2,966 research outputs found

    Tactical reproductive parasitism via larval cannibalism in Peruvian poison frogs

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    We report an unusual example of reproductive parasitism in amphibians. Dendrobates variabi- lis, an Amazonian poison frog, oviposits at the surface of the water in small pools in plants and deposits tadpoles within the pools. Tadpoles are highly cannibalistic and consume young tadpoles if they are accessible. Deposition of embryos and tadpoles in the same pool is common. Genetic analyses indicate that tadpoles are fre- quently unrelated to embryos in the same pool. A pool choice experiment in the field demon- strated that males carrying tadpoles prefer to place them in pools with embryos, facilitating reproductive parasitism via cannibalism. Originally published Biology Letters, Vol. 5, No. 2, Apr 200

    A novel method for RNA extraction from FFPE samples reveals significant differences in biomarker expression between orthotopic and subcutaneous pancreatic cancer patient-derived xenografts.

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    Next-generation sequencing (NGS) can identify and validate new biomarkers of cancer onset, progression and therapy resistance. Substantial archives of formalin-fixed, paraffin-embedded (FFPE) cancer samples from patients represent a rich resource for linking molecular signatures to clinical data. However, performing NGS on FFPE samples is limited by poor RNA purification methods. To address this hurdle, we developed an improved methodology for extracting high-quality RNA from FFPE samples. By briefly integrating a newly-designed micro-homogenizing (mH) tool with commercially available FFPE RNA extraction protocols, RNA recovery is increased by approximately 3-fold while maintaining standard A260/A280 ratios and RNA quality index (RQI) values. Furthermore, we demonstrate that the mH-purified FFPE RNAs are longer and of higher integrity. Previous studies have suggested that pancreatic ductal adenocarcinoma (PDAC) gene expression signatures vary significantly under in vitro versus in vivo and in vivo subcutaneous versus orthotopic conditions. By using our improved mH-based method, we were able to preserve established expression patterns of KRas-dependency genes within these three unique microenvironments. Finally, expression analysis of novel biomarkers in KRas mutant PDAC samples revealed that PEAK1 decreases and MST1R increases by over 100-fold in orthotopic versus subcutaneous microenvironments. Interestingly, however, only PEAK1 levels remain elevated in orthotopically grown KRas wild-type PDAC cells. These results demonstrate the critical nature of the orthotopic tumor microenvironment when evaluating the clinical relevance of new biomarkers in cells or patient-derived samples. Furthermore, this new mH-based FFPE RNA extraction method has the potential to enhance and expand future FFPE-RNA-NGS cancer biomarker studies

    Forward and Inverse Modeling for Jovian Seismology

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    Jupiter is expected to pulsate in a spectrum of acoustic modes and recent re-analysis of a spectroscopic time series has identified a regular pattern in the spacing of the frequencies \citep{gaulme2011}. This exciting result can provide constraints on gross Jovian properties and warrants a more in-depth theoretical study of the seismic structure of Jupiter. With current instrumentation, such as the SYMPA instrument \citep{schmider2007} used for the \citet{gaulme2011} analysis, we assume that, at minimum, a set of global frequencies extending up to angular degree ℓ=25\ell=25 could be observed. In order to identify which modes would best constrain models of Jupiter's interior and thus help motivate the next generation of observations, we explore the sensitivity of derived parameters to this mode set. Three different models of the Jovian interior are computed and the theoretical pulsation spectrum from these models for ℓ≤25\ell\leq 25 is obtained. We compute sensitivity kernels and perform linear inversions to infer details of the expected discontinuities in the profiles in the Jovian interior. We find that the amplitude of the sound-speed jump of a few percent in the inner/outer envelope boundary seen in two of the applied models should be reasonably inferred with these particular modes. Near the core boundary where models predict large density discontinuities, the location of such features can be accurately measured, while their amplitudes have more uncertainty. These results suggest that this mode set would be sufficient to infer the radial location and strength of expected discontinuities in Jupiter's interior, and place strong constraints on the core size and mass. We encourage new observations to detect these Jovian oscillations.Comment: 31 pages, 12 figures, accepted to Icaru

    Hot topics, urgent priorities, and ensuring success for racial/ethnic minority young investigators in academic pediatrics.

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    BackgroundThe number of racial/ethnic minority children will exceed the number of white children in the USA by 2018. Although 38% of Americans are minorities, only 12% of pediatricians, 5% of medical-school faculty, and 3% of medical-school professors are minorities. Furthermore, only 5% of all R01 applications for National Institutes of Health grants are from African-American, Latino, and American Indian investigators. Prompted by the persistent lack of diversity in the pediatric and biomedical research workforces, the Academic Pediatric Association Research in Academic Pediatrics Initiative on Diversity (RAPID) was initiated in 2012. RAPID targets applicants who are members of an underrepresented minority group (URM), disabled, or from a socially, culturally, economically, or educationally disadvantaged background. The program, which consists of both a research project and career and leadership development activities, includes an annual career-development and leadership conference which is open to any resident, fellow, or junior faculty member from an URM, disabled, or disadvantaged background who is interested in a career in academic general pediatrics.MethodsAs part of the annual RAPID conference, a Hot Topic Session is held in which the young investigators spend several hours developing a list of hot topics on the most useful faculty and career-development issues. These hot topics are then posed in the form of six "burning questions" to the RAPID National Advisory Committee (comprised of accomplished, nationally recognized senior investigators who are seasoned mentors), the RAPID Director and Co-Director, and the keynote speaker.Results/conclusionsThe six compelling questions posed by the 10 young investigators-along with the responses of the senior conference leadership-provide a unique resource and "survival guide" for ensuring the academic success and optimal career development of young investigators in academic pediatrics from diverse backgrounds. A rich conversation ensued on the topics addressed, consisting of negotiating for protected research time, career trajectories as academic institutions move away from an emphasis on tenure-track positions, how "non-academic" products fit into career development, racism and discrimination in academic medicine and how to address them, coping with isolation as a minority faculty member, and how best to mentor the next generation of academic physicians

