811 research outputs found
The Dynamics of a Strongly Driven Two Component Bose-Einstein Condensate
We consider a two component Bose-Einstein condensate in two spatially localized modes of a double well potential, with periodic modulation of the tunnel coupling between the two modes. We treat the driven quantum field using a two mode expansion and define the quantum dynamics in terms of the Floquet Operator for the time periodic Hamiltonian of the system. It has been shown that the corresponding semiclassical mean-field dynamics can exhibit regions of regular and chaotic motion. We show here that the quantum dynamics can exhibit dynamical tunneling between regions of regular motion, centered on fixed points (resonances) of the semiclassical dynamics
Towards novel Au (III) porphyrins : synthesis and characterization of a range of mesotetraalkylporphyrins.
Thesis (M.Sc.)-University of KwaZulu-Natal, Pietermaritzburg, 2007.The principal goal of this work was to synthesize and fully characterize a range of fre
Synthesis and characterisation of new Schiff base chelates of platinum group metals.
Thesis (Ph.D.)-University of KwaZulu-Natal, Pietermaritzburg, 2011.The principal goal of this work was to synthesise and fully characterise a range of
platinum group metal chelates of bis(pyridine-imine) ligands. These four-nitrogen donor
Schiff base ligands are underdeveloped relative to their salen (ONNO donor)
counterparts. The purified metal complexes were to be tested for their cytotoxicity
against cancer cell lines and their mode of interaction (expected to be intercalation)
studied.
The syntheses, spectroscopic and structural properties of some novel and some already
known bis(pyridine-imine) ligands are described. Furthermore, UV-Vis, IR and NMR
spectroscopy, as well as electrospray ionisation mass spectrometry, have been used to
characterize the ligands and comparisons were made with relevant literature. Fifteen
Schiff base ligands were successfully condensed from a 2-formyl or 2-ketopyridine
starting material and a diamine bridging group, while the attempted syntheses of a
further three are described. Literature methods or variations thereof were employed in
the syntheses of these derivatives, which generally resulted in good yields. X-ray quality
crystals were obtained and X-ray structures were determined for four novel ligands and
five unexpected cyclised hexahydropyrimidine- and imidazole-containing bidentate
ligands, of which three were novel structures.
The series of bicationic palladium and platinum complexes synthesised here were
analysed by NMR, IR and UV-Vis techniques, as well as X-ray crystallography when
possible. The complexes were prepared by reacting the free ligands with platinum group
metal salts in refluxing acetonitrile. The complexes exhibit infrared bands for the imine
C=N stretch between 1604–1670 cm-1; around 15–40 cm-1 lower than the free ligands.
The 1H NMR spectra in the CH=N chemical shift region also display shifts (0.1 to 0.8
ppm for the palladium complexes or 0.4 to 0.9 ppm for the platinum complexes) which
are consistent with metallation.
X-ray crystal structures were obtained for eight novel metal complexes, which all
crystallised in the monoclinic crystal system. The solid state analysis shows changes in
the free ligands upon introduction of the metal ions, caused by the coordination process.
Metallation of the free ligands led to twisting of the ligands due to size effects and the
spatial restrictions of the coordination geometry of the central metal ions. The structures
were generally solved by direct methods and refined to R1 = 0.0729 or less. Singlecrystal
X-ray diffraction analysis confirmed that the mononuclear complexes exhibit a
distorted square planar coordination sphere composed of the four donor nitrogen atoms
(two imine and two pyridyl nitrogen atoms) from the Schiff base ligands. The complexes
were generally very stable and differed by the type of metal ion (platinum(II) or
palladium(II)) and the diamine bridging group (2-carbon or 3-carbon linking chain with
various substituted groups). A range of unconventional F···H−C contacts is revealed to
play an important role in the overall bonding and crystal packing of many complexes.
To better understand our measured data and to separate the intrinsic properties of our
molecules from intermolecular interactions, theoretical calculations at the DFT (B3LYP)
level were carried out. These calculations predict the structural and spectroscopic
properties for the free ligands and their metallated counterparts. DFT simulations were
performed for the fifteen synthesised ligands (B3LYP functional, 6-31G** basis set), as
well as three projected ligands that could not be synthesised, and for all proposed thirtysix
metal complexes (B3LYP functional, SDD basis set). DFT simulations were used to
obtain theoretical IR frequency data which was compared to the literature and used to
prove the location of a local minimum energy structure in the geometry optimisation
rather than a transition state. Our results collectively showed the B3LYP level of theory to
be useful in the prediction of IR frequencies for these Schiff base ligands as well as the
platinum(II) and palladium(II) complexes.
