Embedding dimension gaps in sparse codes

We study the open and closed embedding dimensions of a convex 3-sparse code $\mathcal{FP}$, which records the intersection pattern of lines in the Fano plane. We show that the closed embedding dimension of $\mathcal{FP}$ is three, and the open embedding dimension is between four and six, providing the first example of a 3-sparse code with closed embedding dimension three and differing open and closed embedding dimensions. We also investigate codes whose canonical form is quadratic, i.e. ``degree two" codes. We show that such codes are realizable by axis-parallel boxes, generalizing a recent result of Zhou on inductively pierced codes. We pose several open questions regarding sparse and low-degree codes. In particular, we conjecture that the open embedding dimension of certain 3-sparse codes derived from Steiner triple systems grows to infinity.Comment: 16 pages, 8 figure

Morphology and Tensile Properties of Multigraft Copolymers with Regularly Spaced Tri-, Tetra-, and Hexafunctional Junction Points

The effect of chain architecture on the morphological and tensile properties of series of multigraft copolymers, with regularly spaced tri-, tetra-, and hexafunctional junction points, was investigated using transmission electron microscopy (TEM), small-angle X-ray scattering (SAXS), and tensile testing. The materials were synthesized by coupling difunctional polyisoprene (PI) spacers and living polystyrene (PS) branches, made by anionic polymerization, with chlorosilanes of different functionalities. Since the coupling process is a step-growth polymerization, yielding polydisperse products, fractionation was utilized to separate each material into three fractions (high, middle, and low molecular weight), each of low polydispersity. All three fractions have the same chain architecture on a per junction point basis but differ in the number of junction point units per molecule. By applying the constituting block copolymer concept, the physical behavior of these molecules was compared with current theories. It was found that morphological behavior of these graft copolymers can be predicted using theoretical approaches and is independent on the number of junction points. The number of the junction points, however, greatly influences the long-range order of microphase separation. Additionally, two new parameters for adjusting mechanical properties of multigraft copolymers were found in this investigation: (1) functionality of the graft copolymerstri-, tetra-, or hexafunctionals and (2) number of junction points per molecule. An increase in functionality causes a change in morphology, resulting in a high level of tensile strength for tetrafunctional (cylindrical) and hexafunctional (lamellae) multigraft copolymers, leading to about the twice the strength of the spherical trifunctional multigrafts of similar overall composition. Tetrafunctional multigraft copolymers show a surprisingly high strain at break, far exceeding that of commercial block copolymer thermoplastic elastomers (TPEs). Strain at break and tensile strength increase linearly with the number of junction points per molecule. Hysteresis experiments at about 300-900% deformation demonstrate that multifunctional multigraft copolymers have improved high elasticity as compared to commercial TPEs like Kraton or Styroflex

The role of sand lances (Ammodytes sp.) in the Northwest Atlantic ecosystem: a synthesis of current knowledge with implications for conservation and management

