A Pyrrole-Based Triazolium-Phane with Nh and Cationic Ch Donor Groups as a Receptor for Tetrahedral Oxyanions that Functions in Polar Media

The pyrrole-based triazolium-phane 1(4+)center dot 4BF(4)(-) has been prepared via the tetraalkylation of a macrocycle originally prepared via click chemistry. It displays a high selectivity for tetrahedral oxyanions relative to various test monoanions and trigonal planar anions in mixed polar organic-aqueous media. This selectivity is solvent dependent and is less pronounced in acetonitrile. Theoretical calculations were carried out in with the chloride anion in an effort to understand the influence of solvent on the intrinsic hydrogen bonding ability of the donor groups (pyrrole N-H, benzene C-H and triazolium C-H). The host-guest interactions between receptor 1(4+)center dot 4BF(4)(-) and representative tetrahedral oxyanions were further analysed by H-1 NMR spectroscopy, and the findings proved consistent with the differences in the intrinsic strength of the various H-bond donor groups inferred from the electronic structure calculations carried out in methanol, namely that (CH)(+)-anion interactions are less important in an energetic sense than neutral CH-anion interactions in polar media. Single crystal X-ray diffraction analyses of the mixed salts 1(4+)center dot HP2O73-center dot BF4- and 31(4+)center dot 4H(2)PO(4)(-)center dot 8BF(4)(-) confirmed that receptor 1(4+) can bind the pyrophosphate and phosphate anions in the solid state.Cai, Jiajia, Benjamin P. Hay, Neil J. Young, Xiaoping Yang, and Jonathan L. Sessler. "A pyrrole-based triazolium-phane with NH and cationic CH donor groups as a receptor for tetrahedral oxyanions that functions in polar media." Chemical Science 4, no. 4 (Jan., 2013): 1560-1567.Chemistr

Distinguishing the “Truly National” From the “Truly Local”: Customary Allocation, Commercial Activity, and Collective Action

This Essay makes two claims about different methods of defining the expanse and limits of the Commerce Clause. My first claim is that approaches that privilege traditional subjects of state regulation are unworkable and undesirable. These approaches are unworkable in light of the frequency with which the federal government and the states regulate the same subject matter in our world of largely overlapping federal and state legislative jurisdiction. The approaches are undesirable because the question of customary allocation is unrelated to the principal reason why Congress possesses the power to regulate interstate commerce: solving collective action problems involving multiple states. These problems are evident in the way that some federal judges invoked regulatory custom in litigation over the constitutionality of the minimum coverage provision in the Patient Protection and Affordable Care Act. The areas of health insurance and health care are not of exclusive state concern, and it is impossible to lose—or to win—a competition requiring skillful lawyers or judges to describe them as more state than federal, or more federal than state. Nor is it most important what the answer is. More promising are the approaches that view congressional authority as turning on either commercial activity or collective action problems facing the states. My second claim is that these two approaches have advantages and disadvantages, and that the choice between them exemplifies the more general tension between applying rules and applying their background justifications. I have previously defended a collective action approach to Article I, Section 8. My primary purpose in this Essay is to clarify the jurisprudential stakes in adopting one method or the other and to identify the problems that advocates of each approach must address

Stirring and mixing : 1999 Program of Summer Study in Geophysical Fluid Dynamics

The central theme of the 1999 GFD Program was the stirring, transport, reaction and mixing of passive and active tracers in turbulent, stratified, rotating fluids. The problem of mixing in fluids has applications in areas ranging from oceanography to engineering and astrophysics. In geophysical settings, mixing spans and unites a broad range of scales -- from micrometers to megameters. The mixing of passive tracers is of fundamental importance in environmental and industrial problems, such as pollution, and in determining the large-scale heat and salt balance of the worlds oceans. The transport of active tracers, on the other hand, such as vorticity, plays a key role in the turbulence that occurs in most geophysical and astrophysical fluids. William R. Young (Scripps Institution of Oceanography) gave a series of principal lectures, the notes of which as taken by the fellows, appear in this volume. Report of the projects of the student fellows makes up the second half of this volume.Funding was provided by the National Science Foundation under Grant No. OCE-9810647 and the Office of Naval Research under Grant No. NOO0l4-97-1-0934

