Measurements of the XUV mass absorption coefficient of an overdense liquid metal

The increase in the XUV mass absorption coefficient of liquid aluminium, produced by high-power-laser shock-compression, is measured using XUV laser radiography. At a photon energy of 63 eV a change in the mass absorption coefficient by up to a factor of similar to2.2 is determined at densities close to twice that of solid and electron temperatures of the order of 1 eV. Comparison with hydrodynamic simulations indicate that the absorption coefficient scales with density as rho (1.3 +/-0.2).

SiO in G34.26: Outflows and shocks in a high mass star forming region

We have looked for SiO emission as evidence of shocks in the high mass star formation region G34.26+0.15. JCMT, VLA and FCRAO observations show that SiO emission is widespread across the region. The SiO emission highlights a massive, collimated out ow and other regions where stellar winds are interacting with molecular clumps. As in other star forming regions, there is also SiO at ambient velocities which is related to the out ow activity. No strong SiO abundance enhancement was measured in either the out ow or the low velocity gas, though abundances up to 10(-8) are possible if the SiO is locally enhanced in clumps and optically thick. SiO emission is not detected from the hot core itself, indicating either that SiO is not strongly enhanced in the hot core or that column densities in the region where grain mantle evaporation has taken place are low. In line of sight spiral arm clouds, we measure a SiO abundance of 0.4-2 x 10(-10), consistent with previous estimates for quiescent clouds.

Molecular abundances in the magellanic clouds .1. A multiline study of five cloud cores

Nine H II regions of the LMC were mapped in (CO)-C-13(1-0) and three in (CO)-C-12(1-0) to study the physical properties of the interstellar medium in the Magellanic Clouds. For N113 the molecular core is found to have a peak position which differs from that of the associated H II region by 20 ''. Toward this molecular core the (CO)-C-12 and (CO)-C-13 peak T-MB line temperatures of 7.3 K and 1.2 K are the highest so far found in the Magellanic Clouds. The molecular concentrations associated with N113, N44BC, N159HW, and N214DE in the LMC and LIRS 36 in the SMC were investigated in a variety of molecular species to study the chemical properties of the interstellar medium. I(HCO+)/I(HCN) and I(HCN)/I(HNC) intensity ratios as well as lower limits to the I((CO)-C-13)/I((CO)-O-18) ratio were derived for the rotational 1-0 transitions. Generally, HCO+ is stronger than HCN, and HCN is stronger than HNC. The high relative HCO+ intensities are consistent with a high ionization flux from supernovae remnants and young stars, possibly coupled with a large extent of the HCO+ emission region. The bulk of the HCN arises from relatively compact dense cloud cores. Warm or shocked gas enhances HCN relative to HNC. From chemical model calculations it is predicted that I(HCN)/I(HNC) close to one should be obtained with higher angular resolution (less than or similar to 30 '') toward the cloud cores. Comparing virial masses with those obtained from the integrated CO intensity provides an H-2 mass-to-CO luminosity conversion factor of 1.8 x 10(20) mol cm(-2) (K km s(-1))(-1) for N113 and 2.4 x 10(20) mol cm(-2) (K km s(-1))(-1) for N44BC. This is consistent with values derived for the Galactic disk.

Molecular abundances in the Magellanic Clouds .2. Deuterated species in the LMC

The first definite discoveries of extragalactic deuterium are reported. DCO+ has been detected in three and DCN has been measured in one star-forming region of the Large Magellanic Cloud (LMC). While the HCO+/DCO+ abundance ratios are found to be 19 +/- 3, 24 +/- 4, and 67 +/- 18 for N113, N44BC and N159HW, respectively, a HCN/DCN abundance ratio of 23 +/- 5 is obtained for N113. These results are consistent with a gas temperature of about 20 K and a D/H ratio of about 1.5 x 10(-5), consistent with that observed in the Galaxy. If the cloud temperature is closer to 30 K, then a D/H ratio is required to be up to an order of magnitude larger. Because this ratio provides a lower limit to the primordial D/H ratio, it indicates that the baryon mass density alone is unable to close the universe.

Energy distributions of copper ions and atoms sputtered by atomic and molecular ions

Non-resonant multiphoton ionization combined with quadrupole and time-of-flight analysis has been used to study sputtering by both atomic and molecular ion beams. The mass spectra and energy distributions of both sputtered atoms and secondary ions produced by 3.6 keV Ar+, N+, N-2(+), CF2+ and CF3+ ion bombardment at 45 degrees to a polycrystalline copper target have been measured. The energy distributions of the copper ions and atoms are found to be different and quite complex. The ion distributions can generally be described by a linear collision cascade model, with possible evidence for a knock-on contribution. The sputtered atom distributions are partially described by a combination of linear collision cascade and dense cascade (thermal spike) models. This is interpreted as support for a time-evolving sputtering mechanism.