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Staudinger, M. D., Goyert, H., Suca, J. J., Coleman, K., Welch, L., Llopiz, J. K., Wiley, D., Altman, I., Applegate, A., Auster, P., Baumann, H., Beaty, J., Boelke, D., Kaufman, L., Loring, P., Moxley, J., Paton, S., Powers, K., Richardson, D., Robbins, J., Runge, J., Smith, B., Spiegel, C., & Steinmetz, H. The role of sand lances (Ammodytes sp.) in the Northwest Atlantic ecosystem: a synthesis of current knowledge with implications for conservation and management. Fish and Fisheries, 00, (2020): 1-34, doi:10.1111/faf.12445.The American sand lance (Ammodytes americanus, Ammodytidae) and the Northern sand lance (A. dubius, Ammodytidae) are small forage fishes that play an important functional role in the Northwest Atlantic Ocean (NWA). The NWA is a highly dynamic ecosystem currently facing increased risks from climate change, fishing and energy development. We need a better understanding of the biology, population dynamics and ecosystem role of Ammodytes to inform relevant management, climate adaptation and conservation efforts. To meet this need, we synthesized available data on the (a) life history, behaviour and distribution; (b) trophic ecology; (c) threats and vulnerabilities; and (d) ecosystem services role of Ammodytes in the NWA. Overall, 72 regional predators including 45 species of fishes, two squids, 16 seabirds and nine marine mammals were found to consume Ammodytes. Priority research needs identified during this effort include basic information on the patterns and drivers in abundance and distribution of Ammodytes, improved assessments of reproductive biology schedules and investigations of regional sensitivity and resilience to climate change, fishing and habitat disturbance. Food web studies are also needed to evaluate trophic linkages and to assess the consequences of inconsistent zooplankton prey and predator fields on energy flow within the NWA ecosystem. Synthesis results represent the first comprehensive assessment of Ammodytes in the NWA and are intended to inform new research and support regional ecosystem‐based management approaches.This manuscript is the result of follow‐up work stemming from a working group formed at a two‐day multidisciplinary and international workshop held at the Parker River National Wildlife Refuge, Massachusetts in May 2017, which convened 55 experts scientists, natural resource managers and conservation practitioners from 15 state, federal, academic and non‐governmental organizations with interest and expertise in Ammodytes ecology. Support for this effort was provided by USFWS, NOAA Stellwagen Bank National Marine Sanctuary, U.S. Department of the Interior, U.S. Geological Survey, Northeast Climate Adaptation Science Center (Award # G16AC00237), an NSF Graduate Research Fellowship to J.J.S., a CINAR Fellow Award to J.K.L. under Cooperative Agreement NA14OAR4320158, NSF award OCE‐1325451 to J.K.L., NSF award OCE‐1459087 to J.A.R, a Regional Sea Grant award to H.B. (RNE16‐CTHCE‐l), a National Marine Sanctuary Foundation award to P.J.A. (18‐08‐B‐196) and grants from the Mudge Foundation. The contents of this paper are the responsibility of the authors and do not necessarily represent the views of the National Oceanographic and Atmospheric Administration, U.S. Fish and Wildlife Service, New England Fishery Management Council and Mid‐Atlantic Fishery Management Council. This manuscript is submitted for publication with the understanding that the United States Government is authorized to reproduce and distribute reprints for Governmental purposes. Any use of trade, firm or product names is for descriptive purposes only and does not imply endorsement by the U.S. Government

COVID-19 and lessons from multi-hazard early warning systems

Having a common framework for early action to cope with complex disasters can make it easier for authorities and other stakeholders, including populations at risk, to understand the full spectrum of secondary and tertiary effects and thus where to focus preparedness efforts, and how best to provide more targeted warnings and response services. Meteorological and hydrological services world-wide have developed and implemented Multi-Hazard Early Warning Systems (MHEWS) for weather and climate related hazards that are now being expanded and transitioned towards Multi-Hazard Impact-based Early Warning Systems (MHIEWS). While it is still early days it is becoming clear that there are useful lessons from this approach in the COVID-19 global pandemic, and some valuable insight to be gained in risk communication, risk analysis and monitoring methodologies and approaches. The ability to understand and respond effectively to warnings through appropriate behaviours and actions is central to resilient societies and communities. By avoiding physical, societal and economic harm to the greatest extent possible, recovery from a hazard is likely to be faster, less costly and more complete. MHIEWS can be a common approach for all hazards and therefore more likely to become a trusted tool that everyone can understand and use as a basic element of their national disaster risk management system. The interconnectedness of hazards and their impacts is a strong motivator for a common approach. One of the lessons from the COVID-19 pandemic and extreme weather events is the need to understand the vulnerability of individuals, communities and societies so as to provide reliable, targeted guidance and warnings and the willingness and capacity to prepare for a reasonable worst-case scenario based on informed long-term planning. Meteorology and hydrology are making good progress in this direction and the process can be readily applied to health and other sectors

Morphological and dietary responses of chipmunks to a century of climate change.