Hsc70-induced changes in clathrin-auxilin cage structure suggest a role for clathrin light chains in cage disassembly

The molecular chaperone, Hsc70, together with its co-factor, auxilin, facilitates the ATP-dependent removal of clathrin during clathrin-mediated endocytosis in cells. We have used cryo-electron microscopy to determine the 3D structure of a complex of clathrin, auxilin401-910 and Hsc70 at pH 6 in the presence of ATP, frozen within 20 seconds of adding Hsc70 in order to visualize events that follow the binding of Hsc70 to clathrin and auxilin before clathrin disassembly. In this map, we observe density beneath the vertex of the cage that we attribute to bound Hsc70. This density emerges asymmetrically from the clathrin vertex, suggesting preferential binding by Hsc70 for one of the three possible sites at the vertex. Statistical comparison with a map of whole auxilin and clathrin previously published by us reveals the location of statistically significant differences which implicate involvement of clathrin light chains in structural rearrangements which occur after Hsc70 is recruited. Clathrin disassembly assays using light scattering suggest that loss of clathrin light chains reduces the efficiency with which auxilin facilitates this reaction. These data support a regulatory role for clathrin light chains in clathrin disassembly in addition to their established role in regulating clathrin assembly

The response of soil microbial diversity and abundance to long-term application of biosolids

The disposal of biosolids poses a major environmental and economic problem. Agricultural use is generally regarded as the best means of disposal. However, its impact on soil ecosystems remains uncertain. Biosolids can improve soil properties by supplying nutrients and increasing organic matter content but there is also a potentially detrimental effect arising from the introduction of heavy metals into soils. To assess the balance between these competing effects on soil health, we investigated soil bacterial and fungal diversity and community structure at a site that has been dedicated to the disposal of sewage sludge for over 100 years. Terminal restriction fragment length polymorphism (T-RFLP) was used to characterize the soil microbial communities. The most important contaminants at the site were Ni, Cu, Zn, Cd, and Pb. Concentrations were highly correlated and Zn concentration was adopted as a good indicator of the overall (historical) biosolids loading. A biosolids loading, equivalent to 700–1000 mg kg−1 Zn appeared to be optimal for maximum bacterial and fungal diversity. This markedly exceeds the maximum soil Zn concentration of 300 mg kg−1permitted under the current UK Sludge (use in agriculture) Regulations. Redundancy analysis (RDA) suggested that the soil microbial communities had been altered in response to the accumulation of trace metals, especially Zn, Cd, and Cu. We believe this is the first time the trade-off between positive and negative effects of long term (>100 years) biosolids disposal on soil microorganisms have been observed in the field situation

Disease Knowledge Transfer across Neurodegenerative Diseases

We introduce Disease Knowledge Transfer (DKT), a novel technique for transferring biomarker information between related neurodegenerative diseases. DKT infers robust multimodal biomarker trajectories in rare neurodegenerative diseases even when only limited, unimodal data is available, by transferring information from larger multimodal datasets from common neurodegenerative diseases. DKT is a joint-disease generative model of biomarker progressions, which exploits biomarker relationships that are shared across diseases. Our proposed method allows, for the first time, the estimation of plausible, multimodal biomarker trajectories in Posterior Cortical Atrophy (PCA), a rare neurodegenerative disease where only unimodal MRI data is available. For this we train DKT on a combined dataset containing subjects with two distinct diseases and sizes of data available: 1) a larger, multimodal typical AD (tAD) dataset from the TADPOLE Challenge, and 2) a smaller unimodal Posterior Cortical Atrophy (PCA) dataset from the Dementia Research Centre (DRC), for which only a limited number of Magnetic Resonance Imaging (MRI) scans are available. Although validation is challenging due to lack of data in PCA, we validate DKT on synthetic data and two patient datasets (TADPOLE and PCA cohorts), showing it can estimate the ground truth parameters in the simulation and predict unseen biomarkers on the two patient datasets. While we demonstrated DKT on Alzheimer's variants, we note DKT is generalisable to other forms of related neurodegenerative diseases. Source code for DKT is available online: https://github.com/mrazvan22/dkt.Comment: accepted at MICCAI 2019, 13 pages, 5 figures, 2 table

