Identification of a nonsense mutation in the granulocyte-colony-stimulating factor receptor in severe congenital neutropenia

Severe congenital neutropenia (Kostmann syndrome) is characterized by profound absolute neutropenia and a maturation arrest of marrow progenitor cells at the promyelocyte-myelocyte stage. Marrow cells from such patients frequently display a reduced responsiveness to granulocyte-colony-stimulating factor (G-CSF). G-CSF binds to and activates a specific receptor which transduces signals critical for the proliferation and maturation of granulocytic progenitor cells. Here we report the identification of a somatic point mutation in one allele of the G-CSF receptor gene in a patient with severe congenital neutropenia. The mutation results in a cytoplasmic truncation of the receptor. When expressed in murine myeloid cells, the mutant receptor transduced a strong growth signal but, in contrast to the wild-type G-CSF receptor, was defective in maturation induction. The mutant receptor chain may act in a dominant negative manner to block granulocytic maturation

Analysis and experimental validation of the figure of merit for piezoelectric energy harvesters

Piezoelectric energy harvesters are at the front of scientific research as enablers of renewable, sustainable energy for autonomous wireless sensor networks. Crucial for this disruptive technology is the achievable output power. Here we show, analytically, that the maximum output energy per unit volume, under a single sinusoidal excitation, is equal to 1/(4 − 2k2) × 1/2dgX2, where k2 is the electromechanical coupling coefficient, d and g are the piezoelectric charge and voltage coefficient, respectively, and X is the applied stress. The expression derived is validated by the experimentally measured output energy for a variety of piezoelectric materials over an unprecedented range of more than five orders of magnitude. As the prefactor 1/(4 − 2k2) varies only between 1/2 and 1/4 the figure of merit for piezoelectric materials for energy harvesters is not k2, as commonly accepted for vibrational harvesters, but dg. The figure of merit does not depend on the compliance, or Young's modulus. Hence we argue that commonly used brittle inorganic piezoelectric ceramics can be replaced by soft, mechanically flexible polymers and composite films, comprising inorganic piezoelectric materials embedded in a polymer matrix

Large area and flexible micro-porous piezoelectric materials for soft robotic skin

The need for flexible, highly sensitive tactile sensors that can fit onto curved surfaces is driving the conformable sensor materials research in the field of human–machine interactions. Here we report a new type of compliant piezoelectric active composite, a micro-porous polyurethane-PZT material, capable of generating a voltage output upon touch. The composites are synthesized with the aim of maximizing the piezoelectric sensitivity of particulate composite sensor materials. The goal is to reduce the dielectric constant of the polymer matrix and improve flexibility of conventional bulk piezo-composites, consisting of ceramic particles in a dense polymeric matrix, by adding a third (gaseous) phase to the system in the form of uniformly sized pores. The presence of the gaseous component in the polymer matrix in the form of well-distributed spherical inclusions effectively decreases the polymer dielectric permittivity, which increases the piezoelectric voltage sensitivity (g33) of the composite sensors significantly. The unique combination of dielectrophoretic structuring of PZT particles and the addition of a gaseous phase to the polymer resin results in the highest performance of the particulate composite sensors reported in the literature so far. The newly developed micro-porous composites show g33 value of 165 mV m/N that is twice that of the structured PZT-bulk PU composites (80 mV m/N) and more than five times the g33 value of bulk PZT ceramics (24–28 mV m/N). The capability of the flexible freestanding sensors for application in touch sensing devices for soft robotics is demonstrated

Large area and flexible micro-porous piezoelectric materials for soft robotic skin

The need for flexible, highly sensitive tactile sensors that can fit onto curved surfaces is driving the conformable sensor materials research in the field of human–machine interactions. Here we report a new type of compliant piezoelectric active composite, a micro-porous polyurethane-PZT material, capable of generating a voltage output upon touch. The composites are synthesized with the aim of maximizing the piezoelectric sensitivity of particulate composite sensor materials. The goal is to reduce the dielectric constant of the polymer matrix and improve flexibility of conventional bulk piezo-composites, consisting of ceramic particles in a dense polymeric matrix, by adding a third (gaseous) phase to the system in the form of uniformly sized pores. The presence of the gaseous component in the polymer matrix in the form of well-distributed spherical inclusions effectively decreases the polymer dielectric permittivity, which increases the piezoelectric voltage sensitivity (g33) of the composite sensors significantly. The unique combination of dielectrophoretic structuring of PZT particles and the addition of a gaseous phase to the polymer resin results in the highest performance of the particulate composite sensors reported in the literature so far. The newly developed micro-porous composites show g33 value of 165 mV m/N that is twice that of the structured PZT-bulk PU composites (80 mV m/N) and more than five times the g33 value of bulk PZT ceramics (24–28 mV m/N). The capability of the flexible freestanding sensors for application in touch sensing devices for soft robotics is demonstrated

Human primary T lymphocytes have a low capacity to amplify MLV-based amphotropic RCR and the virions produced are largely noninfectious

The presence of replication-competent retrovirus (RCR) in retroviral-based gene therapy products poses a potential safety risk for patients. Therefore, RCR testing of clinical gene therapy products and monitoring of patients enrolled in gene therapy trials is required to assure viral safety. The requirement to test ex vivo-transduced cells originates from the presumed amplification of adventitious RCR during the transduction procedure. However, data on the capacity of different cell types to do so are lacking. In this study, we sought to analyze the amplification potential of primary human T lymphocytes after infection with amphotropic MLV-based RCR. The total number of viral particles produced after 1 or 2 weeks was measured by a quantitative 4070A env-specific RT-PCR assay. The fraction of infectious replication-competent viral particles was analyzed in the PG-4 S+L- assay. From this study, we conclude that the total number of viral particles RCR produced by T lymphocytes is 2-4 logs lower than the number produced by NIH-3T3 cells. Surprisingly, less than 1% of the viral particles produced by primary T lymphocytes appeared to be infectious, while nearly all virions produced by NIH-3T3 were. We conclude that primary human T lymphocytes are low producers of MLV-based amphotropic RC