Genome-wide association study of prostate cancer-specific survival

BACKGROUND: Unnecessary intervention and overtreatment of indolent disease are common challenges in clinical management of prostate cancer. Improved tools to distinguish lethal from indolent disease are critical. METHODS: We performed a genome-wide survival analysis of cause-specific death in 24,023 prostate cancer patients (3,513 disease-specific deaths) from the PRACTICAL and BPC3 consortia. Top findings were assessed for replication in a Norwegian cohort (CONOR). RESULTS: We observed no significant association between genetic variants and prostate cancer survival. CONCLUSIONS: Common genetic variants with large impact on prostate cancer survival were not observed in this study. IMPACT: Future studies should be designed for identification of rare variants with large effect sizes or common variants with small effect sizes.

Synthesis of 19F nucleic acid–polymer conjugates as real-time MRI probes of biorecognition

Polymer-DNA conjugates in which one nucleic acid strand contains fluorine-substituted nucleobases have been prepared and characterised. The efficacy of these novel F-19 nucleic acid-polymer conjugates as sensitive and selective in vitro reporters of DNA binding events is demonstrated through a number of rapid-acquisition MR sequences. The conjugates respond readily and in a sequence specific manner to external target oligonucleotide sequences by changes in hybridisation. In turn, these structural changes in polymer-nucleotide conjugates translate into responses which are detectable in fluorine relaxation and diffusion switches, and which can be monitored by in vitro Spin Echo and DOSY NMR spectroscopy. Although complementary to conventional FRET methods, the excellent diagnostic properties of fluorine nuclei make this approach a versatile and sensitive probe of molecular structure and conformation in polymeric assemblies.

Two ex situ fungal technologies to treat contaminated soil

Wood-degrading fungi are able to degrade a large range of recalcitrant pollutants which resemble the lignin biopolymer. This ability is attributed to the production of lignin-modifying enzymes, which are extracellular and non-specific. Despite the potential of fungi in bioremediation, there is still an understanding gap in terms of the technology. In this thesis, the feasibility of two ex situ fungal bioremediation methods to treat contaminated soil was evaluated. Treatment of polycyclic aromatic hydrocarbons (PAHs)-contaminated marsh soil was studied in a stirred slurry-phase reactor. Due to the salt content in marsh soil, fungi were screened for their halotolerance, and the white-rot fungi Lentinus tigrinus, Irpex lacteus and Bjerkandera adusta were selected for further studies. These fungi degraded 40 - 60% of a PAH mixture (phenanthrene, fluoranthene, pyrene and chrysene) in a slurry-phase reactor (100 ml) during 30 days of incubation. Thereafter, B. adusta was selected to scale-up and optimize the process in a 5 L reactor. Maximum degradation of dibenzothiophene (93%), fluoranthene (82%), pyrene (81%) and chrysene (83%) was achieved with the free mycelium inoculum of the highest initial biomass (2.2 g/l). In autoclaved soil, MnP was the most important enzyme involved in PAH degradation. In non-sterile soil, endogenous soil microbes together with B. adusta also degraded the PAHs extensively, suggesting a synergic action between soil microbes and the fungus. A fungal solid-phase cultivation method to pretreat contaminated sawmill soil with high organic matter content was developed to enhance the effectiveness of the subsequent soil combustion. In a preliminary screening of 146 fungal strains, 28 out of 52 fungi, which extensively colonized non-sterile contaminated soil, were litter-decomposing fungi. The 18 strains further selected were characterized by their production of lignin-modifying and hydrolytic enzymes, of which MnP and endo-1,4-β-glucanase were the main enzymes during cultivation on Scots pine (Pinus sylvestris) bark. Of the six fungi selected for further tests, Gymnopilus luteofolius, Phanerochaete velutina, and Stropharia rugosoannulata were the most active soil organic matter degraders. The results showed that a six-month pretreatment of sawmill soil would result in a 3.5 - 9.5% loss of organic matter, depending on the fungus applied. The pretreatment process was scaled-up for a 0.56 m3 reactor, in which perforated plastic tubes filled with S. rugosoannulata growing on pine bark were introduced into the soil. The fungal pretreatment resulted in a soil mass loss of 30.5 kg, which represents 10% of the original soil mass (308 kg). Despite the fact that Scots pine bark contains several antimicrobial compounds, it was a suitable substrate for fungal growth and promoter of the production of oxidative enzymes, as well as an excellent and cheap natural carrier of fungal mycelium. This thesis successfully developed two novel fungal ex situ bioremediation technologies and introduce new insights for their further full-scale application. Ex situ slurry-phase fungal reactors might be applied in cases when the soil has a high water content or when the contaminant bioavailability is low; for example, in wastewater treatment plants to remove pharmaceutical residues. Fungal solid-phase bioremediation is a promising remediation technology to ex situ or in situ treat contaminated soil.

