Group 6 carbene complexes derived from lithiated azoles and the crystal structure of a molybdenum thiazolinylidene complex

Fischer-type (alkoxy)azolyl carbene complexes and Ofele-Lappert-type azolylinylidene complexes were synthesised by reaction of 1-phenylpyrazol-3 -yllithium, 4-methylthiazol-2-yllithium, benzothiazol-2-yllithium, 1-methylimidazol-2-yllithium with M(CO)(5)L (L = CO, THF or Cl-; M = Cr, Mo or W) and subsequent alkylation with CF3SO3CH3. The alkylation of Fischer-type carbene complexes containing an azolyl as the organic substituent proceeded via ring opening of tetrahydrofuran. When the alkylation is carried out in THF, the carbocation CH3O(CH2)(4)(+) acts as an electrophile. Protonation rather than alkylation of coordinated imidazolyl furnished cyclic imine complexes. Changing the donor atom of a coordinated thiazole from N to C by deprotonation and alkylation afforded a carbene complex. (C) 1999 Elsevier Science S.A. All rights reserved.

One-pot two-step mechanochemical synthesis: ligand and complex preparation without isolating intermediates

Although the use of ball milling to induce reactions between solids (mechanochemical synthesis) can provide lower-waste routes to chemical products by avoiding solvent during the reaction, there are further potential advantages in using one-pot multistep syntheses to avoid the use of bulk solvents for the purification of intermediates. We report here two-step syntheses involving formation of salen-type ligands from diamines and hydroxyaldehydes followed directly by reactions with metal salts to provide the corresponding metal complexes. Five salen-type ligands 2,2'-[1,2-ethanediylbis[(E)-nitrilomethylidyne]] bisphenol, ` salenH2', 1; 2,2'-[(+/-)-1,2-cyclohexanediylbis-[(E)-nitrilomethylidyne]] bis-phenol, 2; 2,2'-[1,2-phenylenebis( nitrilomethylidyne)]-bis-phenol, ` salphenH2' 3; 2-[[(2-aminophenyl) imino] methyl]-phenol, 4; 2,2'-[(+/-)-1,2-cyclohexanediylbis[(E)-nitrilomethylidyne]]-bis[4,6-bis(1,1-dimethylethyl)]-phenol, ` Jacobsen ligand', 5) were found to form readily in a shaker-type ball mill at 0.5 to 3 g scale from their corresponding diamine and aldehyde precursors. Although in some cases both starting materials were liquids, ball milling was still necessary to drive those reactions to completion because precipitation of the product and or intermediates rapidly gave in thick pastes which could not be stirred conventionally. The only ligand which required the addition of solvent was the Jacobsen ligand 5 which required 1.75 mol equivalents of methanol to go to completion. Ligands 1-5 were thus obtained directly in 30-60 minutes in their hydrated forms, due to the presence of water by-product, as free-flowing yellow powders which could be dried by heating to give analytically pure products. The one-armed salphen ligand 4 could also be obtained selectively by changing the reaction stoichiometry to 1 : 1. SalenH(2) 1 was explored for the onepot two-step synthesis of metal complexes. In particular, after in situ formation of the ligand by ball milling, metal salts (ZnO, Ni(OAc)2 center dot 4H(2)O or Cu(OAc)(2)center dot H2O) were added directly to the jar and milling continued for a further 30 minutes. Small amounts of methanol (0.4-1.1 mol equivalents) were needed for these reactions to run to completion. The corresponding metal complexes [M(salen)] (M = Zn, 6; Ni, 7; or Cu, 8) were thus obtained quantitatively after 30 minutes in hydrated form, and could be heated briefly to give analytically pure dehydrated products. The all-at-once ` tandem' synthesis of [Zn(salen)] 6 was also explored by milling ZnO, ethylene diamine and salicylaldehyde together in the appropriate mole ratio for 60 minutes. This approach also gave the target complex selectively with no solvent needing to be added. Overall, these syntheses were found to be highly efficient in terms of time and the in avoidance of bulk solvent both during the reaction and for the isolation of intermediates. The work demonstrates the applicability of mechanochemical synthesis to one-pot multi-step strategies.

