1,343 research outputs found
Increased Lysis of Stem Cells but Not Their Differentiated Cells by Natural Killer Cells; De-Differentiation or Reprogramming Activates NK Cells
The aims of this study are to demonstrate the increased lysis of stem cells but not their differentiated counterparts by the NK cells and to determine whether disturbance in cell differentiation is a cause for increased sensitivity to NK cell mediated cytotoxicity. Increased cytotoxicity and augmented secretion of IFN-Îł were both observed when PBMCs or NK cells were co-incubated with primary UCLA oral squamous carcinoma stem cells (UCLA-OSCSCs) when compared to differentiated UCLA oral squamous carcinoma cells (UCLA-OSCCs). In addition, human embryonic stem cells (hESCs) were also lysed greatly by the NK cells. Moreover, NK cells were found to lyse human Mesenchymal Stem Cells (hMSCs), human dental pulp stem cells (hDPSCs) and human induced pluripotent stem cells (hiPSCs) significantly more than their differentiated counterparts or parental lines from which they were derived. It was also found that inhibition of differentiation or reversion of cells to a less-differentiated phenotype by blocking NFÎșB or targeted knock down of COX2 in monocytes significantly augmented NK cell cytotoxicity and secretion of IFN-Îł. Taken together, these results suggest that stem cells are significant targets of the NK cell cytotoxicity. However, to support differentiation of a subset of tumor or healthy untransformed primary stem cells, NK cells may be required to lyse a number of stem cells and/or those which are either defective or incapable of full differentiation in order to lose their cytotoxic function and gain the ability to secrete cytokines (split anergy). Therefore, patients with cancer may benefit from repeated allogeneic NK cell transplantation for specific elimination of cancer stem cells
Solving the time-dependent Schr\"odinger equation with absorbing boundary conditions and source terms in Mathematica 6.0
In recent decades a lot of research has been done on the numerical solution
of the time-dependent Schr\"odinger equation. On the one hand, some of the
proposed numerical methods do not need any kind of matrix inversion, but source
terms cannot be easily implemented into this schemes; on the other, some
methods involving matrix inversion can implement source terms in a natural way,
but are not easy to implement into some computational software programs widely
used by non-experts in programming (e.g. Mathematica). We present a simple
method to solve the time-dependent Schr\"odinger equation by using a standard
Crank-Nicholson method together with a Cayley's form for the finite-difference
representation of evolution operator. Here, such standard numerical scheme has
been simplified by inverting analytically the matrix of the evolution operator
in position representation. The analytical inversion of the N x N matrix let us
easily and fully implement the numerical method, with or without source terms,
into Mathematica or even into any numerical computing language or computational
software used for scientific computing.Comment: 15 pages, 7 figure
Tritium labeling of potential lipophilic myelin probes
Two potential lipophilic myelin imaging agents (1,1,2,2âtetrafluoroâ1,2âdiphenylethane and 1âfluoroadamantane) were tritium labeled. The most effective method employed the microwave discharge activation of tritium gas technique and resulted in specific activities of 177 mCi/mmol for 1,1,2,2âtetrafluoroâ1,2âdiphenylethane and 593 mCi/mmol for 1âfluoroadamantane. Using this tritiation method significant amounts of tritiumâforâfluorine substitution was also observed in the labeling of 1âfluoroadamatane, resulting in nearly equivalent amounts of tritiated adamantane and fluoroadamantane.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90398/1/2580210110_ftp.pd
The Canadian Neuromuscular Disease Registry 2010-2019: A Decade of Facilitating Clinical Research Througha Nationwide, Pan-NeuromuscularDisease Registry