Geometry optimisations performed using density functional theory for the free ligands
and metal complexes were compared, where possible, with X-ray data. For the free
ligands the main structural differences were observed for the position of the pyridyl-imine
"arms" of the ligands with relatively good agreement between the two structures for the
bridging groups. On the other hand, the metal complexes showed greater discrepancies
for the bridging groups rather than for the pyridine rings. These differences were also
affected by the length of the carbon bridge; the longer the carbon bridge, the less
variation was observed. The trends in the variation of bond distances and angles with the
metal ion identity and ligand structure delineated by DFT simulations were matched by
similar trends in the X-ray data.
Differences between the gas phase calculated geometries and those determined by Xray
diffraction were attributed to packing effects in the solid state and intermolecular
interactions not being accounted for during DFT computations. The impressive similarity
observed between the structures obtained from X-ray crystallography and computed by
DFT shows the applicability of these computations at the B3LYP level of theory. They
were able to accurately predict structural and spectroscopic properties for the ligands
and complexes presented in this work.
The in vitro cytotoxicities of some of the metal complexes were evaluated against two
mouse cancer cell lines. The compounds tested had lower than expected cytotoxicity
towards the cell lines studied with IC50 values > 100 μM. The interaction of the
complexes with calf thymus DNA has been explored by using absorption studies. From
the observed changes in absorption possible modes of binding to DNA have been
proposed for the metal complexes. Significant changes were observed in the absorption
spectra upon interaction of the complexes with DNA, from which large binding constants
were determined. The changes were, however, not as intense as expected nor were the
spectral variations typical of intercalating drugs. There were also no bathochromic shifts
nor any isobestic points observed for most of the metal complexes, except one. For the
cationic PGM chelates studied, the lack of shift in the wavelength of the visible range
MLCT band maximum and small changes in the band intensity were more indicative of
weak electrostatic interactions. Our spectral data were thus interpreted as being
consistent with non-intercalative binding; either simple electrostatic adduct formation or
major/minor groove binding.
The binding constant values (Kb) of the metal complexes estimated from the titration with
calf thymus DNA monitored by absorption spectroscopy were all in the range of 105 M-1.
This is within the range of those reported for other platinum(II) and palladium(II) metal
complexes that have shown intercalation and/or groove binding. With the lack of
inhibition of growth of the selected cancer cell lines it is possible that the compounds do
not reach nuclear DNA in living cells or that such compounds are possibly substrates for
efflux transporters. All the metal complexes in this work were determined to not be pure
DNA intercalators as had been expected; however, in some cases partial intercalation
cannot be ruled out from the spectral data
Visual Displays in Space Station Culture: An Archaeological Analysis
We offer an archaeological analysis of the visual display of “space heroes” and Orthodox icons in the Russian Zvezda module of the International Space Station (ISS). This study is the first systematic investigation of material culture at a site in space. The ISS has now been continuously inhabited for 20 years. Here, focusing on the period 2000–2014, we use historic imagery from NASA archives to track the changing presence of 78 different items in a single zone. We also explore how ideas about which items are appropriate for display and where to display them originated in earlier Soviet and Russian space stations starting as early as the 1970s. In this way, we identify the emergence and evolution of a particular kind of space station culture with implications for future habitat design
A systematic review and quality assessment of case reports of adverse events for borage (Borago officinalis), coltsfoot (Tussilago farfara) and comfrey (Symphytum officinale).
Symphytum officinale (comfrey), Tussilago farfara (coltsfoot) and Borago officinalis (borage) have long histories of therapeutic use, but their safety has been questioned due to the presence of unsaturated pyrrolizidine alkaloids (PAs). The evidence base underlying these concerns relies in part on case reports. This systematic review assesses these case reports for their reliability to inform this debate.MethodStudy selection was restricted to case reports describing possible pyrrolizidine alkaloid related harm and ingestion of comfrey, coltsfoot or borage. An extensive search of academic databases was conducted. Papers meeting the criteria were critically appraised.ResultsThe search resulted in 11 appropriate case reports, none of which involved borage. Nine reports were assessed for causality and indicated some degree of association between the material ingested and the adverse event. Lack of unequivocal identification of the species ingested compromised attribution and was a significant source of uncertainty. Three levels of identity confusions were found; misidentification or substitution at the level of the whole herb; omission of appropriate botanical identification and attribution of a specific PA to either comfrey or coltsfoot when it is a constituent found in other plants of established toxicity.ConclusionThese cases are an unreliable body of evidence on which to draw conclusions about the safety of the oral consumption of Symphytum officinale and Tussilago farfara. Toxicological studies based on oral ingestion of phytochemically-complex preparations of these herbs may be the most accurate methodology for assessing clinical risk