Expected Performance of the ATLAS Experiment - Detector, Trigger and Physics

A detailed study is presented of the expected performance of the ATLAS detector. The reconstruction of tracks, leptons, photons, missing energy and jets is investigated, together with the performance of b-tagging and the trigger. The physics potential for a variety of interesting physics processes, within the Standard Model and beyond, is examined. The study comprises a series of notes based on simulations of the detector and physics processes, with particular emphasis given to the data expected from the first years of operation of the LHC at CERN.

Organometallic chemistry of diphosphazanes *1: VIII. Synthesis, spectroscopic studies and crystal structure of fac-[Mo(CO)3(MeCN)Ph2PN(iPr)P(Ph)(DMP)], and its reactions with tertiary phosphines

The reaction of fac-[Mo(CO)3(MeCN)3] with the unsymmetrical diphosphazane Ph2PN(iPr)P(Ph)(DMP) (L) gives the complex fac-[Mo(CO)3(MeCN)(L)] (2) in almost quantitative yield. The structure of the complex has been determined by an X-ray diffraction study. The compound reacts with PR3 (where R = Ph, OPh) to give fac-[Mo(CO)3(PR3)(L)] (3a, 4a), which undergoes an intramolecular isomerization to afford mer-[Mo(CO)3(PR3)(L)] (3b, 4b). Synthesis of cis-[Mo(CO)4(L)] (1) and fac-[MO(CO)3L] (2a) and their spectroscopic data are also reported.

Synthesis, properties and crystal structures of diastereomeric areneruthenium(II) chiral Schiff-base complexes

Diastereomers (SRu,Sc)-1a and (RRu,Sc)-1b, in a ratio of 85: 15 and formulated as [Ru(η-MeC6H4Pri-p)Cl(L*)], have been prepared by treating [{Ru(η-MeC6H4Pri-p)Cl2}2] with the sodium salt of (S)-α-methylbenzylsalicylaldimine (HL*) in tetrahydrofuran at –70 °C. The reaction of 1(1a+1b) with AgClO4 in acetone followed by an addition of PPh3 or 4-methylpyridine (4Me-py) leads to the formation of adducts [Ru(η-MeC6H4Pri-p)(PPh3)(L*)]ClO42[(SRu,Sc)2a, (FRu,Sc)2b] and [Ru(η-MeC6H4Pri-p)(4Me-py)(L*)]ClO43[(SRu,Sc)3a, (RRu,Sc)3b] in the diastereomeric ratios (SRu,Sc) : (RRu,Sc) of 2 : 98 and 76 : 24, respectively. Complex 1 crystallises with equal numbers of 1a and 1b molecules in an asymmetric unit of monoclinic space group P21 with a= 10.854(1), b= 17.090(1), c= 12.808(4)Å, β= 110.51(1)°, and Z= 4. The structure was refined to R= 0.0552 and R′= 0.0530 with 2893 reflections having I[gt-or-equal] 1.5σ(I). The absolute configurations of the chiral centres in the optically pure single crystal of the PPh3 adduct have been obtained from an X-ray study. Crystals of formulation [Ru(η-MeC6H4Pri-p)-(PPh3)(L*)]2[ClO4][PF6]·1.5 CHCl3, obtained in presence of both ClO4 and PF6 anions, belong to the non-centric triclinic space group P1 with a= 10.852(2), b= 14.028(1), c= 15.950(2)Å, α= 91.51(1), β= 105.97(1), γ= 106.11(1)°, and Z= 2. The final residuals were R= 0.0713, R′= 0.0752 with 7283 reflections having I[gt-or-equal] 2.5σ(I). The crystal structures of 1a,1b, and the PPh3 adduct (2b,2b′) consist of a ruthenium(II) centre bonded to a η-p-cymene, a bidentate chelating Schiff base, and a unidentate ligand (Cl or PPh3). The chirooptical properties of the complexes have been studied using 1H NMR and CD spectral data. The presence of a low-energy barrier for the intermediate involved in these reactions, showing both retention as well as inversion of the metal configuration, is discussed.

