Boron-rich, cytocompatible block copolymer nanoparticles by polymerization-induced self-assembly

Core-shell nanoparticles (NPs) with a boron-rich core were synthesized by RAFT-mediated polymerization-induced self-assembly using a new methacrylic boronate ester monomer. Under specific conditions, sub-100 nm spherical NPs could be obtained at high conversions by either emulsion or dispersion RAFT polymerization using poly(oligo(ethylene glycol) methacrylate) (POEGMA) dithiobenozate-based chain transfer agents. Phenylboronic acid surface-functionalized NPs were obtained using a telechelic POEGMA. Primary data on biocompatibility is provided and suggests suitability as boron delivery agent for boron neutron capture therapy

All grown up? The fate after 15 years of a quarter of a million UK firms born in 1998

The theory of firm growth is in a rather unsatisfactory state. However, the analysis of large firm-level datasets which have become available in recent years allows us to begin building an evidence base which can, in turn, be used to underpin the development of more satisfactory theory. Here we study the 239 thousand UK private sector firms born in 1998 over their first 15 years of life. A first, and quite striking, finding is the extraordinary force of mortality. By age 15, 90% of the UK firms born in 1998 are dead, and, for those surviving to age 15, the hazard of death is still about 10% a year. The chance of death is related to the size and growth of firms in an interesting way. Whilst the hazard rate after 15 years is largely independent of size at birth, it is strongly affected by the current (age 14) size. In particular, firms with more than five employees are half as likely to die in the next year as firms with less than five employees. A second important finding is that most firms, even those which survive to age 15, do not grow very much. By age 15 more than half the 26,000 survivors still have less than five jobs. In other words, the growth paths – what we call the ‘growth trajectories’ – of most of the 26,000 survivors are pretty flat. However, of the firms that do grow, firms born smaller grow faster than those born larger. Another striking finding is that growth is heavily concentrated in the first five years. Whilst growth does continue, even up to age 15, each year after age five it involves only a relatively small proportion of firms. Finally, there are two groups of survivors which contribute importantly to job creation. Some are those born relatively large (with more than 20 jobs) although their growth rate is quite modest. More striking though, is a very small group of firms born very small with less than five jobs (about 5% of all survivors) which contribute a substantial proportion (more than one third) of the jobs added to the cohort total by age 15

The Physics of the B Factories

This work is on the Physics of the B Factories. Part A of this book contains a brief description of the SLAC and KEK B Factories as well as their detectors, BaBar and Belle, and data taking related issues. Part B discusses tools and methods used by the experiments in order to obtain results. The results themselves can be found in Part C

Measurement of the e^(+)e^(-)→ bb(macron) cross section between √s = 10.54 and 11.20 GeV

We report e^(+)e^(-)→ bb(macron) cross section measurements by the BABAR experiment performed during an energy scan in the range of 10.54 to 11.20 GeV at the SLAC PEP-II e^(+)e^(-) collider. A total relative error of about 5% is reached in more than 300 center-of-mass energy steps, separated by about 5 MeV. These measurements can be used to derive precise information on the parameters of the Y (10860) and Y (11020) resonances. In particular we show that their widths may be smaller than previously measured

Revisiting the stress paradigm for silica nanoparticles: Decoupling of the anti-oxidative defense, pro-inflammatory response and cytotoxicity.

