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Highly efficient transfection of human induced pluripotent stem cells using magnetic nanoparticles.
PurposeThe delivery of transgenes into human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (hiPSC-CMs) represents an important tool in cardiac regeneration with potential for clinical applications. Gene transfection is more difficult, however, for hiPSCs and hiPSC-CMs than for somatic cells. Despite improvements in transfection and transduction, the efficiency, cytotoxicity, safety, and cost of these methods remain unsatisfactory. The objective of this study is to examine gene transfection in hiPSCs and hiPSC-CMs using magnetic nanoparticles (NPs).MethodsMagnetic NPs are unique transfection reagents that form complexes with nucleic acids by ionic interaction. The particles, loaded with nucleic acids, can be guided by a magnetic field to allow their concentration onto the surface of the cell membrane. Subsequent uptake of the loaded particles by the cells allows for high efficiency transfection of the cells with nucleic acids. We developed a new method using magnetic NPs to transfect hiPSCs and hiPSC-CMs. HiPSCs and hiPSC-CMs were cultured and analyzed using confocal microscopy, flow cytometry, and patch clamp recordings to quantify the transfection efficiency and cellular function.ResultsWe compared the transfection efficiency of hiPSCs with that of human embryonic kidney (HEK 293) cells. We observed that the average efficiency in hiPSCs was 43%±2% compared to 62%±4% in HEK 293 cells. Further analysis of the transfected hiPSCs showed that the differentiation of hiPSCs to hiPSC-CMs was not altered by NPs. Finally, robust transfection of hiPSC-CMs with an efficiency of 18%±2% was obtained.ConclusionThe difficult-to-transfect hiPSCs and hiPSC-CMs were efficiently transfected using magnetic NPs. Our study offers a novel approach for transfection of hiPSCs and hiPSC-CMs without the need for viral vector generation
Intermediate Tail Dependence: A Review and Some New Results
The concept of intermediate tail dependence is useful if one wants to
quantify the degree of positive dependence in the tails when there is no strong
evidence of presence of the usual tail dependence. We first review existing
studies on intermediate tail dependence, and then we report new results to
supplement the review. Intermediate tail dependence for elliptical, extreme
value and Archimedean copulas are reviewed and further studied, respectively.
For Archimedean copulas, we not only consider the frailty model but also the
recently studied scale mixture model; for the latter, conditions leading to
upper intermediate tail dependence are presented, and it provides a useful way
to simulate copulas with desirable intermediate tail dependence structures.Comment: 25 pages, 1 figur
RICE Limits on the Diffuse Ultra-High Energy Neutrino Flux
We present new limits on ultra-high energy neutrino fluxes above 100 PeV
based on data collected by the Radio Ice Cherenkov Experiment (RICE) at the
South Pole from 1999-2005. We discuss estimation of backgrounds, calibration
and data analysis algorithms (both on-line and off-line), procedures used for
the dedicated neutrino search, and refinements in our Monte Carlo (MC)
simulation, including recent in situ measurements of the complex ice dielectric
constant. An enlarged data set and a more detailed study of hadronic showers
results in a sensitivity improvement of more than one order of magnitude
compared to our previously published results. Examination of the full RICE data
set yields zero acceptable neutrino candidates, resulting in 95%
confidence-level model dependent limits on the flux
(E_\nu)^2(d\phi/dE_\nu)<10^{-6} GeV/(cm^2s~sr}) in the energy range 10^{17}<
E_\nu< 10^{20} eV. The new RICE results rule out the most intense flux model
projections at 95% confidence level.Comment: Submitted to Astropart. Phy
Legacy of COVIDâ19 â the opportunity to enhance surgical services for patients with colorectal disease
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Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses
The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined
The \u3cem\u3eChlamydomonas\u3c/em\u3e Genome Reveals the Evolution of Key Animal and Plant Functions
Chlamydomonas reinhardtii is a unicellular green alga whose lineage diverged from land plants over 1 billion years ago. It is a model system for studying chloroplast-based photosynthesis, as well as the structure, assembly, and function of eukaryotic flagella (cilia), which were inherited from the common ancestor of plants and animals, but lost in land plants. We sequenced the âŒ120-megabase nuclear genome of Chlamydomonas and performed comparative phylogenomic analyses, identifying genes encoding uncharacterized proteins that are likely associated with the function and biogenesis of chloroplasts or eukaryotic flagella. Analyses of the Chlamydomonas genome advance our understanding of the ancestral eukaryotic cell, reveal previously unknown genes associated with photosynthetic and flagellar functions, and establish links between ciliopathy and the composition and function of flagella
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