Changing climate, changing process: implications for salt transportation and weathering within building sandstones in the UK

Salt weathering is a crucial process that brings about a change in stone, from the scale of landscapes to stone outcrops and natural building stone facades. It is acknowledged that salt weathering is controlled by fluctuations in temperature and moisture, where repeated oscillations in these parameters can cause re-crystallisation, hydration/de-hydration of salts, bringing about stone surface loss in the form of, for example, granular disaggregation, scaling, and multiple flaking. However, this ‘traditional’ view of how salt weathering proceeds may need to be re-evaluated in the light of current and future climatic trends. Indeed, there is considerable scope for the investigation of consequences of climate change on geomorphological processes in general. Building on contemporary research on the ‘deep wetting’ of natural building stones, it is proposed that (as stone may be wetter for longer), ion diffusion may become a more prominent mechanism for the mixing of molecular constituents, and a shift in focus from physical damage to chemical change is suggested. Data from ion diffusion cell experiments are presented for three different sandstone types, demonstrating that salts may diffuse through porous stone relatively rapidly (in comparison to, for example, dense concrete). Pore water from stones undergoing diffusion experiments was extracted and analysed. Factors controlling ion diffusion
relating to ‘time of wetness’ within stones are discussed, (continued saturation, connectivity of pores, mineralogy, behaviour of salts, sedimentary structure), and potential changes in system dynamics as a result of climate change are addressed. System inputs may change in terms of increased moisture input, translating into a greater depth of wetting front. Salts are likely to be ‘stored’ differently in stones, with salt being in solution for longer periods (during prolonged winter wetness). This has myriad implications in terms of the movement of ions by diffusion and the potential for chemical change in the stone (especially in more mobile constituents), leading to a weakening of the stone matrix/grain boundary cementing. The ‘output’ may be mobilisation and precipitation of elements leading to, for example, uneven cementing in the stone. This reduced strength of the stone, or compromised ability of the stone to absorb stress, is likely to make crystallisation a more efficacious mechanism of decay when it does occur. Thus, a delay in the onset of crystallisation while stonework is wet does not preclude exaggerated or accelerated material loss when it finally happens.

Molecular line emission from a protoplanetary disk irradiated externally by a nearby massive star

Star formation often occurs within or nearby stellar clusters. Irradiation by nearby massive stars can photoevaporate protoplanetary disks around young stars (so-called proplyds) which raises questions regarding the ability of planet formation to take place in these environments. We investigate the two-dimensional physical and chemical structure of a protoplanetary disk surrounding a low-mass (T Tauri) star which is irradiated by a nearby massive O-type star to determine the survivability and observability of molecules in proplyds. Compared with an isolated star-disk system, the gas temperature ranges from a factor of a few (in the disk midplane) to around two orders of magnitude (in the disk surface) higher in the irradiated disk. Although the UV flux in the outer disk, in particular, is several orders of magnitude higher, the surface density of the disk is sufficient for effective shielding of the disk midplane so that the disk remains predominantly molecular in nature. We also find that non-volatile molecules, such as HCN and H2O, are able to freeze out onto dust grains in the disk midplane so that the formation of icy planetesimals, e.g., comets, may also be possible in proplyds. We have calculated the molecular line emission from the disk assuming LTE and determined that multiple transitions of atomic carbon, CO (and isotopologues, 13CO and C18O), HCO+, CN, and HCN may be observable with ALMA, allowing characterization of the gas column density, temperature, and optical depth in proplyds at the distance of Orion (˜400 pc).

Self-assembly of hybrid organic–inorganic polyoxovanadates: functionalised mixed-valent clusters and molecular cages’

Herein we report the intra- and inter-molecular assembly of a {V5O9} subunit. This mixed-valent structural motif can be stabilised as [V5O9(L1–3)4]5−/9− (1–3) by a range of organoarsonate ligands (L1–L3) whose secondary functionalities influence its packing arrangement within the crystal structures. Variation of the reaction conditions results in the dodecanuclear cage structure [V12O14(OH)4(L1)10]4− (4) where two modified convex building units are linked via two dimeric {O4VIV(OH)2VIVO4} moieties. Bi-functional phosphonate ligands, L4–L6 allow the intramolecular connectivity of the {V5O9} subunit to give hybrid capsules [V10O18(L4–6)4]10− (5–7). The dimensions of the electrophilic cavities of the capsular entities are determined by the incorporated ligand type. Mass spectrometry experiments confirm the stability of the complexes in solution. We investigate and model the temperature-dependent magnetic properties of representative complexes 1, 4, 6 and 7 and provide preliminary cell-viability studies of three different cancer cell lines with respect to Na8H2[6]·36H2O and Na8H2[7]·2DMF·29H2O.

