Covalent binding studies on the 14C-labeled antitumour compound 2,5-bis(1-aziridinyl)-1,4-benzoquinone. Involvement of semiquinone radical in binding to DNA, and binding to proteins and bacterial macromolecules in situ

2,5-Bis(1-aziridinyl)-1,4-benzoquinone (BABQ) is a compound from which several antitumour drugs are derived, such as Trenimone, Carboquone and Diaziquone (AZQ). The mechanism of DNA binding of BABQ was studied using 14C-labeled BABQ and is in agreement with reduction of the quinone moiety and protonation of the aziridine ring, followed by ring opening and alkylation. The one-electron reduced (semiquinone) form of BABQ alkylates DNA more efficiently than two-electron reduced or non reduced BABQ. Covalent binding to polynucleotides did not unambiguously reveal preference for binding to specific DNA bases. Attempts to elucidate further the molecular structure of DNA adducts by isolation of modified nucleosides from enzymatic digests of reacted DNA failed because of instability of the DNA adducts. The mechanism of covalent binding to protein (bovine serum albumin, BSA) appeared to be completely different from that of covalent binding to DNA. Binding of BABQ to BSA was not enhanced by reduction of the compound and was pH dependent in a way that is opposite to that of DNA alkylation. Glutathione inhibits binding of BABQ to BSA and forms adducts with BABQ in a similar pH dependence as the protein binding. The aziridine group therefore does not seem to be involved in the alkylation of BSA. Incubation of intact E. coli cells, which endogenously reduce BABQ, resulted in binding to both DNA and RNA, but also appreciable protein binding was observed

Imaging dielectric relaxation in nanostructured polymers by frequency modulation electrostatic force microscopy

We have developed a method for imaging the temperature-frequency dependence of the dynamics of nanostructured polymer films with spatial resolution. This method provides images with dielectric compositional contrast well decoupled from topography. Using frequency-modulation electrostatic-force-microscopy, we probe the local frequency-dependent (0.1–100 Hz) dielectric response through measurement of the amplitude and phase of the force gradient in response to an oscillating applied electric field. When the phase is imaged at fixed frequency, it reveals the spatial variation in dielectric losses, i.e., the spatial variation in molecular/dipolar dynamics, with 40 nm lateral resolution. This is demonstrated by using as a model system; a phase separated polystyrene/polyvinyl-acetate (PVAc) blend. We show that nanoscale dynamic domains of PVAc are clearly identifiable in phase images as those which light-up in a band of temperature, reflecting the variations in the molecular/dipolar dynamics approaching the glass transition temperature of PVAc

Mitosene-DNA adducts. Characterization of two major DNA monoadducts formed by 1,10-bis(acetoxy)-7-methoxymitosene upon reductive activation

Reductive activation of racemic 1,10-bis(acetoxy)-7-methoxymitosene WV15 in the presence of DNA, followed by enzymatic digestion and HPLC analysis, revealed the formation of various DNA adducts. Reduction is a necessary event for adduct formation to occur. This reductive activation was performed under hypoxic conditions in various ways:  (1) chemically, using a 2-fold excess of sodium dithionite (Na2S2O4), (2) enzymatically using NADH-cytochrome c reductase, (3) electrochemically on a mercury pool working electrode, and (4) catalytically, using a H2/PtO2 system. Five different mitosene−DNA adducts were detected. These adducts were also present when poly(dG-dC) was used instead of DNA, but were absent with poly(dA-dT). All were shown to be adducts of guanine. Reduction of 1,10-dihydroxymitosene WV14 in the presence of DNA did not result in detectable adduct formation, demonstrating the importance of good leaving groups for efficient adduct formation by these mitosenes. Finally, two of the adducts were isolated and their structures elucidated, using mass spectrometry, 1H NMR and circular dichroism (CD). The structures were assigned as the diastereoisomers N2-(1‘ ‘-n-hydroxymitosen-10‘ ‘-yl), 2‘-deoxyguanosine (n = α or β). These type of adducts, in which the mitosene C-10 is covalently bonded to the N-2 of a guanosylic group, are different from the well-known mitomycin C 2‘-deoxyguanosine monoadducts, that is linked via the mitomycin C C-1 position, demonstrating that the order of reactivity of the C-1 and C-10 in these mitosenes is reversed, as compared to mitomycin C. The 7-methoxy substituent of WV15 is a likely factor causing this switch. Evidence is presented that the 7-substituent of mitosenes also influences their DNA alkylation site. Adducts 4 and 5 represent the first isolated and structurally characterized covalent adducts of DNA and a synthetic mitosene