Predicting how individual taxa will respond to climatic change is challenging, in part because the impacts of environmental conditions can vary markedly, even among closely related species. Studies of chipmunks (Tamias spp.) in Yosemite National Park provide an important opportunity to explore the reasons for this variation in response. While the alpine chipmunk (T. alpinus) has undergone a significant elevational range contraction over the past century, the congeneric and partially sympatric lodgepole chipmunk (T. speciosus) has not experienced an elevational range shift during this period. As a first step toward identifying the factors underlying this difference in response, we examined evidence for dietary changes and changes in cranial morphology in these species over the past century. Stable isotope analyses of fur samples from modern and historical museum specimens of these species collected at the same localities indicated that signatures of dietary change were more pronounced in T. alpinus, although diet breadth did not differ consistently between the study species. Morphometric analyses of crania from these specimens revealed significant changes in cranial shape for T. alpinus, with less pronounced changes in shape for T. speciosus; evidence of selection on skull morphology was detected for T. alpinus, but not for T. speciosus. These results are consistent with growing evidence that T. alpinus is generally more responsive to environmental change than T. speciosus, but emphasize the complex and often geographically variable nature of such responses. Accordingly, future studies that make use of the taxonomically and spatially integrative approach employed here may prove particularly informative regarding relationships between environmental conditions, range changes, and patterns of phenotypic variation

It's about time: A synthesis of changing phenology in the Gulf of Maine ecosystem

© The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Staudinger, M. D., Mills, K. E., Stamieszkin, K., Record, N. R., Hudak, C. A., Allyn, A., Diamond, A., Friedland, K. D., Golet, W., Henderson, M. E., Hernandez, C. M., Huntington, T. G., Ji, R., Johnson, C. L., Johnson, D. S., Jordaan, A., Kocik, J., Li, Y., Liebman, M., Nichols, O. C., Pendleton, D., Richards, R. A., Robben, T., Thomas, A. C., Walsh, H. J., & Yakola, K. It's about time: A synthesis of changing phenology in the Gulf of Maine ecosystem. Fisheries Oceanography, 28(5), (2019): 532-566, doi: 10.1111/fog.12429.The timing of recurring biological and seasonal environmental events is changing on a global scale relative to temperature and other climate drivers. This study considers the Gulf of Maine ecosystem, a region of high social and ecological importance in the Northwest Atlantic Ocean and synthesizes current knowledge of (a) key seasonal processes, patterns, and events; (b) direct evidence for shifts in timing; (c) implications of phenological responses for linked ecological‐human systems; and (d) potential phenology‐focused adaptation strategies and actions. Twenty studies demonstrated shifts in timing of regional marine organisms and seasonal environmental events. The most common response was earlier timing, observed in spring onset, spring and winter hydrology, zooplankton abundance, occurrence of several larval fishes, and diadromous fish migrations. Later timing was documented for fall onset, reproduction and fledging in Atlantic puffins, spring and fall phytoplankton blooms, and occurrence of additional larval fishes. Changes in event duration generally increased and were detected in zooplankton peak abundance, early life history periods of macro‐invertebrates, and lobster fishery landings. Reduced duration was observed in winter–spring ice‐affected stream flows. Two studies projected phenological changes, both finding diapause duration would decrease in zooplankton under future climate scenarios. Phenological responses were species‐specific and varied depending on the environmental driver, spatial, and temporal scales evaluated. Overall, a wide range of baseline phenology and relevant modeling studies exist, yet surprisingly few document long‐term shifts. Results reveal a need for increased emphasis on phenological shifts in the Gulf of Maine and identify opportunities for future research and consideration of phenological changes in adaptation efforts.This work was supported by the Department of the Interior Northeast Climate Adaptation Science Center (G14AC00441) for MDS, AJ, and KY; the National Science Foundation's Coastal SEES Program (OCE‐1325484) for KEM, ACT, MEH, and AA; the National Aeronautics and Space Administration (NNX16 AG59G) for ACT, KEM, NRR, and KSS; the USGS Climate Research and Development Program for TGH; National Science & Engineering Research Council of Canada, University of New Brunswick, Environment Canada, Sir James Dunn Wildlife Research Centre, and New Brunswick Wildlife Trust Fund for AD. We also thank the Regional Association for Research on the Gulf of Maine for support, and the Gulf of Maine Research Institute for hosting and providing in kind resources for a two day in‐person workshop in August 2016. We greatly appreciate contributions from K. Alexander, G. Calandrino, C. Feurt, I. Mlsna, N. Rebuck, J. Seavey, and J. Sun for helping shape the initial scope of the manuscript. We thank J. Weltzin and two anonymous reviewers for their constructive comments. The contents of this paper are solely the responsibility of the authors and do not necessarily represent the views of the Northeast Climate Adaptation Science Center, U.S. Geological Survey, National Oceanographic and Atmospheric Administration, Fisheries and Oceans Canada or the US Environmental Protection Agency. This manuscript is submitted for publication with the understanding that the United States Government is authorized to reproduce and distribute reprints for Governmental purposes. None of the authors have conflicts of interest to declare in association with the contents of this manuscript