Engineered amorphous silica nanoparticles (nanosilica) are widely used in industry yet can induce adverse effects, which might be classified according to the oxidative stress model. However, the underlying mechanisms as well as the potential interactions of the three postulated different tiers of toxicity—i.e. oxidative-, pro-inflammatory- and cytotoxic-stress response—are poorly understood. As macrophages are primary targets of nanoparticles, we used several macrophage models, primarily murine RAW264.7 macrophages, and monitored pro-inflammatory and anti-oxidative reactions as well as cytotoxicity in response to nanosilica at max. 50 µg/mL. Special attention was given to the activation of mitogen-activated protein kinases (MAPKs) as potential regulators of the cellular stress response. Indeed, according to the oxidative stress model, also nanosilica elicits an, albeit modest, anti-oxidative response as well as pronounced pro-inflammatory reactions and cytotoxicity in macrophages. Interestingly however, these three tiers of toxicity seem to operate separately of each other for nanosilica. Specifically, impeding the anti-oxidative response by scavenging of reactive oxygen species does not prevent the pro-inflammatory and cytotoxic response. Furthermore, blocking the pro-inflammatory response by inhibition of MAPKs does not impair cell death. As hazard assessment has been guided by the prevailing assumption of a dose-dependent coupling of sequential tiers of toxicity, identification of critical physico-chemical parameters to assist the safe-by-design concept should be enabled by simply monitoring one of the toxicity read-outs. Our results indicate a more complex scenario in the case of nanosilica, which triggers independent pleiotropic effects possibly also related to different material properties and primary cellular targets

Biocompatibility of amine-functionalized silica nanoparticles: The role of surface coverage.

Here, amorphous silica nanoparticles (NPs), one of the most abundant nanomaterials, are used as an example to illustrate the utmost importance of surface coverage by functional groups which critically determines biocompatibility. Silica NPs are functionalized with increasing amounts of amino groups, and the number of surface exposed groups is quantified and characterized by detailed NMR and fluorescamine binding studies. Subsequent biocompatibility studies in the absence of serum demonstrate that, irrespective of surface modification, both plain and amine-modified silica NPs trigger cell death in RAW 264.7 macrophages. The in vitro results can be confirmed in vivo and are predictive for the inflammatory potential in murine lungs. In the presence of serum proteins, on the other hand, a replacement of only 10% of surface-active silanol groups by amines is sufficient to suppress cytotoxicity, emphasizing the relevance of exposure conditions. Mechanistic investigations identify a key role of lysosomal injury for cytotoxicity only in the presence, but not in the absence, of serum proteins. In conclusion, this work shows the critical need to rigorously characterize the surface coverage of NPs by their constituent functional groups, as well as the impact of serum, to reliably establish quantitative nanostructure activity relationships and develop safe nanomaterials

Photon Beamlines and Diagnostics at LCLS

The Linac Coherent Light Source (LCLS) is the first hard-x-ray free electron laser in operation. The turn-on of LCLS was rapid and operation has been reliable. Performance has exceeded the design parameters in several areas. The photon energy output covers a range from 480 eV to over 9 keV; the pulse energy is typically 2-3 mJ, with a maximum of 4 mJ at 2 keV. Electron pulse lengths can be varied from 500 fs to shorter than 10 fs. A low-charge option at 20 pC is being explored, which delivers pulses shorter than 10 fs with a reduced pulse energy, typically around 0.2 mJ. On-demand, single-shot and multi-shot modes up to 60 Hz (planned is 120 Hz) can be made available. The photon diagnostics built for LCLS have been commissioned and provide measurements of various properties of the FEL beam, such as pulse energy, beam size and position, wavelength, and allows for intensity attenuation over the entire wavelength range. The two soft x-ray instruments, the Atomic Molecular and Optics (AMO) and Soft X-ray Material Science (SXR) stations, are fully operational and completed their second user run in mid September 2010. The third user run is scheduled from October to December 2010, and will include the first hard x-ray instrument X-ray Pump-and-Probe (XPP). Three additional hard x-ray stations will follow: CXI (Coherent X-ray Imaging) is planned to start commissioning in December 2010, the XCS (X-ray correlation spectroscopy) instrument will start in June 2011, and the station for Matter in Extreme Conditions (MEC) in 2012. A list of past and future milestones for LCLS commission and operations is shown in table 1. The LCLS hard x-ray Free Electron Laser at SLAC reported first lasing in April of 2009. Since then two successful user runs have been completed at the two soft x-ray stations. The first hard x-ray station has started commissioning in July of 2010. Beam diagnostics play an essential role for tuning the machine and delivering the requested beam properties to the users. An overview of the LCLS photon diagnostics will be presented including some selected commissioning results. Plans for future improvements and upgrades will be briefly discussed