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1.
Nat Biotechnol ; 28(6): 606-10, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20512120

ABSTRACT

Human embryonic stem cells (hESCs) have two properties of interest for the development of cell therapies: self-renewal and the potential to differentiate into all major lineages of somatic cells in the human body. Widespread clinical application of hESC-derived cells will require culture methods that are low-cost, robust, scalable and use chemically defined raw materials. Here we describe synthetic peptide-acrylate surfaces (PAS) that support self-renewal of hESCs in chemically defined, xeno-free medium. H1 and H7 hESCs were successfully maintained on PAS for over ten passages. Cell morphology and phenotypic marker expression were similar for cells cultured on PAS or Matrigel. Cells on PAS retained normal karyotype and pluripotency and were able to differentiate to functional cardiomyocytes on PAS. Finally, PAS were scaled up to large culture-vessel formats. Synthetic, xeno-free, scalable surfaces that support the self-renewal and differentiation of hESCs will be useful for both research purposes and development of cell therapies.


Subject(s)
Acrylates/pharmacology , Cell Culture Techniques/methods , Cell Differentiation/drug effects , Embryonic Stem Cells/cytology , Embryonic Stem Cells/drug effects , Myocytes, Cardiac/cytology , Peptides/pharmacology , Amino Acid Sequence , Animals , Cell Proliferation/drug effects , Humans , Mice , Molecular Sequence Data , Myocytes, Cardiac/drug effects , Peptides/chemistry , Surface Properties/drug effects , Time Factors
2.
J Cardiovasc Transl Res ; 2(2): 168-72, 2009 Jun.
Article in English | MEDLINE | ID: mdl-20559984

ABSTRACT

Impella 2.5 (Abiomed Inc., Danvers, Ma.) is a percutaneous microaxial circulatory support pump that delivers up to 2.5 l/min of systemic flow augmentation by pumping directly from the left ventricle into the ascending aorta. This article describes the device including the insertion method, fundamental principles of action, and clinical results from the completed Protect I clinical trial as well as general use under FDA clearance.


Subject(s)
Heart Failure/therapy , Heart-Assist Devices , Animals , Controlled Clinical Trials as Topic , Device Approval , Equipment Design , Evidence-Based Medicine , Heart Failure/physiopathology , Hemodynamics , Humans , Practice Guidelines as Topic , Treatment Outcome , United States , Ventricular Function, Left
3.
Rapid Commun Mass Spectrom ; 19(14): 2045-54, 2005.
Article in English | MEDLINE | ID: mdl-15988721

ABSTRACT

In vacuo trimethylation of the N-terminus of a lyophilized peptide with methyl iodide was previously reported to enhance the peptide's signal in matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and to suppress alkali adduct formation in electrospray ionization mass spectrometry (ESI-MS). Both the signal enhancement and alkali adduct suppression observed for methylated peptides are believed to be due to the permanent positive charge on the N-terminus of the peptide resulting from the formation of a quaternary ammonium moiety. The present work evaluates the general utility of the in vacuo methylation procedure for the MS analysis of peptides, and specifically addresses the issue of whether the methylation of nucleophilic sites other than the N-terminal amine affects the MALDI signal of modified peptides. This work establishes that, although certain side-chain modifications are inevitable using present reaction conditions, the derivatization leads to significant MALDI-MS signal improvement. The experimental results demonstrate that the N-terminal trimethylammonium derivatives of peptides exhibit MALDI signals comparable to or exceeding those of arginine-containing standards such as angiotensin I. The advantages and limitations of the in vacuo methylation procedure are discussed.


Subject(s)
Peptides/analysis , Peptides/chemistry , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Amino Acid Sequence , Angiotensin I/analysis , Angiotensin I/chemistry , Methylation
4.
Neural Netw ; 11(5): 837-850, 1998 Jul.
Article in English | MEDLINE | ID: mdl-12662786

ABSTRACT

We present a new neural network for detection and classification problems that is capable of creating spherical, elliptical, hyperbolic and linear decision surfaces. This new classifier is called the extended piecewise quadratic neural network (E-PQNN) and uses complex-valued weights and a square-law non-linearity. We prove that our simple E-PQNN architecture is able to generate piecewise quadratic decision surfaces of arbitrary rank and we develop new methods for selecting the number of hidden-layer neurons in the E-PQNN. The weights are optimized using a modified perceptron error criterion and a conjugate gradient optimizer. We present results obtained for a synthetic problem.

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