Microfluidic liquid sheets as large-area targets for high repetition XFELs

The high intensity of X-ray free electron lasers (XFELs) can damage solution-phase samples on every scale, ranging from the molecular or electronic structure of a sample to the macroscopic structure of a liquid microjet. By using a large surface area liquid sheet microjet as a sample target instead of a standard cylindrical microjet, the incident X-ray spot size can be increased such that the incident intensity falls below the damage threshold. This capability is becoming particularly important for high repetition rate XFELs, where destroying a target with each pulse would require prohibitively large volumes of sample. We present here a study of microfluidic liquid sheet dimensions as a function of liquid flow rate. Sheet lengths, widths and thickness gradients are shown for three styles of nozzles fabricated from isotropically etched glass. In-vacuum operation and sample recirculation using these nozzles is demonstrated. The effects of intense XFEL pulses on the structure of a liquid sheet are also briefly examined

Empirically derived guidance for social scientists to influence environmental policy

Failure to stem trends of ecological disruption and associated loss of ecosystem services worldwide is partly due to the inadequate integration of the human dimension into environmental decision-making. Decision-makers need knowledge of the human dimension of resource systems and of the social consequences of decision-making if environmental management is to be effective and adaptive. Social scientists have a central role to play, but little guidance exists to help them influence decision-making processes. We distil 348 years of cumulative experience shared by 31 environmental experts across three continents into advice for social scientists seeking to increase their influence in the environmental policy arena. Results focus on the importance of process, engagement, empathy and acumen and reveal the importance of understanding and actively participating in policy processes through co-producing knowledge and building trust. The insights gained during this research might empower a science-driven cultural change in science-policy relations for the routine integration of the human dimension in environmental decision making; ultimately for an improved outlook for earth’s ecosystems and the billions of people that depend on them

Structure retrieval in liquid-phase electron scattering

Electron scattering on liquid samples has been enabled recently by the development of ultrathin liquid sheet technologies. The data treatment of liquid-phase electron scattering has been mostly reliant on methodologies developed for gas electron diffraction, in which theoretical inputs and empirical fittings are often needed to account for the atomic form factor and remove the inelastic scattering background. In this work, we present an alternative data treatment method that is able to retrieve the radial distribution of all the charged particle pairs without the need of either theoretical inputs or empirical fittings. The merits of this new method are illustrated through the retrieval of real-space molecular structure from experimental electron scattering patterns of liquid water, carbon tetrachloride, chloroform, and dichloromethane. Shown here is the arXiv version

Metagenetic Analysis of the Pregnant Microbiome in Horses

Placentitis is the leading cause of infectious abortion in the horse. Additionally, it can result in weak and/or growth restricted offspring. While the etiology of ascending placentitis is well described in mares, less is known regarding the pathogenesis of other types, such as nocardioform placentitis. This study aims to identify the microbial communities in different body sites of the pregnant mare in early gestation to establish a core microbiome that may be perturbed in pathologic pregnancies such as placentitis. We hypothesize that the equine placenta harbors a distinct resident microbiome in early pregnancy when characterized by metagenetics and that there will be a disparity in bacterial communities from the oral, vaginal, and fecal microbiome. Samples were collected from the oral cavity, vagina, anus, and the allantoic portion of the allantochorion (“placenta”) from five pregnant mares between 96 and 120 days of gestation. The V4 region of the 16S rRNA gene was amplified for Illumina MiSeq sequencing to examine core bacterial communities present in the different body sites. Microbial community composition of the pregnant ponies by body site was significantly different (Bray–Curtis dissimilarity). The placenta was significantly different from the feces, oral cavity, and vagina. Alpha diversity measuring the Shannon diversity matrix was significant, with the body sites being a compounding variable, meaning there was a difference in richness and evenness in the different microbial communities. Feces had the greatest alpha diversity, while the oral cavity and placenta similarly had the least. In conclusion, metagenetics did reveal distinct community differences in the oral, fecal, vaginal, and placenta cavities of the horse. The equine placenta does show similarities in its microbial communities to the oral cavity. Further research needs to be completed to investigate how bacteria may be translocated to the placenta from these other body sites and how they contribute to the development of placentitis

DataSheet1_Microfluidic liquid sheets as large-area targets for high repetition XFELs.PDF

The high intensity of X-ray free electron lasers (XFELs) can damage solution-phase samples on every scale, ranging from the molecular or electronic structure of a sample to the macroscopic structure of a liquid microjet. By using a large surface area liquid sheet microjet as a sample target instead of a standard cylindrical microjet, the incident X-ray spot size can be increased such that the incident intensity falls below the damage threshold. This capability is becoming particularly important for high repetition rate XFELs, where destroying a target with each pulse would require prohibitively large volumes of sample. We present here a study of microfluidic liquid sheet dimensions as a function of liquid flow rate. Sheet lengths, widths and thickness gradients are shown for three styles of nozzles fabricated from isotropically etched glass. In-vacuum operation and sample recirculation using these nozzles is demonstrated. The effects of intense XFEL pulses on the structure of a liquid sheet are also briefly examined.</p

Synthesis and Biological Evaluation of Indolyl-Pyridinyl-Propenones Having Either Methuosis or Microtubule Disruption Activity

Methuosis is a form of nonapoptotic cell death characterized by an accumulation of macropinosome-derived vacuoles with eventual loss of membrane integrity. Small molecules inducing methuosis could offer significant advantages compared to more traditional anticancer drug therapies that typically rely on apoptosis. Herein we further define the effects of chemical substitutions at the 2- and 5-indolyl positions on our lead compound 3-(5-methoxy-2-methyl-1<i>H</i>-indol-3-yl)-1-(4-pyridinyl)-2-propene-1-one (MOMIPP). We have identified a number of compounds that induce methuosis at similar potencies, including an interesting analogue having a hydroxypropyl substituent at the 2-position. In addition, we have discovered that certain substitutions on the 2-indolyl position redirect the mode of cytotoxicity from methuosis to microtubule disruption. This switch in activity is associated with an increase in potency as large as 2 orders of magnitude. These compounds appear to represent a new class of potent microtubule-active anticancer agents

Synthesis and Biological Evaluation of Indolyl-Pyridinyl-Propenones Having Either Methuosis or Microtubule Disruption Activity

Methuosis is a form of nonapoptotic cell death characterized by an accumulation of macropinosome-derived vacuoles with eventual loss of membrane integrity. Small molecules inducing methuosis could offer significant advantages compared to more traditional anticancer drug therapies that typically rely on apoptosis. Herein we further define the effects of chemical substitutions at the 2- and 5-indolyl positions on our lead compound 3-(5-methoxy-2-methyl-1<i>H</i>-indol-3-yl)-1-(4-pyridinyl)-2-propene-1-one (MOMIPP). We have identified a number of compounds that induce methuosis at similar potencies, including an interesting analogue having a hydroxypropyl substituent at the 2-position. In addition, we have discovered that certain substitutions on the 2-indolyl position redirect the mode of cytotoxicity from methuosis to microtubule disruption. This switch in activity is associated with an increase in potency as large as 2 orders of magnitude. These compounds appear to represent a new class of potent microtubule-active anticancer agents