Dupilumab shows long-term safety and efficacy in patients with moderate to severe atopic dermatitis enrolled in a phase 3 open-label extension study

BACKGROUND: Significant unmet need exists for long-term treatment of moderate to severe atopic dermatitis (AD). OBJECTIVE: To assess the long-term safety and efficacy of dupilumab in patients with AD. METHODS: This ongoing, multicenter, open-label extension study (NCT01949311) evaluated long-term dupilumab treatment in adults who had previously participated in phase 1 through 3 clinical trials of dupilumab for AD. This analysis examined patients given 300 mg dupilumab weekly for up to 76 weeks at data cutoff (April 2016). Safety was the primary outcome; efficacy was also evaluated. RESULTS: Of 1491 enrolled patients (1042.9 patient-years), 92.9% were receiving treatment at cutoff. The safety profile was consistent with previously reported trials (420.4 adverse events/100 patient-years and 8.5 serious adverse events/100 patient-years), with no new safety signals; common adverse events included nasopharyngitis, conjunctivitis, and injection-site reactions. Sustained improvement was seen up to 76 weeks in all efficacy outcomes, including measures of skin inflammation, pruritus, and quality of life. LIMITATIONS: Lack of control arm, limited number of patients with 76 weeks or longer of treatment (median follow-up, 24 weeks), and patients not receiving the approved dose regimen of 300 mg every 2 weeks. CONCLUSION: The safety and efficacy profile from this study supports the role of dupilumab as continuous long-term treatment for patients with moderate to severe AD

Pregnane X receptor regulates drug metabolism and transport in the vasculature and protects from oxidative stress

Aims Circulating endogenous, dietary and foreign chemicals can contribute to vascular dysfunction. The mechanism by which the vasculature protects itself from these chemicals is unknown. This study investigates whether the pregnane X receptor (PXR), the major transcriptional regulator of hepatic drug metabolism and transport that responds to such xenobiotics, mediates vascular protection by co-ordinating a defence gene program in the vasculature.Methods and Results PXR was detected in primary human and rat aortic endothelial and smooth muscle cells and blood vessels including human and rat aorta. Metabolic PXR target genes cytochrome P450 3A, 2B, 2C and glutathione-S-transferase mRNA and activity were induced by PXR ligands in rodent and human vascular cells and absent in the aortas from PXR null mice stimulated in vivo or in rat aortic smooth muscle cells expressing dominant negative PXR. Activation of aortic PXR by classical agonists had several protective effects; increased xenobiotic metabolism demonstrated by bio-activation of the pro-drug clopidogrel, which reduced adenosine diphosphate-induced platelet aggregation; increased expression of multidrug resistance protein 1, mediating chemical efflux from the vasculature; and protection from reactive oxygen species-mediated cell death.Conclusions PXR co-ordinately up-regulates drug metabolism, transport and anti-oxidant genes to protect the vasculature from endogenous and exogenous insults, thus representing a novel gatekeeper for vascular defence