We report the recruitment activities and outcomes of a multi-disease neuromuscular patient registry in Canada. The Canadian Neuromuscular Disease Registry (CNDR) registers individuals across Canada with a confirmed diagnosis of a neuromuscular disease. Diagnosis and contact information are collected across all diseases and detailed prospective data is collected for 5 specific diseases: Amyotrophic Lateral Sclerosis (ALS), Duchenne Muscular Dystrophy (DMD), Myotonic Dystrophy (DM), Limb Girdle Muscular Dystrophy (LGMD), and Spinal Muscular Atrophy (SMA). Since 2010, the CNDR has registered 4306 patients (1154 pediatric and 3148 adult) with 91 different neuromuscular diagnoses and has facilitated 125 projects (73 academic, 3 not-for-profit, 3 government, and 46 commercial) using registry data. In conclusion, the CNDR is an effective and productive pan-neuromuscular registry that has successfully facilitated a substantial number of studies over the past 10 years
Extended surfaces modulate and can catalyze hydrophobic effects
Interfaces are a most common motif in complex systems. To understand how the
presence of interfaces affect hydrophobic phenomena, we use molecular
simulations and theory to study hydration of solutes at interfaces. The solutes
range in size from sub-nanometer to a few nanometers. The interfaces are
self-assembled monolayers with a range of chemistries, from hydrophilic to
hydrophobic. We show that the driving force for assembly in the vicinity of a
hydrophobic surface is weaker than that in bulk water, and decreases with
increasing temperature, in contrast to that in the bulk. We explain these
distinct features in terms of an interplay between interfacial fluctuations and
excluded volume effects---the physics encoded in Lum-Chandler-Weeks theory [J.
Phys. Chem. B 103, 4570--4577 (1999)]. Our results suggest a catalytic role for
hydrophobic interfaces in the unfolding of proteins, for example, in the
interior of chaperonins and in amyloid formation.Comment: 22 pages, 5 figure
The 21Na(p,gamma)22Mg Reaction and Oxygen-Neon Novae
The 21Na(p,gamma)22Mg reaction is expected to play an important role in the
nucleosynthesis of 22Na in Oxygen-Neon novae. The decay of 22Na leads to the
emission of a characteristic 1.275 MeV gamma-ray line. This report provides the
first direct measurement of the rate of this reaction using a radioactive 21Na
beam, and discusses its astrophysical implications. The energy of the important
state was measured to be E= 205.7 0.5 keV with a resonance
strength meV.Comment: Accepted for publication in Physical Review Letter
Microsecond folding dynamics of the F13W G29A mutant of the B domain of staphylococcal protein A by laser-induced temperature jump
The small size (58 residues) and simple structure of the B domain of staphylococcal protein A (BdpA) have led to this domain being a paradigm for theoretical studies of folding. Experimental studies of the folding of BdpA have been limited by the rapidity of its folding kinetics. We report the folding kinetics of a fluorescent mutant of BdpA (G29A F13W), named F13W*, using nanosecond laser-induced temperature jump experiments. Automation of the apparatus has permitted large data sets to be acquired that provide excellent signal-to-noise ratio over a wide range of experimental conditions. By measuring the temperature and denaturant dependence of equilibrium and kinetic data for F13W*, we show that thermodynamic modeling of multidimensional equilibrium and kinetic surfaces is a robust method that allows reliable extrapolation of rate constants to regions of the folding landscape not directly accessible experimentally. The results reveal that F13W* is the fastest-folding protein of its size studied to date, with a maximum folding rate constant at 0 M guanidinium chloride and 45°C of 249,000 (s-1). Assuming the single-exponential kinetics represent barrier-limited folding, these data limit the value for the preexponential factor for folding of this protein to at least â2 x 10(6) s(-1)
Technical Note: Method to correlate wholeâspecimen histopathology of radical prostatectomy with diagnostic MR imaging
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134778/1/mp1016.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134778/2/mp1016_am.pd
Folding of small proteins: A matter of geometry?
We review some of our recent results obtained within the scope of simple
lattice models and Monte Carlo simulations that illustrate the role of native
geometry in the folding kinetics of two state folders.Comment: To appear in Molecular Physic
- âŠ