Guidelines for the use of cell lines in biomedical research

Cell-line misidentification and contamination with microorganisms, such as mycoplasma, together with instability, both genetic and phenotypic, are among the problems that continue to affect cell culture. Many of these problems are avoidable with the necessary foresight, and these Guidelines have been prepared to provide those new to the field and others engaged in teaching and instruction with the information necessary to increase their awareness of the problems and to enable them to deal with them effectively. The Guidelines cover areas such as development, acquisition, authentication, cryopreservation, transfer of cell lines between laboratories, microbial contamination, characterisation, instability and misidentification. Advice is also given on complying with current legal and ethical requirements when deriving cell lines from human and animal tissues, the selection and maintenance of equipment and how to deal with problems that may arise

The Microarcsecond Sky and Cosmic Turbulence

Radio waves are imprinted with propagation effects from ionized media through which they pass. Owing to electron density fluctuations, compact sources (pulsars, masers, and compact extragalactic sources) can display a wide variety of scattering effects. These scattering effects, particularly interstellar scintillation, can be exploited to provide *superresolution*, with achievable angular resolutions (<~ 1 microarcsecond) far in excess of what can be obtained by very long baseline interferometry on terrestrial baselines. Scattering effects also provide a powerful sub-AU probe of the microphysics of the interstellar medium, potentially to spatial scales smaller than 100 km, as well as a tracer of the Galactic distribution of energy input into the interstellar medium through a variety of integrated measures. Coupled with future gamma-ray observations, SKA observations also may provide a means of detecting fainter compact gamma-ray sources. Though it is not yet clear that propagation effects due to the intergalactic medium are significant, the SKA will either detect or place stringent constraints on intergalactic scattering.Comment: 20 pages, 8 figures in 8 PostScript files, to appear in "Science with the Square Kilometer Array," eds. C. Carilli and S. Rawlings, New Astronomy Reviews (Elsevier: Amsterdam

Gravitational Lensing at Millimeter Wavelengths

With today's millimeter and submillimeter instruments observers use gravitational lensing mostly as a tool to boost the sensitivity when observing distant objects. This is evident through the dominance of gravitationally lensed objects among those detected in CO rotational lines at z>1. It is also evident in the use of lensing magnification by galaxy clusters in order to reach faint submm/mm continuum sources. There are, however, a few cases where millimeter lines have been directly involved in understanding lensing configurations. Future mm/submm instruments, such as the ALMA interferometer, will have both the sensitivity and the angular resolution to allow detailed observations of gravitational lenses. The almost constant sensitivity to dust emission over the redshift range z=1-10 means that the likelihood for strong lensing of dust continuum sources is much higher than for optically selected sources. A large number of new strong lenses are therefore likely to be discovered with ALMA, allowing a direct assessment of cosmological parameters through lens statistics. Combined with an angular resolution <0.1", ALMA will also be efficient for probing the gravitational potential of galaxy clusters, where we will be able to study both the sources and the lenses themselves, free of obscuration and extinction corrections, derive rotation curves for the lenses, their orientation and, thus, greatly constrain lens models.Comment: 69 pages, Review on quasar lensing. Part of a LNP Topical Volume on "Dark matter and gravitational lensing", eds. F. Courbin, D. Minniti. To be published by Springer-Verlag 2002. Paper with full resolution figures can be found at ftp://oden.oso.chalmers.se/pub/tommy/mmviews.ps.g

Signals for Lorentz Violation in Electrodynamics

An investigation is performed of the Lorentz-violating electrodynamics extracted from the renormalizable sector of the general Lorentz- and CPT-violating standard-model extension. Among the unconventional properties of radiation arising from Lorentz violation is birefringence of the vacuum. Limits on the dispersion of light produced by galactic and extragalactic objects provide bounds of 3 x 10^{-16} on certain coefficients for Lorentz violation in the photon sector. The comparative spectral polarimetry of light from cosmologically distant sources yields stringent constraints of 2 x 10^{-32}. All remaining coefficients in the photon sector are measurable in high-sensitivity tests involving cavity-stabilized oscillators. Experimental configurations in Earth- and space-based laboratories are considered that involve optical or microwave cavities and that could be implemented using existing technology.Comment: 23 pages REVTe