Coordination-driven self-assembly of 2D-metallamacrocycles using a shape-selective Pt(2)(II)-organometallic 90 degrees acceptor: design, synthesis and sensing study

Synthesis of a series of two-dimensional metallamacrocycles via coordination-driven self-assembly of a shape-selective Pt(2)(II)-molecular building unit incorporating carbazole-ethynyl functionality is described. An equimolar (1 : 1) combination of a Pt(2)(II)-organometallic 90 degrees acceptor, 1, with rigid linear ditopic donors (L(a) and L(b)) afforded [4 + 4] self-assembled octanuclear molecular squares, 2 and 3, in quantitative yields, respectively [L(a) = 4,4'-bipyridine; L(b) = trans-1,2-bis(4-pyridyl)ethylene]. Conversely, a similar treatment of 1 with an amide-based unsymmetrical flexible ditopic donor, L(c), resulted in the formation of a [2 + 2] self-sorted molecular rhomboid (4a) as a single product [L(c) = N-(4-pyridyl)isonicotinamide]. Despite the possibility of several linkage isomeric macrocycles (rhomboid, triangle and square) due to the different connectivity of L(c), the formation of a single and symmetrical molecular rhomboid (4a) as the only product is an interesting observation. All the self-assembled macrocycles (2, 3 and 4a) were fully characterized by multinuclear NMR ((1)H and (31)P) and ESI-MS analysis. Further structural insights about the size and shape of the macrocycles were obtained through energy minimization using density functional theory (DFT) calculations. Decoration of the starting carbazole building unit with Pt-ethynyl functionality enriches the assemblies to be more p-electron rich and luminescent in nature. Macrocycles 2 and 3 could sense the presence of electron deficient nitroaromatics in solution by quenching of the initial intensity upon gradual addition of picric acid (PA). They exhibited the largest quenching response with high selectivity for nitroaromatics compared to several other electron deficient aromatics tested.

Power Controlled Reverse Channel Training Achieves an Infinite Diversity Order in a TDD-SIMO System with Perfect CSIR

In this letter, we analyze the Diversity Multiplexinggain Tradeoff (DMT) performance of a training-based reciprocal Single Input Multiple Output (SIMO) system. Assuming Channel State Information (CSI) is available at the Receiver (CSIR), we propose a channel-dependent power-controlled Reverse Channel Training (RCT) scheme that enables the transmitter to directly estimate the power control parameter to be used for the forwardlink data transmission. We show that, with an RCT power of (P) over bar (gamma), gamma > 0 and a forward data transmission power of (P) over bar, our proposed scheme achieves an infinite diversity order for 0 <= g(m) < L-c-L-B,L-tau/L-c min(gamma, 1) and r > 2, where g(m) is the multiplexing gain, L-c is the channel coherence time, L-B,L-tau is the RCT duration and r is the number of receive antennas. We also derive an upper bound on the outage probability and show that it goes to zero asymptotically as exp(-(P) over bar (E)), where E (sic) (gamma - g(m)L(c)/L-c-L-B,L-tau), at high (P) over bar. Thus, the proposed scheme achieves a significantly better DMT performance compared to the finite diversity order achieved by channel-agnostic, fixed-power RCT schemes.

Coordination self-assembly of tetranuclear Pt(II) macrocycles with an organometallic backbone for sensing of acyclic dicarboxylic acids

Coordination self-assembly of a series of tetranuclear Pt(II) macrocycles containing an organometallic backbone incorporating ethynyl functionality is presented. The 1 : 1 combination of a linear acceptor 1,4-bistrans-Pt(PEt3)(2)(NO3)(ethynyl)]benzene (1) with three different dipyridyl donor `clips' (L-a-L-c) afforded three 2 + 2] self-assembled Pt-4(II) macrocycles (2a-2c) in quantitative yields, respectively L-a = 1,3-bis-(3-pyridyl)isothalamide; L-b = 1,3-bis(3-pyridyl)ethynylbenzene; L-c = 1,8-bis(4-pyridyl)ethynylanthracene]. These macrocycles were characterized by multinuclear NMR (H-1 and P-31); ESI-MS spectroscopy and the molecular structures of 2a and 2b were established by single crystal X-ray diffraction analysis. These macrocycles (2a-2c) are fluorescent in nature. The amide functionalized macrocycle 2a is used as a receptor to check the binding affinity of aliphatic acyclic dicarboxylic acids. Such binding affinity is examined using fluorescence and UV-Vis spectroscopic methods. A solution state fluorescence study showed that macrocycle 2a selectively binds (K-SV = 1.4 x 10(4) M-1) maleic acid by subsequent enhancement in emission intensity. Other aliphatic dicarboxylic acids such as fumaric, succinic, adipic, mesaconic and itaconic acids caused no change in the emission spectra; thereby demonstrating its potential use as a macrocyclic receptor in distinction of maleic acid from other aliphatic dicarboxylic acids.