Efficient, Scalable, and Solvent-free Mechanochemical Synthesis of the OLED Material Alq(3) (q=8-Hydroxyquinolinate)

The aluminum complex Alq(3) (q = 8-hydroxyquinolinate), which has important applications in organic light-emitting diode materials, is shown to be readily synthesized as a pure phase under solvent-free mechanochemical conditions from Al(OAc)(2)OH and 8-hydroxyquinoline by ball milling. The initial product of the mechanochemical synthesis is a novel acetic acid solvate of Alq(3), and the alpha polymorph of Alq(3) is obtained on subsequent heating/desolvation of this phase. The structure of the mechanochemically prepared acetic acid solvate of Alq(3) has been determined directly from powder X-ray diffraction data and is shown to be a different polymorph from the corresponding acetic acid solvate prepared by solution-state crystallization of Alq(3) from acetic acid. Significantly, the mechanochemical synthesis of Alq(3) is shown to be fully scalable across two orders of magnitude from 0.5 to 50 g scale. The Alq(3) sample obtained from the solvent-free mechanochemical synthesis is analytically pure and exhibits identical photoluminescence behavior to that of a sample prepared by the conventional synthetic route.

Unspliced X-box-binding Protein 1 (XBP1) Protects Endothelial Cells from Oxidative Stress through Interaction with Histone Deacetylase 3

It is well-known that atherosclerosis occurs geographically at branch points where disturbed flow predisposes to the development of plaque via triggering of oxidative stress and inflammatory reactions. In this study, we found that disturbed flow activated anti-oxidative reactions via up-regulating heme oxygenase 1 (HO-1) in an X-box binding protein 1 (XBP1) and histone deacetylase 3 (HDAC3)-dependent manner. Disturbed flow concomitantly up-regulated the unspliced XBP1 (XBP1u) and HDAC3 in a vascular endothelial growth factor receptor (VEGFR) and PI3K/Akt dependent manner. The presence of XBP1 was essential for the up-regulation of HDAC3 protein. Over-expression of XBP1u and/or HDAC3 activated Akt1 phosphorylation, Nrf2 protein stabilization and nuclear translocation, and HO-1 expression. Knockdown of XBP1u decreased the basal level and disturbed flow-induced Akt1 phosphorylation, Nrf2 stabilization and HO-1 expression. Knockdown of HDAC3 ablated XBP1u-mediated effects. The mammalian target of rapamycin complex 2 (mTORC2) inhibitor, AZD2014, ablated XBP1u or HDAC3 or disturbed flow-mediated Akt1 phosphorylation, Nrf2 nuclear translocation and HO-1 expression. Neither actinomycin D nor cycloheximide affected disturbed flow-induced up-regulation of Nrf2 Protein. Knockdown of Nrf2 abolished XBP1u or HDAC3 or disturbed flow-induced HO-1 up-regulation. Co-immunoprecipitation assays demonstrated that XBP1u physically bound to HDAC3 and Akt1. The region of amino acids 201 to 323 of the HDAC3 protein was responsible for the binding to XBP1u. Double immunofluorescence staining revealed that the interactions between Akt1 and mTORC2, Akt1 and HDAC3, Akt1 and XBP1u, HDAC3 and XBP1u occurred in the cytosol. Thus, we demonstrate that XBP1u and HDAC3 exert a protective effect on disturbed flow-induced oxidative stress via up-regulation of mTORC2-dependent Akt1 phosphorylation and Nrf2-mediated HO-1 expression.

Synthesis of the C(7)-C(22)-Sector of (+)-Acutiphycin Via O-Directed Double Free Radical Alkyne Hydrostannation with Ph3SnH/Et3B, Double I-Sn Exchange and Double Stille Coupling

Abstract Image

Herein a new double O-directed free radical hydrostannation reaction is reported on the structurally complex dialkyldiyne 11. Through our use of a conformation-restraining acetal to help prevent stereocenter-compromising 1,5-H-atom abstraction reactions by vinyl radical intermediates, the two vinylstannanes of 10 were concurrently constructed with high stereocontrol using Ph3SnH/Et3B/O2. Distannane 10 was thereafter elaborated into the bis-vinyl iodide 9 via O-silylation and double I–Sn exchange; double Stille coupling of 9, O-desilylation, and oxidation thereafter furnished 8.