Molecular Cloning of a Novel Tryptophyllin Peptide from the Skin of the Orange-Legged Monkey Frog, Phyllomedusa hypochondrialis

Tryptophyllins are a group of small (4–14 amino acids), heterogenous peptides, mostly from the skins of hylid frogs from the genera, Phyllomedusa and Litoria. To date, more than forty TPHs have been discovered in species from these two genera. Here, we describe the identification of a novel tryptophyllin type 3 peptide, PhT-3, from the extracts of skin of the orange-legged monkey frog, Phyllomedusa hypochondrialis, and molecular cloning of its precursor-encoding cDNA from a cDNA library constructed from the same skin sample. Full primary structural characterization was achieved using a combination of direct Edman degradation, mass spectrometry and deduction from cloned skin-derived cDNA. The open-reading frame of the precursor cDNA was found to consist of 63 amino acid residues. The mature peptide arising from this precursor contains a post-translationally modified N-terminal pyroglutamate (pGlu) residue, formed from acid-mediated cyclization of an N-terminal Gln (Q) residue, and with the structure: pGlu-Asp-Lys-Pro-Phe-Trp-Pro-Pro-Pro-Ile-Tyr-Pro-Met. Pharmacological assessment of a synthetic replicate of this peptide on phenylephrine preconstricted rat tail artery segments, revealed a reduction in relaxation induced by bradykinin. PhT-3 was also found to mediate antiproliferative effects on human prostate cancer cell lines.

Irradiation of oxygen and water ices at by 4 keV singly and doubly charged ions; sputtering and molecular synthesis

The icy surfaces of dust grains in the Interstellar Medium and those of comets, satellites and Kuiper Belt Objects are continuously exposed tophoton and charged particle irradiation. These energetic particles maysputter and induce chemical changes in the ices and the underlyingsurfaces.In the present work 258 nm thick O2 and H2O ices were deposited at 10 K with the thickness measured by a laser interferometer method. Asimple model fit to the reflected laser intensity as measured by aphotodiode detector enabled the refractive index of the ices to bedetermined. The ices were then irradiated with various singly and doublycharged ions such as He+, 13C+, N+, O+ , Ar+, 13C2+, N2+ and O2+ at 4keV. The decrease in ice thickness as a function of ion dose wasmonitored by a laser interferometer and the model used to determine thesputtering yield as shown in Figure 1.In the case of O2 ice thesputtering yields increased with increasing ion mass in good agreementwith a model calculation [Fama, J, Shi, R.A Baragiola, Surface Sci.,602, 156 (2007)]. In the case of O2 ice, O2+ has a significant lowersputtering yield when compared to O+. The sputtering yields for O2 icewere found to be at least 9 times larger compared to those for H2O ice.For H2O ice the sputter yields for C, N and O ions were found todecrease with increasing mass. Doubly charged C, N and O ions which werefound to have the same sputtering yield as the singly charged ionswithin the experimental errors. A preliminary TPD study was carried outusing a QMS to detect the desorbed species from water ice afterirradiation by 6 × 10^15 ions of 13C+ and 13C2+. The formation of13CO and 13CO2 was observed with the yield of 13CO almost of a factor of100 larger than of 13CO2. This is in contrast to our earlier work whereonly CO¬2 was observed.

Exploring molecular recognition pathways within a family of gelators with different hydrogen bonding motifs

We report the synthesis of a family of gelators in which alkyl chains are connected to the amino groups of L-lysine methyl ester using a range of different hydrogen bonding linking groups (carbamate, amide, urea, thiourea and diacylhydrazine) using simple synthetic methodology based on isocyanate or acid chloride chemistry. The ability of these compounds to gelate organic solvents such as toluene or cyclohexane can be directly related to the ability of the linking group to form intermolecular hydrogen bonds. In general terms, the ability to structure solvents can be considered as: thiourea <carbamate <amide <urea similar to diacylhydrazine. This process has been confirmed by thermal measurements, scanning electron microscopy (SEM) and infrared and circular dichroism spectroscopies. By deprotecting the methyl ester group, we have demonstrated that a balance between hydrophobic and hydrophilic groups is essential-if the system has too much hydrophilicity (e. g., diacylhydrazine, urea) it will not form gels due to low solubility in the organic media. However, the less effective gelators based on amide and carbamate linkages are enhanced by converting the methyl ester to a carboxylic acid. Furthermore, subsequent mixing of the acid with a second component (diaminododecane) further enhances the ability to form networks, and, in the case of the amide, generates a two-component gel, which can immobilise a wide range of solvents of industrial interest including petrol and diesel (fuel oils), olive oil and sunflower oil (renewable food oils) and ethyl laurate, isopropyl myristate and isopropyl palmitate (oils used in pharmaceutical formulation). The gels are all thermoreversible, and may therefore be useful in controlled release/formulation applications.

