Targeting O 6-methylguanine-DNA methyltransferase with specific inhibitors as a strategy in cancer therapy

O ⁶-methylguanine-DNA methyltransferase (MGMT) repairs the cancer chemotherapy-relevant DNA adducts, O ⁶-methylguanine and O ⁶-chloroethylguanine, induced by methylating and chloroethylating anticancer drugs, respectively. These adducts are cytotoxic, and given the overwhelming evidence that MGMT is a key factor in resistance, strategies for inactivating MGMT have been pursued. A number of drugs have been shown to inactivate MGMT in cells, human tumour models and cancer patients, and O ⁶-benzylguanine and O ⁶-[4-bromothenyl]guanine have been used in clinical trials. While these agents show no side effects per se, they also inactivate MGMT in normal tissues and hence exacerbate the toxic side effects of the alkylating drugs, requiring dose reduction. This might explain why, in any of the reported trials, the outcome has not been improved by their inclusion. It is, however, anticipated that, with the availability of tumour targeting strategies and hematopoetic stem cell protection, MGMT inactivators hold promise for enhancing the effectiveness of alkylating agent chemotherapy.     

Liquid marbles.

The transport of a small amount of liquid on a solid is not a simple process, owing to the nature of the contact between the two phases. Setting a liquid droplet in motion requires non-negligible forces (because the contact-angle hysteresis generates a force opposing the motion), and often results in the deposition of liquid behind the drop. Different methods of levitation-electrostatic, electromagnetic, acoustic, or even simpler aerodynamic techniques-have been proposed to avoid this wetting problem, but all have proved to be rather cumbersome. Here we propose a simple alternative, which consists of encapsulating an aqueous liquid droplet with a hydrophobic powder. The resulting 'liquid marbles' are found to behave like a soft solid, and show dramatically reduced adhesion to a solid surface. As a result, motion can be generated using gravitational, electrical and magnetic fields. Moreover, because the viscous friction associated with motion is very small, we can achieve quick displacements of the droplets without any leaks. All of these features are of potential benefit in microfluidic applications, and also permit the study of a drop in a non-wetting situation-an issue of renewed interest following the recent achievement of super-hydrophobic substrates.     

On-chip natural assembly of silicon photonic bandgap crystals.

Photonic bandgap crystals can reflect light for any direction of propagation in specific wavelength ranges. This property, which can be used to confine, manipulate and guide photons, should allow the creation of all-optical integrated circuits. To achieve this goal, conventional semiconductor nanofabrication techniques have been adapted to make photonic crystals. A potentially simpler and cheaper approach for creating three-dimensional periodic structures is the natural assembly of colloidal microspheres. However, this approach yields irregular, polycrystalline photonic crystals that are difficult to incorporate into a device. More importantly, it leads to many structural defects that can destroy the photonic bandgap. Here we show that by assembling a thin layer of colloidal spheres on a silicon substrate, we can obtain planar, single-crystalline silicon photonic crystals that have defect densities sufficiently low that the bandgap survives. As expected from theory, we observe unity reflectance in two crystalline directions of our photonic crystals around a wavelength of 1.3 micrometres. We also show that additional fabrication steps, intentional doping and patterning, can be performed, so demonstrating the potential for specific device applications.     

How 'spin ice' freezes.

The large degeneracy of states resulting from the geometrical frustration of competing interactions is an essential ingredient of important problems in fields as diverse as magnetism, protein folding and neural networks. As first explained by Pauling, geometrical frustration of proton positions is also responsible for the unusual low-temperature thermodynamics of ice and its measured 'ground state' entropy. Recent work has shown that the geometrical frustration of ice is mimicked by Dy2Ti2O7, a site-ordered magnetic material in which the spins reside on a lattice of corner-sharing tetrahedra where they form an unusual magnetic ground state known as 'spin ice'. Here we identify a cooperative spin-freezing transition leading to the spin-ice ground state in Dy2Ti2O7. This transition is associated with a very narrow range of relaxation times, and represents a new form of spin-freezing. The dynamics are analogous to those associated with the freezing of protons in ice, and they provide a means through which to study glass-like behaviour and the consequences of frustration in the limit of low disorder.     

Superconductivity in CaCuO2 as a result of field-effect doping.