Chromosome synapsis and recombination in simple and complex chromosomal heterozygotes of tuco-tuco (Ctenomys talarum: Rodentia: Ctenomyidae):Rodentia: Ctenomyidae)

The chromosomal speciation hypothesis suggests that irregularities in synapsis, recombination, and segregation in heterozygotes for chromosome rearrangements may restrict gene flow between karyotypically distinct populations and promote speciation. Ctenomys talarum is a South American subterranean rodent inhabiting the coastal regions of Argentina, whose populations polymorphic for Robertsonian and tandem translocations seem to have a very restricted gene flow. To test if chromosomal differences are involved in isolation among its populations, we examined chromosome pairing, recombination, and meiotic silencing of unsynapsed chromatin in male meiosis of simple and complex translocation heterozygotes using immunolocalization of the MLH1 marking mature recombination nodules and phosphorylated histone γH2A.X marking unrepaired double-strand breaks. We observed small asynaptic areas labeled by γH2A.X in pericentromeric regions of the chromosomes involved in the trivalents and quadrivalents. We also observed a decrease of recombination frequency and a distalization of the crossover distribution in the heterozygotes and metacentric homozygotes compared to acrocentric homozygotes. We suggest that the asynapsis of the pericentromeric regions are unlikely to induce germ cell death and decrease fertility of the heterozygotes; however, suppressed recombination in pericentromeric areas of the multivalents may reduce gene flow between chromosomally different populations of the Talas tuco-tuco.

Isolating Informational Masking in Both Pure and Complex Tone Sequences

Objectives: Interference between a target and simultaneous maskers occurs both at the cochlear level through energetic masking and more centrally through informational masking (IM). Hence, quantifying the amount of IM requires a strict control of the energetic component. Presenting target and maskers on different sides (i.e., dichotically) reduces energetic masking but provides listeners with important lateralization cues that also drastically reduce IM. The main purpose of this study (Experiment 1) was to evaluate a "switch" manipulation aiming at restoring most of the IM despite dichotic listening. Experiment 2 was designed to investigate the source of the difficulty induced by this switching dichotic condition.

Design: In Experiment 1, the authors presented 60 normal-hearing young adults with a detection task in which a regularly repeating target was embedded in a randomly varying background masker. The authors evaluated spatial masking release induced by three different dichotic listening conditions in comparison with a diotic baseline. Dichotic stimuli were presented in either a nonswitching or a switching condition. In the latter case, the presentation sides of dichotic target and maskers alternated several times throughout 10 sec sequences. The impact of the number of switches on IM was investigated parametrically, with both pure and complex tone sequences. In Experiment 2, the authors compared performance of 13 young, normal-hearing listeners in a monotic and dichotic version of the rapidly switching condition, using pure-tone sequences.

Results: When target and maskers switched rapidly within sequences, IM was significantly stronger than in nonswitching dichotic sequences and was comparable with the masking effect induced by diotic sequences. Furthermore, Experiment 2 suggests that rapidly switching target and maskers prevent listeners from relying on lateralization cues inherent to the dichotic condition, hence preserving important amounts of IM.

Conclusions: This paradigm thus provides an original tool to isolate IM in signal and maskers having overlapping spectra.

Factors influencing acquisition of Burkholderia cepacia complex organisms in patients with cystic fibrosis

Burkholderia cepacia complex organisms are important transmissible pathogens found in cystic fibrosis (CF) patients. In recent years, the rates of cross-infection of epidemic strains have declined due to effective infection control efforts. However, cases of sporadic B. cepacia complex infection continue to occur in some centers. The acquisition pathways and clinical outcomes of sporadic B. cepacia complex infection are unclear. We sought to determine the patient clinical characteristics, outcomes, incidence, and genotypic relatedness for all cases of B. cepacia complex infection at two CF centers. We also sought to study the external conditions that influence the acquisition of infection. From 2001 to 2011, 67 individual organisms were cultured from the respiratory samples of 64 patients. Sixty-five percent of the patients were adults, in whom chronic infections were more common (68%) (P = 0.006). The incidence of B. cepacia complex infection increased by a mean of 12% (95% confidence interval [CI], 3 to 23%) per year. The rates of transplantation and death were similar in the incident cases who developed chronic infection compared to those in patients with chronic Pseudomonas aeruginosa infection. Multilocus sequence typing revealed 50 individual strains from 65 isolates. Overall, 85% of the patients were infected with unique strains, suggesting sporadic acquisition of infection. The yearly incidence of nonepidemic B. cepacia complex infection was positively correlated with the amount of rainfall in the two sites examined: subtropical Brisbane (r = 0.65, P = 0.031) and tropical Townsville (r = 0.82, P = 0.002). This study demonstrates that despite strict cohort segregation, new cases of unrelated B. cepacia complex infection continue to occur. These data also support an environmental origin of infection and suggest that climate conditions may be associated with the acquisition of B. cepacia complex infections.