Design and physicochemical characterisation of novel dissolving polymeric microneedle arrays for transdermal delivery of high dose, low molecular weight drugs

We describe formulation and evaluation of novel dissolving polymeric microneedle (MN) arrays for the facilitated delivery of low molecular weight, high dose drugs. Ibuprofen sodium was used as the model here and was successfully formulated at approximately 50% w/w in the dry state using the copolymer poly(methylvinylether/maleic acid). These MNs were robust and effectively penetrated skin in vitro, dissolving rapidly to deliver the incorporated drug. The delivery of 1.5mg ibuprofen sodium, the theoretical mass of ibuprofen sodium contained within the dry MN alone, was vastly exceeded, indicating extensive delivery of the drug loaded into the baseplates. Indeed in in vitro transdermal delivery studies, approximately 33mg (90%) of the drug initially loaded into the arrays was delivered over 24h. Iontophoresis produced no meaningful increase in delivery. Biocompatibility studies and in vivo rat skin tolerance experiments raised no concerns. The blood plasma ibuprofen sodium concentrations achieved in rats (263μgml(-1) at the 24h time point) were approximately 20 times greater than the human therapeutic plasma level. By simplistic extrapolation of average weights from rats to humans, a MN patch design of no greater than 10cm(2) could cautiously be estimated to deliver therapeutically-relevant concentrations of ibuprofen sodium in humans. This work, therefore, represents a significant progression in exploitation of MN for successful transdermal delivery of a much wider range of drugs.

Mass enhances speed but diminishes turn capacity in terrestrial pursuit predators

The dynamics of predator-prey pursuit appears complex, making the development of a framework explaining predator and prey strategies problematic. We develop a model for terrestrial, cursorial predators to examine how animal mass modulates predator and prey trajectories and affects best strategies for both parties. We incorporated the maximum speed-mass relationship with an explanation of why larger animals should have greater turn radii; the forces needed to turn scale linearly with mass whereas the maximum forces an animal can exert scale to a 2/3 power law. This clarifies why in a meta-analysis, we found a preponderance of predator/prey mass ratios that minimized the turn radii of predators compared to their prey. It also explained why acceleration data from wild cheetahs pursuing different prey showed different cornering behaviour with prey type. The outcome of predator prey pursuits thus depends critically on mass effects and the ability of animals to time turns precisely.

Molecular markers in the treatment of metastatic colorectal cancer

Although significant progress has been made in colorectal cancer (CRC) treatment within the last decade with the approval of multiple new agents, the prognosis for patients with metastatic CRC remains poor with 5-year survival rates of approximately 8%. Resistance to chemotherapy remains a major obstacle in effective CRC treatment and many patients do not receive any clinical benefit from chemotherapy. In addition, other patients will experience adverse reactions to treatment resulting in dose modifications or treatment withdrawal, which can severely reduce treatment efficacy. Currently, significant research efforts are attempting to identify reliable and validated biomarkers with which will guide clinicians to make more informed treatment decisions. Specifically, the use of molecular profiling has the potential to assist the clinician in administering the correct drug, dose, or intervention for the patient before the onset of therapy thereby selecting a treatment strategy likely to have the greatest clinical outcome while minimizing adverse events. However, until recently, personalized medicine is a paradigm that has existed more in conceptual terms than in reality with very few validated biomarkers used routinely in metastatic CRC treatment. Rapid advances in genomic, transcriptomic and proteomic technologies continues to improve our understanding of tumor biology, but the search for reliable biomarkers has turned out to be more challenging than previously anticipated with significant disparity in published literature and limited translation into routine clinical practice. Recent progress with the identification and validation of biomarkers to the anti-epidermal growth factor receptor monoclonal antibodies including KRAS and possibly BRAF provide optimism that the goal of individualized treatment is within reach. This review will highlight and discuss current progress in the search for biomarkers, the challenges this emerging field presents, and the future role of biomarkers in advancing CRC treatment.

Molecular predictors of response to antiangiogenesis therapies

Angiogenesis is a crucial component of tumor growth and metastasis. Targeting the vascular endothelial growth factor pathway represents therapeutic potentials for treating cancer. To date, 3 Food and Drug Administration-approved agents targeting angiogenesis have been developed, bevacizumab, sunitinib, and sorafenib. However, no validated biomarkers are available to identify those patients who are likely to benefit from antiangiogenesis therapy. Molecular biomarker research in antiangiogenesis inhibition is an actively growing field. Although current data are extremely promising, it is still uncertain which biomarker(s) can reliably predict their efficacy. With increasing numbers of inhibitors being developed, the need for biomarkers is more critical than ever. This review will focus on translational research that strives to identify molecular biomarkers (tissue, circulating and genomic) for approved antiangiogenesis therapies that can indicate benefit, resistance, and toxicity.