Lower-rim ferrocenyl substituted calixarenes: new electrochemical sensors for anions

New ferrocene substituted calix[4 and 5]arenes have been prepared and the crystal structure of a lower-rim substituted bis ferrocene calix[4]arene (7) has been elucidated. The respective ferrocene/ferrocenium redox-couples of compounds 6 (a calix[4]arene tetra ferrocene amide) and 8 (a calix[5]arene pentaferrocene amide) are shown to be significantly cathodically perturbed in the presence of anions by up to 160 mV in the presence of dihydrogen phosphate

Vascular remodeling of the mouse yolk sac requires hemodynamic force

The embryonic heart and vessels are dynamic and form and remodel while functional. Much has been learned about the genetic mechanisms underlying the development of the cardiovascular system, but we are just beginning to understand how changes in heart and vessel structure are influenced by hemodynamic forces such as shear stress. Recent work has shown that vessel remodeling in the mouse yolk sac is secondarily effected when cardiac function is reduced or absent. These findings indicate that proper circulation is required for vessel remodeling, but have not defined whether the role of circulation is to provide mechanical cues, to deliver oxygen or to circulate signaling molecules. Here, we used time-lapse confocal microscopy to determine the role of fluid-derived forces in vessel remodeling in the developing murine yolk sac. Novel methods were used to characterize flows in normal embryos and in embryos with impaired contractility (Mlc2a^(–/–)). We found abnormal plasma and erythroblast circulation in these embryos, which led us to hypothesize that the entry of erythroblasts into circulation is a key event in triggering vessel remodeling. We tested this by sequestering erythroblasts in the blood islands, thereby lowering the hematocrit and reducing shear stress, and found that vessel remodeling and the expression of eNOS (Nos3) depends on erythroblast flow. Further, we rescued remodeling defects and eNOS expression in low-hematocrit embryos by restoring the viscosity of the blood. These data show that hemodynamic force is necessary and sufficient to induce vessel remodeling in the mammalian yolk sa

Perceptions of fecal microbiota transplantation for Clostridium difficile infection: factors that predict acceptance.

BackgroundDespite the effectiveness of fecal microbiota transplantation (FMT) for treating recurrent Clostridium difficile (C. difficile) infection, some patients are reluctant to accept this therapy. Our study examined attitudes towards FMT and factors that contribute to patients' acceptance of this treatment.MethodsWe distributed patient surveys at a Veterans Affairs hospital, a public hospital, and an academic faculty practice. Multivariable logistic regression was performed, adjusting for factors associated with FMT acceptance on univariate analysis and prior experience with C. difficile infection.ResultsOf 267 patients, only 12% knew of FMT prior to the survey, but 77% would undergo the procedure if medically indicated. On multivariable analysis, those with children and with college degrees or higher were more likely to agree to FMT (odds ratio [OR] 2.11, 95% confidence interval [CI] 1.02-4.35; OR 2.27, 95% CI 1.11-4.60 respectively). Sixty-five respondents (71%) chose colonoscopy as the preferred vehicle for FMT, while nasogastric tube was least preferred. Disease transmission was the most common concern (30%, n=242), and FMT success rate was the least selected concern (9.1%).ConclusionsMost patients in a diverse sample of gastroenterology clinics had no prior knowledge of FMT, but were receptive to the procedure. Having children and higher education levels were predictors for FMT acceptance. Our findings suggest that barriers to FMT utilization may be overcome with counseling about safety concerns. More data on the risk of transmitting diseases or clinical characteristics, such as obesity, through FMT are needed and will be important for the acceptance of this procedure

Solid Waste Disposal: Independent Food Service Practices

Solid waste disposal is a major concern today. This study seeks to identify the current practices and attitudes of managers of independent food services toward solid waste management and the characteristics of food services which were most likely to be involved with a solid waste management progra

Defect filtering for thermal expansion induced dislocations in III-V lasers on silicon

Epitaxially integrated III-V semiconductor lasers for silicon photonics have the potential to dramatically transform information networks, but currently, dislocations limit performance and reliability even in defect tolerant InAs quantum dot (QD) based lasers. Despite being below critical thickness, QD layers in these devices contain previously unexplained misfit dislocations, which facilitate non-radiative recombination. We demonstrate here that these misfit dislocations form during post-growth cooldown due to the combined effects of (1) thermal-expansion mismatch between the III-V layers and silicon and (2) precipitate and alloy hardening in the active region. By incorporating an additional sub-critical thickness, indium-alloyed misfit dislocation trapping layer, we leverage these mechanical hardening effects to our advantage, successfully displacing 95% of misfit dislocations from the QD layer in model structures. Unlike conventional dislocation mitigation strategies, the trapping layer reduces neither the number of threading dislocations nor the number of misfit dislocations. It simply shifts the position of misfit dislocations away from the QD layer, reducing the defects' impact on luminescence. In full lasers, adding a misfit dislocation trapping layer both above and below the QD active region displaces misfit dislocations and substantially improves performance: we measure a twofold reduction in lasing threshold currents and a greater than threefold increase in output power. Our results suggest that devices employing both traditional threading dislocation reduction techniques and optimized misfit dislocation trapping layers may finally lead to fully integrated, commercially viable silicon-based photonic integrated circuits.Comment: 9 pages, 6 figure