Clonal complex Pseudomonas aeruginosa in horses

Pseudomonas aeruginosa is associated with infectious endometritis in horses. Although infectious endometritis is often considered a venereal infection, there is relatively limited genotypic-based evidence to support this mode of transmission. The study sought to determine the relatedness between genital P. aeruginosa isolates collected from a limited geographical region using molecular strain typing. Enterobacterial repetitive intergenic consensus PCR typing was performed on 93 isolates collected between 2005 and 2009 from 2058 thoroughbred horses (including 18 stallions) at 66 studs. While P. aeruginosa was not detected in the stallions, 53/93 (57%) mares harbouring P. aeruginosa had clonally related strains, which included a single dominant genotype detected in 42 (45%) mares from 13 different studs. These novel findings suggest that most equine genital P. aeruginosa infections in this region may have been acquired from mechanisms other than direct horse to horse transmission. Instead, other potential acquisition pathways, as well as strain specific adaptation to the equine genital tract, should be investigated.

Disinfection of Burkholderia cepacia complex from non-touch taps in a neonatal nursery

Burkholderia cepacia complex (Bcc) comprises nine closely related species or genomovars. It is an important causative agent of opportunistic infections and waterborne nosocomial infections. B. cepacia (formerly genomovar I) was identified from the blood culture of a baby in our neonatal unit (NU) in March 2005. B. cepacia was isolated four times from clinical specimens since the introduction of non-touch taps in the NU from 2000 to 2005 and only once from 1994 to 2000. Environmental samples were collected from the NU, including tap water from non-touch taps. Clinical and environmental isolates of Bcc were characterized using molecular identification and strain typing. A literature review was undertaken to delineate a method for eradication of Bcc. Several variations for hot water eradication of the organism from the taps were attempted. Genotyping and molecular analysis revealed that tap water isolates were B. cenocepacia which was a different species from the B. cepacia isolated from blood cultures of the neonate. However, B. cenocepacia has been known to cause nosocomial outbreaks and it was eventually eradicated from the NU by using repeated thermal shock (hot water at 65 degrees C for 10 min), changing taps and decolonizing sinks with hypochlorite. Molecular typing is useful in assisting the investigation of Bcc nosocomial infections.

Burkholderia cepacia complex epidemiology in persons with cystic fibrosis from Australia and New Zealand

The Burkholderia cepacia complex (Bcc) is a group of significant opportunistic respiratory pathogens which affect people with cystic fibrosis. In this study, we sought to ascertain the epidemiology and geographic species distribution of 116 Bcc isolates collected from people with CF in Australia and New Zealand. We performed a combination of recA-based PCR, amplified rDNA restriction analysis (ARDRA), pulsed-field gel electrophoresis and repetitive extragenic palindromic PCR on each isolate. Each Burkholderia cenocepacia isolate was also screened by PCR for the presence of the B. cepacia epidemic strain marker. One hundred and fourteen isolates were assigned to a species using recA-based PCR and ARDRA. B. cenocepacia, B. multivorans and B. cepacia accounted for 45.7%, 29.3% and 11.2% of the isolates, respectively. Strain analysis of B. cenocepacia revealed that 85.3% of the isolates were unrelated. One related B. cenocepacia strain was identified amongst 15 people. Whilst full details of person-to-person contact was not available, all patients attended CF centres in Queensland (Qld) and New South Wales (NSW). Although person-to-person transmission of B. cenocepacia strains has occurred in Australia, the majority of CF-related Bcc infections in Australia and New Zealand are most likely acquired from the environment.

Genomovar diversity amongst Burkholderia cepacia complex isolates from an Australian adult cystic fibrosis unit

In this study, a combination of recA-based PCR assays and 16S rDNA restriction fragment length polymorphism (RFLP) analysis was used to determine the genomovar diversity of clinical Burkholderia cepacia complex isolates. Twenty-eight isolates were prospectively collected from patients attending a large Australian adult cystic fibrosis (CF) unit, 22 isolates were referred from other Australian CF units and a further eight isolates originated from patients without CF. The 28 prospectively collected isolates were distributed amongst the following genomovars: Burkholderia cepacia genomovar I (28.6%), Burkholderia multivorans (21.4%), Burkholderia cepacia genomovar III (39.3%), Burkholderia vietnamiensis(3.6%) and Burkholderia ambifaria (7.1%). The results of this study highlight the usefulness of 16S rDNA RFLP typing for the identification of other Burkholderia spp. and non-fermenting gram-negative bacteria.