Validating reduced models for detachment onset and reattachment times on MAST-U

Two reduced models for predicting detachment onset and divertor reattachment times are validated on MAST Upgrade (MAST-U). These models are essential for future tokamak reactor design, providing rapid calculations based primarily on engineering parameters. The first model predicts detachment onset using a qualifier developed on ASDEX Upgrade (AUG) and later tested on JET, while the second model provides an estimate for the time required for a given transient to burn through the neutral particles in the divertor. Experiments in H-mode plasma scenarios were conducted on MAST-U with double-null and single-null configurations, which involved D2 fuelling ramps and N2 seeding. The detachment onset was determined by monitoring divertor parameters, including the target heat flux profile, electron temperature, and electron density, with measurements showing consistency with AUG-derived predictions. Reattachment times were assessed during dynamic vertical shifts of the plasma centroid position, with observations indicating reattachment within milliseconds, consistent with model predictions. Overall, the results confirm the applicability of both reduced models to MAST-U, extending their validation beyond AUG and JET.</p

Potency enhancement of the κ-opioid receptor antagonist probe ML140 through sulfonamide constraint utilizing a tetrahydroisoquinoline motif

Optimization of the sulfonamide-based kappa opioid receptor (KOR) antagonist probe molecule ML140 through constraint of the sulfonamide nitrogen within a tetrahydroisoquinoline moiety afforded a marked increase in potency. This strategy, when combined with additional structure-activity relationship exploration, has led to a compound only six-fold less potent than norBNI, a widely utilized KOR antagonist tool compound, but significantly more synthetically accessible. The new optimized probe is suitably potent for use as an in vivo tool to investigate the therapeutic potential of KOR antagonists

Development of functionally selective, small molecule agonists at kappa opioid receptors

The kappa opioid receptor (KOR) is widely expressed in the CNS and can serve as a means to modulate pain perception, stress responses, and affective reward states. Therefore, the KOR has become a prominent drug discovery target toward treating pain, depression, and drug addiction. Agonists at KOR can promote G protein coupling and βarrestin2 recruitment as well as multiple downstream signaling pathways, including ERK1/2 MAPK activation. It has been suggested that the physiological effects ofKORactivation result from different signaling cascades, with analgesia being G protein-mediated and dysphoria being mediated through βarrestin2 recruitment. Dysphoria associated with KOR activation limits the therapeutic potential in the use of KOR agonists as analgesics; therefore, it may be beneficial to develop KOR agonists that are biased toward G protein coupling and away from βarrestin2 recruitment. Here, we describe two classes of biased KOR agonists that potently activateGprotein coupling but weakly recruitβarrestin2. These potent and functionally selective small molecule compounds may prove to be useful tools for refining the therapeutic potential of KOR-directed signaling in vivo

Acceleration of Relativistic Protons during the 20 January 2005 Flare and CME

The origin of relativistic solar protons during large flare/CME events has not been uniquely identified so far.We perform a detailed comparative analysis of the time profiles of relativistic protons detected by the worldwide network of neutron monitors at Earth with electromagnetic signatures of particle acceleration in the solar corona during the large particle event of 20 January 2005. The intensity-time profile of the relativistic protons derived from the neutron monitor data indicates two successive peaks. We show that microwave, hard X-ray and gamma-ray emissions display several episodes of particle acceleration within the impulsive flare phase. The first relativistic protons detected at Earth are accelerated together with relativistic electrons and with protons that produce pion decay gamma-rays during the second episode. The second peak in the relativistic proton profile at Earth is accompanied by new signatures of particle acceleration in the corona within approximatively 1 solar radius above the photosphere, revealed by hard X-ray and microwave emissions of low intensity, and by the renewed radio emission of electron beams and of a coronal shock wave. We discuss the observations in terms of different scenarios of particle acceleration in the corona.Comment: 22 pages, 5 figure