Влияние условий синтеза на размер наночастиц железа

Показана возможность получения наночастиц железа разного размера путем варьирования условий синтеза. Методами электронной микроскопии, ИК спектроскопии и электронной дифракции изучена их морфология и структура. Установлено, что при нанесении наночастиц железа на угольный носитель размер, распределение и строение частиц не меняется.Показана можливість отримання наночастинок заліза різного розміру шляхом варіювання умов синтезу. Методами електронної мікроскопії, ІЧ спектроскопії та електронної дифракції вивчено їх морфологію та структуру. Знайдено, що при нанесенні наночастинок заліза на носії розмір, розподіл та будова не змінюється.The preparation of monodisperse Fe nanoparticles of various sizes by varying synthesis conditions is reported. Nanoparticles have been studied by transmission electron microscopy, IR spectroscopy, and electron diffraction. It was shown that Fe nanoparticles do not change its size, distribution, and structure after impregnation of support

Sedimentological study of cold-water coral mounds on Pen Duick Escarpment (Gulf of Cadiz): preliminary results of the MD169 cruise

Cold-water corals are widely distributed along the Moroccan margin in the Northeast Atlantic Ocean. Within the Gulf of Cadiz mud volcanoes, submarine ridges and steep fault escarpments occur, which favour the settlement of scleractinians and build up coral mounds. One of these sites is the Pen Duick Escarpment, situated in the El Arraiche mud volcano field, 35 km offshore the city of Larache. Pen Duick Escarpment is a 6 km long, SSE-NNW oriented, 80 to 125 m high wall with a southwest-facing slope of 8 to 12°. Up to now, 15 coral mounds were recognized on top of the escarpment with an average estimated elevation of 15 m. Although cold-water corals are a common feature on the adjacent cliffs, mud volcanoes and seafloor, no actual living coral has been observed.This study is based upon three on-mound gravity cores (Alpha, Beta and Gamma mound) acquired by R/V Marion Dufresne in 2008 (MD169). Each mound was cored at least twice to recover both a core for biogeochemical and microbial studies, and another core for sedimentological purposes, in order to link both processes. The sedimentological cores were analysed using different techniques (medical CT scanning, XRF, U/Th dating, stable isotopes, grain-size analysis) in order to obtain a holistic view on the build-up of a mound. The coring, together with present-day seabed observations, revealed the architectural importance of open coral rubble plates in the role of mound building. These graveyards act not only as sediment trap but also as microhabitat for a wide range of benthic organisms

Northeastern Atlantic cold-water coral reefs and climate

U-series age patterns obtained on reef framework-forming cold-water corals collected over a nearly 6,000 km long continental margin sector, extending from off Mauritania to the south-western Barents Sea reveal strong climate influences on the geographical distribution and sustained development of these ecosystems. During glacial times densely populated cold-water coral reefs flourished in the temperate east Atlantic, where at present only scarce live coral occurrences exist. In contrast, climate warming induces a rapid northward colonization of cold-water coral reefs with the biogeographic limit advancing from ~45°N to ~70°N. Thus, we invoke here that north-south oscillations of the polar front during the past glacial-interglacial cycles and the consequent displacement of cold nutrient-rich intermediate waters and productivity drives the decline and expansion of cold-water coral ecosystems and its biogeographic limits in the northeast Atlantic

So you call that research? : mending methodological biases in strategy and organization departments of top business schools

We believe that all strategy and organization (SO) scholars should be able to decide for themselves whether to specialize in certain parts of the knowledge cycle or adopt a broader, multi-method view on the scientific process. In a situation of ―methodological pluralism‖, individuals might choose to contribute to the construction of new administrative theories by means of qualitative works like case studies, ethnographies, biographies, or grounded theory studies (e.g., see Denzin and Lincoln, 2000). Others could then specialize in testing these theories by means of experiments, surveys, or longitudinal econometric studies (e.g., see Lewis-Beck, 1987-2004). Again others could combine both approaches in Herculean attempts to conduct high-impact, integrative research with the potential to change the way we understand the field as a whole

Consequences of cervical pessary for subsequent pregnancy : follow-up of randomized clinical trial (ProTWIN)

Funding Information: B.W.M. is supported by a NHMRC Investigator grant (GNT1176437). B.W.M. reports consultancy for ObsEva and has received research funding from Guerbet, Ferring and Merck. The original ProTWIN trial was funded by ZonMW grant 200310004. We did not receive any funding for this follow‐up research.Peer reviewedPublisher PD

Dislocation loops in overheated free-standing smectic films

Static and dynamic phenomena in overheated free-standing smectic-A films are studied using a generalization of de Gennes' theory for a confined presmectic liquid. A static application is to determine the profile of the film meniscus and the meniscus contact angle, the results being compared with those of a recent study employing de Gennes' original theory. The dynamical generalization of the theory is based on on a time-dependent Ginzburg-Landau approach. This is used to compare two modes for layer-thinning transitions in overheated films, namely "uniform thinning" vs. nucleation of dislocation loops. Properties such as the line tension and velocity of a moving dislocation line are evaluated self-consistently by the theory.Comment: 16 pages, 8 figure