Expression and function of cyclooxygenase-2 is necessary for hamster blastocyst hatching

Blastocyst hatching is critical for successful implantation leading to pregnancy. Its failure causes infertility. The phenomenon of blastocyst hatching in humans is poorly understood and the available information on this stems from studies of rodents such as mice and hamsters. We and others showed that hamster blastocyst hatching is characterized by firstly blastocyst deflation followed by a dissolution of the zona pellucida (zona) and accompanied by trophectodermal projections (TEPs). We also showed that embryo-derived cathepsins (Cat) proteases, specifically Cat-L, -B and -P act as zonalysins and are responsible for hatching. In this study, we show the expression and function of one of the potential regulators of embryogenesis, cyclooxygenase (COX)-2 during blastocyst development and hatching. The expression of COX-2 mRNA and protein was observed in 8-cell through hatched blastocyst stages and it was also localized to blastocysts TEPs. Specific COX-2 inhibitors, NS-398 and CAY-10404, inhibited blastocyst hatching; percentages achieved were only 28.4 5.3 and 32.3 5.4, respectively, compared with 90 with untreated embryos. Interestingly, inhibitor-treated blastocysts failed to deflate, normally observed during hatching. Supplementation of prostaglandins (PGs)-E-2 or -I-2 to cultured embryos reversed the inhibitors effect on hatching and also the deflation behavior. Importantly, the levels of mRNA and protein of Cat-L, -B and -P showed a significant reduction in the inhibitor-treated embryos compared with untreated embryos, although its mechanism remains to be examined. These data provide the first evidence that COX-2 is critical for blastocyst hatching in the golden hamster.

Kinetics and Force Dependence of P-selectin/PSGL-1 Interactions Measured by AFM

Leukocytes roll along the endothelium of postcapillary venules in response to inflammatory and thrombotic processes. The rolling under hydrodynamic shear forces is a first step in directing leukocytes out of the blood stream into sites of inflammation and is mediated by the selectins, a family of extended, modular, and calcium-dependent lectin receptors. The interactions between P-, E-or L-selectins and their count.

Stainless steel sandwich

The Cambridge University's Gordon Laboratory, in collaboration with Fibertech and the Defence Science and Technology Laboratory in the UK, has developed a novel melt spun fiber bore called 'Fibrecore', fabricated entirely from stainless steel with thin faceplates. Fibrecore is typically manufactured by 5mm-long and 70μm thick stainless steel fibers, produced by a melt overflow process. Its entirely metallic construction allows spot welding and tungsten inert gas welding without difficulty. Fibrecore exhibits different energy absorption mechanisms such as core cushioning, core-faceplate delamination, and plastic faceplate deformation, often in a concertina-like fashion. Its low-cost, high structural efficiency and good energy absorption characteristics make it attractive for a range of commercial and military applications. Such applications being evaluated include vehicle body panels, exhaust system noise reduction, low cost filters, and lightweight physical protection. In addition to these characteristics, Fibrecore exhibits properties such as corrosion protection, vibrational damping, and thermal insulation, which also extend its applications.

Electrical and field emission investigation of individual carbon nanotubes from plasma enhanced chemical vapour deposition

Plasma enhanced chemical vapour deposition (PECVD) is a controlled technique for the production of vertically aligned multiwall carbon nanotubes for field emission applications. In this paper, we investigate the electrical properties of individual carbon nanotubes which is important for designing field emission devices. PECVD nanotubes exhibit a room temperature resistance of 1-10 kΩ/μm length (resistivity 10-6 to 10-5 Ω m) and have a maximum current carrying capability of 0.2-2 mA (current density 107-108 A/cm2). The field emission characteristics show that the field enhancement of the structures is strongly related to the geometry (height/radius) of the structures and maximum emission currents of ∼ 10 μA were obtained. The failure of nanotubes under field emission is also discussed. © 2002 Elsevier Science B.V. All rights reserved.

Influence of shelf-break fronts on shellfish and fish stocks off Argentina [Contribution to ICES Annual Science Conference, Reykjavik, Iceland, 27 Sep- 04 Oct 1996]

The general circulation pattern in the western boundary of the SW Atlantic is dominated by the opposite flows of Malvinas (-Falkland)and Brazil Current. In the Confluence region both currents separate from the continental slope and flow offshore creating an area of strong contracts and complex dynamics. The shelf-break fronts off Argentina mark the transition between shelf waters of mixed origin and nutrient rich Malvinas waters. Two areas deserve special attention due to the steep gradients introduced by the outflow of important sources of continental waters: the Rio de la Plata and the Magellan Strait to the north and south of the study area. Characteristics of the front is the high primary and secondary production, and the presence of important invertebrate and fish stocks that concentrate along the front to feed or spawn. The area comprises nearly 30 o/o (333 million U$S in 1995)of all Argentine catches of fish and squid. Resources in the area, beyond the EEZ limits, support international fisheries mainly of Russia, Poland and Spain. (Document contains 15 pages & figs)