Understanding the doping mechanisms in the simplest superconducting copper oxide-the infinite-layer compound ACuO2 (where A is an alkaline earth metal)-is an excellent way of investigating the pairing mechanism in high-transition-temperature (high-Tc) superconductors more generally. Gate-induced modulation of the carrier concentration to obtain superconductivity is a powerful means of achieving such understanding: it minimizes the effects of potential scattering by impurities, and of structural modifications arising from chemical dopants. Here we report the transport properties of thin films of the infinite-layer compound CaCuO2 using field-effect doping. At high hole- and electron-doping levels, superconductivity is induced in the nominally insulating material. Maximum values of Tc of 89 K and 34 K are observed respectively for hole- and electron-type doping of around 0.15 charge carriers per CuO2. We can explore the whole doping diagram of the CuO2 plane while changing only a single electric parameter, the gate voltage.     

New cooperative frequency domain differential modulation and demodulation

An innovative method of cooperative frequency domain differential modulation and demodulation is presented.This method applies the prior knowledge of channel propagation to selecting the variable differential length and carrying out frequency domain modulation.This strategy optimizes the design of system parameters to effectively improve the anti-interference ability of the differential system in time-varied multipath channel circumstance without making the execution more complicating.The simulations and comparisons demonstrate the proposed method is effective,and the results show that it is especially suitable for the fading channel with strong propagation and fast time-variation.     

Community Development and Renaissance Social Humanism: Some Lessons for Systems Science

Starting from the crisis in our communities—research has indicated it to be widely spread—the author explores the scientific tradition preceding the rise of modernism in order to draw out a more humane way of thinking that may help our contemporary societies. He discerns between two types of Renaissance humanism, one characterised by its cleverness, the other by its compassion and desire to restore dignity to the lives of people struggling to escape the clutches of medievalism. The father of the latter is Erasmus of Rotterdam and we follow the development of his conception of a social humanism as it branches out, through the work of his successors, into every scientific discipline, both natural and human. These disciplines are united by an embracing systemic idea of philosophy that unites the mind with the heart and which Erasmus called “Philosophia Christi”. We examine the two main pillars upon which this philosophy is built, love for our neighbour and education as the only legitimate instrument to change society, and the extraordinary impact it had on science and on communities living in the seventeenth century. We contrast this with the idea of power, the chosen instrument of modernity to transform society, and trace some of its tragic outcomes. We conclude by discussing the incorporation of an Erasmian type of social humanism into systems education and the future development of such programmes.     

A very faint core-collapse supernova in M85

An anomalous transient in the early Hubble-type (S0) galaxy Messier 85 (M85) in the Virgo cluster was discovered by Kulkarni et al. on 7 January 2006 that had very low luminosity (peak absolute R-band magnitude M(R) of about -12) that was constant over more than 80 days, red colour and narrow spectral lines, which seem inconsistent with those observed in any known class of transient events. Kulkarni et al. suggest an exotic stellar merger as the possible origin. An alternative explanation is that the transient in M85 was a type II-plateau supernova of extremely low luminosity, exploding in a lenticular galaxy with residual star-forming activity. This intriguing transient might be the faintest supernova that has ever been discovered.     

Novel neurotrophic factor CDNF protects and rescues midbrain dopamine neurons in vivo

In Parkinson's disease, brain dopamine neurons degenerate most prominently in the substantia nigra. Neurotrophic factors promote survival, differentiation and maintenance of neurons in developing and adult vertebrate nervous system. The most potent neurotrophic factor for dopamine neurons described so far is the glial-cell-line-derived neurotrophic factor (GDNF). Here we have identified a conserved dopamine neurotrophic factor (CDNF) as a trophic factor for dopamine neurons. CDNF, together with its previously described vertebrate and invertebrate homologue the mesencephalic-astrocyte-derived neurotrophic factor, is a secreted protein with eight conserved cysteine residues, predicting a unique protein fold and defining a new, evolutionarily conserved protein family. CDNF (Armetl1) is expressed in several tissues of mouse and human, including the mouse embryonic and postnatal brain. In vivo, CDNF prevented the 6-hydroxydopamine (6-OHDA)-induced degeneration of dopaminergic neurons in a rat experimental model of Parkinson's disease. A single injection of CDNF before 6-OHDA delivery into the striatum significantly reduced amphetamine-induced ipsilateral turning behaviour and almost completely rescued dopaminergic tyrosine-hydroxylase-positive cells in the substantia nigra. When administered four weeks after 6-OHDA, intrastriatal injection of CDNF was able to restore the dopaminergic function and prevent the degeneration of dopaminergic neurons in substantia nigra. Thus, CDNF was at least as efficient as GDNF in both experimental settings. Our results suggest that CDNF might be beneficial for the treatment of Parkinson's disease.