The differential regulation of Lck kinase phosphorylation sites by CD45 is critical for T cell receptor signaling responses
SummaryThe molecular mechanisms whereby the CD45 tyrosine phosphatase (PTPase) regulates T cell receptor (TCR) signaling responses remain to be elucidated. To investigate this question, we have reconstituted CD45 (encoded by Ptprc)-deficient mice, which display severe defects in thymic development, with five different expression levels of transgenic CD45RO, or with mutant PTPase null or PTPase-low CD45R0. Whereas CD45 PTPase activity was absolutely required for the reconstitution of thymic development, only 3% of wild-type CD45 activity restored T cell numbers and normal cytotoxic T cell responses. Lowering the CD45 expression increased CD4 lineage commitment. Peripheral T cells with very low activity of CD45 phosphatase displayed reduced TCR signaling, whereas intermediate activity caused hyperactivation of CD4+ and CD8+ T cells. These results are explained by a rheostat mechanism whereby CD45 differentially regulates the negatively acting pTyr-505 and positively acting pTyr-394 p56lck tyrosine kinase phosphorylation sites. We propose that high wild-type CD45 expression is necessary to dephosphorylate p56lck pTyr-394, suppressing CD4 T+ cell lineage commitment and hyperactivity
The PhoBR two-component system regulates antibiotic biosynthesis in Serratia in response to phosphate
<p>Abstract</p> <p>Background</p> <p>Secondary metabolism in <it>Serratia </it>sp. ATCC 39006 (<it>Serratia </it>39006) is controlled via a complex network of regulators, including a LuxIR-type (SmaIR) quorum sensing (QS) system. Here we investigate the molecular mechanism by which phosphate limitation controls biosynthesis of two antibiotic secondary metabolites, prodigiosin and carbapenem, in <it>Serratia </it>39006.</p> <p>Results</p> <p>We demonstrate that a mutation in the high affinity phosphate transporter <it>pstSCAB-phoU</it>, believed to mimic low phosphate conditions, causes upregulation of secondary metabolism and QS in <it>Serratia </it>39006, via the PhoBR two-component system. Phosphate limitation also activated secondary metabolism and QS in <it>Serratia </it>39006. In addition, a <it>pstS </it>mutation resulted in upregulation of <it>rap</it>. Rap, a putative SlyA/MarR-family transcriptional regulator, shares similarity with the global regulator RovA (regulator of virulence) from <it>Yersina </it>spp. and is an activator of secondary metabolism in <it>Serratia </it>39006. We demonstrate that expression of <it>rap</it>, <it>pigA-O </it>(encoding the prodigiosin biosynthetic operon) and <it>smaI </it>are controlled via PhoBR in <it>Serratia </it>39006.</p> <p>Conclusion</p> <p>Phosphate limitation regulates secondary metabolism in <it>Serratia </it>39006 via multiple inter-linked pathways, incorporating transcriptional control mediated by three important global regulators, PhoB, SmaR and Rap.</p
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Revision in the first steps of the biosynthesis of the red antibiotic prodigiosin: use of a synthetic thioester to validate a new intermediate.
Funder: Frances and Augustus Newman FoundationFunder: Emmanuel College, University of CambridgeFunder: Cambridge Commonwealth TrustA biosynthetic pathway for the red-antibiotic, prodigiosin, was proposed over a decade ago but not all the suggested intermediates could be detected experimentally. Here we show that a thioester that was not originally included in the pathway is an intermediate. In addition, the enzyme PigE was originally described as a transaminase but we present evidence that it also catalyses the reduction of the thioester intermediate to its aldehyde substrate
Quorum Sensing Controls Adaptive Immunity through the Regulation of Multiple CRISPR-Cas Systems
Bacteria commonly exist in high cell density populations, making them prone to viral predation and horizontal gene transfer (HGT) through transformation and conjugation. To combat these invaders, bacteria possess an arsenal of defenses, such as CRISPR-Cas adaptive immunity. Many bacterial populations coordinate their behavior as cell density increases, using quorum sensing (QS) signaling. In this study, we demonstrate that QS regulation results in increased expression of the type I-E, I-F, and III-A CRISPR-Cas systems in cells in high-density populations. Strains unable to communicate via QS were less effective at defending against invaders targeted by any of the three CRISPR-Cas systems. Additionally, the acquisition of immunity by the type I-E and I-F systems was impaired in the absence of QS signaling. We propose that bacteria can use chemical communication to modulate the balance between community-level defense requirements in high cell density populations and host fitness costs of basal CRISPR-Cas activity.This work was supported by a Rutherford Discovery Fellowship (P.C.F.) from the Royal Society of New Zealand (RSNZ) and the Marsden Fund, RSNZ. A.G.P. was supported by a University of Otago Doctoral Scholarship. G.P.C.S. is funded by the Biotechnology and Biological Sciences Research Council, UK
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