The studies concerning clinical implications of TET2 mutation in patients with primary acute myeloid leukemia (AML) are scarce. We analyzed TET2 mutation in 486 adult patients with primary AML. TET2 mutation occurred in 13.2% of our patients and was closely associated with older age, higher white blood cell and blast counts, lower platelet numbers, normal karyotype, intermediate-risk cytogenetics, isolated trisomy 8, NPM1 mutation, and ASXL1 mutation but mutually exclusive with IDH mutation. TET2 mutation is an unfavorable prognostic factor in patients with intermediate-risk cytogenetics, and its negative impact was further enhanced when the mutation was combined with FLT3-ITD, NPM1-wild, or unfavorable genotypes (other than NPM1 ؉ /FLT3-ITD ؊ or CEBPA ؉ ). A scoring system integrating TET2 mutation with FLT3-ITD, NPM1, and CEBPA mutations could well separate AML patients with intermediate-risk cytogenetics into 4 groups with different prognoses (P < .0001). Sequential analysis revealed that TET2 mutation detected at diagnosis was frequently lost at relapse; rarely, the mutation was acquired at relapse in those without TET2 mutation at diagnosis. In conclusion, TET2 mutation is associated with poor prognosis in AML patients with intermediate-risk cytogenetics, especially when it is combined with other adverse molecular markers. TET2 mutation appeared to be unstable during disease evolution. (Blood. 2011;118(14): 3803-3810)

Lung stem/progenitor cells are potentially useful for regenerative therapy, for example in repairing damaged or lost lung tissue in patients. Several optical imaging methods and probes have been used to track how stem cells incorporate and regenerate themselves in vivo over time. However, these approaches are limited by photobleaching, toxicity and interference from background tissue autofluorescence. Here we show that fluorescent nanodiamonds, in combination with fluorescence-activated cell sorting, fluorescence lifetime imaging microscopy and immunostaining, can identify transplanted CD45(-)CD54(+)CD157(+) lung stem/progenitor cells in vivo, and track their engraftment and regenerative capabilities with single-cell resolution. Fluorescent nanodiamond labelling did not eliminate the cells' properties of self-renewal and differentiation into type I and type II pneumocytes. Time-gated fluorescence imaging of tissue sections of naphthalene-injured mice indicates that the fluorescent nanodiamond-labelled lung stem/progenitor cells preferentially reside at terminal bronchioles of the lungs for 7 days after intravenous transplantation.

A bunch of loners: Fluorescent nanodiamonds (FNDs) noncovalently conjugated with bovine serum albumin (BSA) or α‐lactalbumin exhibited good dispersibility in a buffer with only minor or no agglomeration. They are useful as photostable fluorescent markers in cells for superresolution imaging by STED (see confocal fluorescence image of an FND‐labeled cell (left) and STED image of single BSA‐conjugated FNDs (right)).

We report on SwissSPAD2, an image sensor with 512×512 photon-counting pixels, each comprising a single-photon avalanche diode (SPAD), a 1-bit memory, and a gating mechanism capable of turning the SPAD on and off, with a skew of 250ps and 344ps, respectively, for a minimum duration of 5.75ns. The sensor is designed to achieve a frame rate of up to 97,700 binary frames per second and sub-40ps gate shifts. By synchronizing it with a pulsed laser and using multiple successive overlapping gates, one can reconstruct a molecule’s fluorescent response with picosecond temporal resolution. Thanks to the sensor’s number of pixels (the largest to date) and the fully integrated gated operation, SwissSPAD2 enables widefield FLIM with an all-solid-state solution and at relatively high frame rates. This was demonstrated with preliminary results on organic dyes and semiconductor quantum dots using both decay fitting and phasor analysis. Furthermore, pixels with an exceptionally low dark count rate and high photon detection probability enable uniform and high quality imaging of biologically relevant fluorescent samples stained with multiple dyes. While future versions will feature the addition of microlenses and optimize firmware speed, our results open the way to low-cost alternatives to commercially available scientific time-resolved imagers.

Solutions of two biodegradable polymers, that is, poly(dl-lactic acid) (PDLLA) and poly(3-hydroxy butyrate) (PHB), were individually delivered to the inner and outer channel of a coaxial-tube spinneret for electrospinning to prepare core−shell fibers used for drug release applications. By interchanging the inner- and outer-channel solutions, either PDLLA/PHB or PHB/PDLLA core−shell fibers could be conveniently obtained. Their fiber diameters were readily controlled by the flow rate of the core fluid (Q c). The effects of Q c on the morphologies of the Taylor cone, the whipping jet, and the electrospun fibers were investigated. Several scaling laws describing the Q c dependence of the outer fiber diameter (D f) and the inner fiber diameter (d f) were derived, that is, D f ∼ Q c 0.02 and d f ∼ Q c 0.18 for the PDLLA/PHB fluids and D f ∼ Q c 0.30 and d f ∼ Q c 0.59 for the PHB/PDLLA fluids. These scaling laws provided the processing guidelines for the manipulation of the final diameters of the core−shell fibers for a given pair of electrospinning solutions. The microstructure revealed by differential scanning calorimetry, Fourier transform infrared spectroscopy, and wide-angle X-ray diffraction showed that the PDLLA component was in the amorphous state. In addition, the crystallizability of the PHB component remained relatively unchanged despite the reduction of its measured melting enthalpy when the PDLLA content was increased through an increase in its flow rate. By controlling Q c, PDLLA/PHB fibers with a PHB shell of a similar crystallinity but with different thicknesses were readily obtained and used for the sustained release of dimethyloxalylglycine (DMOG) drug, which is a proangiogenic compound acting via the hypoxia-inducible factor system. In contrast with the single-component PDLLA and PHB fibers, which exhibited a burst release behavior, two-stage release kinetics was observed for the present PDLLA/PHB fibers when DMOG was embedded in the core section: an initial fast release before the inflections followed by a constant release. For the first stage, the amount released was ∼25% within 60 h, irrespective of the PHB thickness. After the burst release, DMOG was linearly released up to an amount of 70%, and the release rate was feasibly controlled by the thickness of the PHB shell.

In the present study, a theoretical model was used to examine factors affecting the filtration characteristics of filters used for respiratory protection. This work was designed to support the particulate filter test requirements established in 1996. The major operating parameters examined in this work include face velocity, fiber diameter, packing density, filter thickness, and fiber charge density. Characteristics of the most penetrating particle size were also modeled with the same operating parameters.The results showed that aerosol penetration through electret filter media increases with increasing face velocity and increasing fiber diameter, and decreases as packing density, filter thickness or fiber charge density increase. Face velocity and fiber charge density have more significant effects on filter quality than the other factors. Filter quality increases with decreasing face velocity or increasing fiber charge density. For electret filters, (1) the most penetrating particle size increases with increasing fiber diameter; (2) an increase in packing density, thickness, or fiber charge density would cause the most penetrating particle size to decrease, and (3) the most penetrating particle size through electret filters increases with increasing face velocity and decreasing filter thickness. On the other hand, for non-electret filter media, the most penetrating particle size increases with decreasing face velocity, and the filter quality factor is not affected by filter thickness.

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