A preexisting rare PIK3CA e545k subpopulation confers clinical resistance to MEK plus CDK4/6 inhibition in NRAS melanoma and is dependent on S6K1 signaling

Combined MEK and CDK4/6 inhibition (MEKi + CDK4i) has shown promising clinical outcomes in patients with NRAS- mutant melanoma. Here, we interrogated longitudinal biopsies from a patient who initially responded to MEKi + CDK4i therapy but subsequently developed resistance. Whole-exome sequencing and functional validation identified an acquired PIK3CA E545K mutation as conferring drug resistance. We demonstrate that PIK3CA E545K preexisted in a rare subpopulation that was missed by both clinical and research testing, but was revealed upon multiregion sampling due to PIK3CA E545K being nonuniformly distributed. This resistant population rapidly expanded after the initiation of MEKi + CDK4i therapy and persisted in all successive samples even after immune checkpoint therapy and distant metastasis. Functional studies identified activated S6K1 as both a key marker and specific therapeutic vulnerability downstream of PIK3CA E545K -induced resistance. These results demonstrate that difficult-to-detect preexisting resistance mutations may exist more often than previously appreciated and also posit S6K1 as a common downstream therapeutic nexus for the MAPK, CDK4/6, and PI3K pathways. SIGNIFICANCE: We report the first characterization of clinical acquired resistance to MEKi + CDK4i, identifying a rare preexisting PIK3CA E545K subpopulation that expands upon therapy and exhibits drug resistance. We suggest that single-region pretreatment biopsy is insufficient to detect rare, spatially segregated drug-resistant subclones. Inhibition of S6K1 is able to resensitize PIK3CA E545K -expressing NRAS-mutant melanoma cells to MEKi + CDK4i. © 2018 AAC

Microplastic Contamination of Three Commonly Consumed Seafood Species from Taiwan: A Pilot Study

Microplastics have already been detected in various human foods, especially seafood. This problem should be especially pertinent to the Taiwanese public because a relatively high proportion of people’s diet comes from seafood. Therefore, a pilot study of microplastic contamination of seafood products commonly consumed by Taiwanese people is presented. Six batches of three seafood species were examined for the presence of microplastics using FTIR spectroscopy. A total of 107 seafood individuals from three species (hard clam Meretrix lusoria, oyster Crassostrea gigas, Loligo squid Loliginidae spp.) weighing a total of 994 g yielded a total of 100 microplastic particles consisting of nine different polymer types. The most common polymer types were polypropylene, poly(ethylene:propylene:diene), and polyethylene terephthalate; we also detected six additional, but less common polymer types. A total of 91% of microplastic particles were fragments that likely originated from fragmented plastic debris which was then consumed by the seafood species; the remaining particles were fibers and a pellet. The mean number of microplastics kg−1 was 87.9 microplastics kg−1 across the three examined species. Given that the Taiwanese public average about 10 kg of seafood consumption per year, a few thousand microplastic particles are estimated to be annually consumed on average. The methodology of this pilot study can now be used to conduct examinations of more seafood species and samples

Community-Derived Core Concepts for Neuroscience Higher Education

Core concepts provide a framework for organizing facts and understanding in neuroscience higher education curricula. Core concepts are overarching principles that identify patterns in neuroscience processes and phenomena and can be used as a foundational scaffold for neuroscience knowledge. The need for community-derived core concepts is pressing, because both the pace of research and number of neuroscience programs are rapidly expanding. While general biology and many subdisciplines within biology have identified core concepts, neuroscience has yet to establish a community-derived set of core concepts for neuroscience higher education. We used an empirical approach involving more than 100 neuroscience educators to identify a list of core concepts. The process of identifying neuroscience core concepts was modeled after the process used to develop physiology core concepts and involved a nationwide survey and a working session of 103 neuroscience educators. The iterative process identified eight core concepts and accompanying explanatory paragraphs. The eight core concepts are abbreviated as communication modalities, emergence, evolution, gene–environment interactions, information processing, nervous system functions, plasticity, and structure–function. Here, we describe the pedagogical research process used to establish core concepts for the neuroscience field and provide examples on how the core concepts can be embedded in neuroscience education