    New Test Rig to Measure Alternating Current Losses of Both Low and High Critical Temperature Superconductors

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    This paper presents the design, development, operation, and test capabilities of a proposed superconducting coil testbed to measure alternating current (AC) losses at the NASA Glenn Research Center. Superconducting AC losses are important in the design of electric stators and rotors, power transmission lines, transformers, fault current limiters, magnets, and superconducting energy storage (not batteries). The new liquid-hydrogen-based rig will allow superconducting testing across a wide range of test parameters, including injected current up to 400 A, frequency (0 to 400 Hz), magnetic field (0 to 0.6 T), phase angle between induced voltage and injected current (180 to 180), coil coolant temperature (18 to 28 K), and AC power loss (5 to 30 W). While the target application of interest is 20 K superconducting MgB2 (the only superconductor that can presently be made with low losses) stator coils for future electric machines, the rig can accommodate test articles (TAs) with straight wire, tape, cables, coils of any shape, any allowable combination of superconducting wire and fluid (e.g., yttrium barium copper oxide (YBCO) coils and liquid nitrogen), and AC or direct current (DC) testing. The new spin rig builds upon the existing Air Force spin rig through a more flexible mode of fluid control, a wider gap space (up to 10.2 cm) for TAs, and the ability to accommodate TAs over a wider range of operating temperatures (18 to 95 K) using liquid hydrogen, gaseous helium, or liquid nitrogen as the working fluid, thus supporting direct cooled machines below 77 K

    NK1.1 Expression Defines a Population of CD4+ Effector T Cells Displaying Th1 and Tfh Cell Properties That Support Early Antibody Production During Plasmodium yoelii Infection

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    Early plasmablast induction is a hallmark of Plasmodium infection and is thought to contribute to the control of acute parasite burden. Although long understood to be a T-cell dependent phenomenon, regulation of early plasmablast differentiation, however, is poorly understood. Here, we identify a population of CD4+ T cells that express the innate NK cell marker NK1.1 as an important source of T cell help for early plasmablast and parasite-specific Ab production. Interestingly, NK1.1+ CD4+ T cells arise from conventional, naive NK1.1− CD4+ T cells, and their generation is independent of CD1d but critically reliant on MHC-II. CD4+ T cells that express NK1.1 early after activation produce IFN-γ and IL-21, and express the follicular helper T (Tfh) cell markers ICOS, PD-1 and CXCR5 more frequently than NK1.1− CD4+ T cells. Further analysis of this population revealed that NK1.1+ Tfh-like cells were more regularly complexed with plasmablasts than NK1.1− Tfh-like cells. Ultimately, depletion of NK1.1+ cells impaired class-switched parasite-specific antibody production during early Plasmodium yoelii infection. Together, these data suggest that expression of NK1.1 defines a population of rapidly expanding effector CD4+ T cells that specifically promote plasmablast induction during Plasmodium infection and represent a subset of T cells whose modulation could promote effective vaccine design

    Preserving photon qubits in an unknown quantum state with Knill dynamical decoupling: Towards an all optical quantum memory

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    The implementation of polarization-based quantum communication is limited by signal loss and decoherence caused by the birefringence of a single-mode fiber. We investigate the Knill dynamical decoupling scheme, implemented using half-wave plates, to minimize decoherence and show that a fidelity greater than 99% can be achieved in absence of rotation error and fidelity greater than 96% can be achieved in presence of rotation error. Such a scheme can be used to preserve any quantum state with high fidelity and has potential application for constructing all optical quantum delay line, quantum memory, and quantum repeater

    In vitro bacterial vaginosis biofilm community manipulation using endolysin therapy

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    Bacterial vaginosis (BV) affects approximately 26% of women of childbearing age globally, presenting with 3–5 times increased risk of miscarriage and two-fold risk of pre-term birth. Antibiotics (metronidazole and clindamycin) are typically employed to treat BV; however the success rate is low due to the formation of recalcitrant polymicrobial biofilms. As a novel therapeutic, promising results have been obtained in vitro using Gardnerella endolysins, although to date their efficacy has only been demonstrated against simple biofilm models. In this study, a four-species biofilm was developed consisting of Gardnerella vaginalis, Fannyhessea vaginae, Prevotella bivia and Mobiluncus curtisii. Biofilms were grown in NYC III broth and treated using antibiotics and an anti-Gardnerella endolysin (CCB7.1) for 24 h. Biofilm composition, viability and structure were assessed using colony counts, live/dead qPCR and scanning electron microscopy. All species colonised biofilms to varying degrees, with G. vaginalis being the most abundant. Biofilm composition remained largely unchanged when challenged with escalated concentrations of conventional antibiotics. A Gardnerella-targeted endolysin candidate (CCB7.1) showed efficacy against several Gardnerella species planktonically, and significantly reduced viable G. vaginalis within polymicrobial biofilms at 1 to 4X pMIC (p < 0.05 vs. vehicle control). Collectively, this study highlights the resilience of biofilm-embedded pathogens against the currently used antibiotics and provides a polymicrobial model that allows for more effective pre-clinical screening of BV therapies. The Gardnerella-specific endolysin CCB7.1 demonstrated significant activity against G. vaginalis within polymicrobial biofilms, altering the overall community dynamic and composition
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