated pathogens. These carrier vaccines are engineered to deliver sufficient levels of protective antigens to appropriate lymphoid inductive sites to elicit both carrier-specific and foreign antigen-specific immunity. Although many of these technologies were originally developed for use in Salmonella vaccines, application of the essential logic of these approaches will be extended to development of other enteric vaccines where possible. A central theme driving our discussion will stress that the ultimate success of an engineered vaccine rests on achieving the proper balance between attenuation and immunogenicity. Achieving this balance will avoid over-activation of inflammatory responses, which results in unacceptable reactogenicity, but will retain sufficient metabolic fitness to enable the live vaccine to reach deep tissue inductive sites and trigger protective immunity. The breadth of examples presented herein will clearly demonstrate that genetic engineering offers the potential for rapidly propelling vaccine development forward into novel applications and therapies which will significantly expand the role of vaccines in public health.