Improved adherence with once-daily versus twice-daily dosing of mometasone furoate administered via a dry powder inhaler: a randomized open-label study

Background Poor adherence with prescribed asthma medication is a major barrier to positive treatment outcomes. This study was designed to determine the effect of a once-daily administration of mometasone furoate administered via a dry powder inhaler (MF-DPI) on treatment adherence compared with a twice-daily administration. Methods This was a 12-week open-label study designed to mimic an actual clinical setting in patients ≥12 years old with mild-to-moderate persistent asthma. Patients were randomized to receive MF-DPI 400 μg once-daily in the evening or MF-DPI 200 μg twice-daily. Adherence was assessed primarily using the number of actual administered doses reported from the device counter divided by the number of scheduled doses. Self-reports were also used to determine adherence. Health-related quality of life, healthcare resource utilization, and days missed from work or school were also reported. Results 1233 patients were randomized. The mean adherence rates, as measured by the automatic dose counter, were significantly better (P < 0.001) with MF-DPI 400 μg once-daily in the evening (93.3%) than with MF-DPI 200 μg twice-daily (89.5%). Mean adherence rates based on self-reports were also significantly better (P < 0.001) with MF-DPI 400 μg QD PM (97.2%) than with MF-DPI 200 μg twice-daily (95.3%). Adherence rates were lower in adolescents (12-17 years old). Health-related quality of life improved by 20% in patients using MF-DPI once-daily in the evening and by 14% in patients using MF-DPI twice-daily. Very few (<8%) patients missed work/school. Conclusion Mean adherence rates were greater with a once-daily dosing regimen of MF-DPI than with a twice-daily dosing regimen. This trial was completed prior to the ISMJE requirements for trial registration

Metabolism and Toxicity of Thioacetamide and Thioacetamide SOxide in Rat Hepatocytes

“This document is the Accepted Manuscript version of a Published Work that appeared in final form in Chemical Research in Toxicology, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/tx3002719The hepatotoxicity of thioacetamide (TA) has been known since 1948. In rats, single doses cause centrilobular necrosis accompanied by increases in plasma transaminases and bilirubin. To elicit these effects TA requires oxidative bioactivation leading first to its S-oxide (TASO) and then to its chemically reactive S,S-dioxide (TASO2) which ultimately modifies amine-lipids and proteins. To generate a suite of liver proteins adducted by TA metabolites for proteomic analysis, and to reduce the need for both animals and labeled compounds, we treated isolated hepatocytes directly with TA. Surprisingly, TA was not toxic at concentrations up to 50 mM for 40 hr. On the other hand, TASO was highly toxic to isolated hepatocytes as indicated by LDH release, cellular morphology and vital staining with Hoechst 33342/propidium iodide. TASO toxicity was partially blocked by the CYP2E1 inhibitors diallyl sulfide and 4-methylpyrazole, and was strongly inhibited by TA. Significantly, we found that hepatocytes produce TA from TASO relatively efficiently by back-reduction. The covalent binding of [14C]-TASO is inhibited by unlabeled TA which acts as a “cold-trap” for [14C]-TA and prevents its re-oxidation to [14C]-TASO. This in turn increases the net consumption of [14C]-TASO despite the fact that its oxidation to TASO2 is inhibited. The potent inhibition of TASO oxidation by TA, coupled with the back-reduction of TASO and its futile redox cycling with TA may help explain phenomena previously interpreted as “saturation toxicokinetics” in the in vivo metabolism and toxicity of TA and TASO. The improved understanding of the metabolism and covalent binding of TA and TASO facilitates the use of hepatocytes to prepare protein adducts for target protein identification