Crime, Punishment and Article 3 ECHR: Puzzles and Prospects of Applying an Absolute Right in a Penal Context

Article 3 of the European Convention on Human Rights (ECHR), which provides that ‘No one shall be subjected to torture or to inhuman or degrading treatment or punishment’, is considered to enshrine an absolute right. Yet it contains an under-explored element: inhuman and degrading punishment. While torture has been the subject of extensive academic commentary, and inhuman and degrading treatment has been examined to some extent, the prohibition of inhuman and degrading punishment has not been explored in significant depth, in spite of its considerable potential to alter the penal landscape.

This paper elucidates the key doctrinal elements of inhuman and degrading punishment ‘and treatment associated with it’, in the words of the European Court of Human Rights (ECtHR). It addresses a number of ‘puzzles’ or problems which arise in applying the absolute right enshrined in Article 3 of the ECHR to sentencing and imprisonment, clarifies ECtHR doctrine and highlights some of its key implications. Bringing a theoretically informed understanding to bear on the application of Article 3 of the ECHR in a penal context, the paper provides clarity and coherence to a complex and crucial intersection between human rights and penology.

Coupled Effects of a Perturbation in a Complex Structure Observed with SDO/AIA, SDO/HMI and ROSA/HARDcam

We study properties of intensity fluctuations in NOAA Active Region 11250 observed on 13 July 2011 starting at UT 13:32. Included are data obtained in the EUV bands of the Atmospheric Imaging Assembly on board the Solar Dynamics Observatory (SDO/AIA) as well as nearly simultaneous observations of the chromosphere made, at much higher spatial and temporal resolution, with the Rapid Oscillations in the Solar Atmosphere (ROSA) and Hydrogen-Alpha Rapid Dynamics camera (HARDcam) systems at the Dunn Solar Telescope. A complex structure seen in both the ROSA/HARDcam and SDO data sets comprises a system of loops extending outward from near the boundary of the leading sunspot umbra. It is visible in the ROSA Ca II K and HARDcam Hα images, as well as the SDO 304 Å, 171 Å and 193 Å channels, and it thus couples the chromosphere, transition region and corona. In the ground-based images the loop structure is 4.1 Mm long. Some 17.5 Mm, can be traced in the SDO/AIA data. The chromospheric emissions observed by ROSA and HARDcam appear to occupy the inner, and apparently cooler and lower, quarter of the loop. We compare the intensity fluctuations of two points within the structure. From alignment with SDO/HMI images we identify a point "A" near the loop structure, which sits directly above a bipolar magnetic feature in the photosphere. Point "B" is characteristic of locations within the loops that are visible in both the ROSA/HARDcam and the SDO/AIA data. The intensity traces for point A are quiet during the first part of the data string. At time ~ 19 min they suddenly begin a series of impulsive brightenings. In the 171 Å and 193 Å coronal lines the brightenings are localized impulses in time, but in the transition region line at 304 Å they are more extended in time. The intensity traces in the 304 Å line for point B shows a quasi-periodic signal that changes properties at about 19 min. The wavelet power spectra are characterized by two periodicities. A 6.7 min period extends from the beginning of the series until about 25 minutes, and another signal with period ~3 min starts at about 20 min. The 193 Å power spectrum has a characteristic period of 5 min, before the 20 min transition and a 2.5 min periodicity afterward. In the case of HARDcam Hα data a localized 4 min periodicity can be found until about 7 min, followed by a quiet regime. After ~20 min a 2.3 min periodicity appears. Interestingly a coronal loop visible in the 94 Å line that is centrally located in the AR, running from the leading umbra to the following polarity, at about time 20 min undergoes a strong brightening beginning at the same moment all along 15 Mm of its length. The fact that these different signals all experience a clear-cut change at time about 20 min suggests an underlying organizing mechanism. Given that point A has a direct connection to the photospheric magnetic bipole, we conjecture that the whole extended structure is connected in a complex manner to the underlying magnetic field. The periodicities in these features may favor the wave nature rather than upflows and interpretations will be discussed.