Impact and Experiences Relative to Critical Incidents and Critical Incident Stress Management

Purpose: Typically, athletic trainers (ATs) have relied on external support networks to debrief after a critical incident (CI). ATs report focusing on improving work-related processes after a CI rather than their emotional response to the CI. The purpose of this study was to identify both the short-term emotional impacts of CIs and what coping strategies ATs use to address their emotional response to CIs. Methods: We used a cross-sectional, web-based survey, distributed to a random sample of NATA members to explore the perceived effects of CIs on ATs. Participants (n=73, 36±11y) were primarily women (n=53, 72.6%), working in the college/university practice setting (n = 40, 54.8%), with 7±3y of experience. All participants experienced a CI within the previous 12 months. The data were analyzed using descriptive statistics for demographic variables and multi-analyst inductive coding for the open-ended items amongst a 4-person team. We used a modified consensual qualitative research (CQR) process to review and analyze the open-ended questions and identify domains and core ideas. Trustworthiness was established with multi-analyst triangulation and auditing. Results: Participants most commonly reported feelings of thinking too much (71%, n=52), anxiety (63%, n=46), sadness (60%, n=44), fatigue (53%, n=39), and sleep disturbance (49%, n=36) resulting from CIs. Common coping strategies used were exercise (63%, n=46), humor (44%, n=32), interacting with pets (41%, n=30), expressing oneself through crying (40%, n=29), and peer support (34%, n=25). Sixty-two participants (86%) responded to open-ended questions related to the outcomes of CIs. Four domains were identified from the open-ended responses. Those domains included 1) dissociation, 2) deteriorated emotional state, 3) disruption of daily activities, and 4) improved event or post-event processes. Conclusion: Various strategies are used by ATs to cope with CIs; however, the only ways in which ATs expressed that coping helped was with care delivery, not the emotional impact of the CI. The lack of responses relative to coping strategies that improve quality of life is potentially alarming. To build resilience and persistence, organizations should consider requiring support beyond process improvement that addresses the emotional impact of CIs

Biocompatibility and Physiological Thiolytic Degradability of Radically Made Thioester-Functional Copolymers: Opportunities for Drug Release

Being nondegradable, vinyl polymers have limited biomedical applicability. Unfortunately, backbone esters incorporated through conventional radical ring-opening methods do not undergo appreciable abiotic hydrolysis under physiologically relevant conditions. Here, PEG acrylate and di(ethylene glycol) acrylamide-based copolymers containing backbone thioesters were prepared through the radical ring-opening copolymerization of the thionolactone dibenzo[c,e]oxepin-5(7H)-thione. The thioesters degraded fully in the presence of 10 mM cysteine at pH 7.4, with the mechanism presumed to involve an irreversible S–N switch. Degradations with N-acetylcysteine and glutathione were reversible through the thiol–thioester exchange polycondensation of R–SC(═O)–polymer–SH fragments with full degradation relying on an increased thiolate/thioester ratio. Treatment with 10 mM glutathione at pH 7.2 (mimicking intracellular conditions) triggered an insoluble–soluble switch of a temperature-responsive copolymer at 37 °C and the release of encapsulated Nile Red (as a drug model) from core-degradable diblock copolymer micelles. Copolymers and their cysteinolytic degradation products were found to be noncytotoxic, making thioester backbone-functional polymers promising for drug delivery applications